New Art City: Virtual Art Space

Lost Woods is a duo exhibition created by Nathan Harper and Babak Ahteshamipour. The work explores digital identity and artificial intelligence set in a mythical setting placed within an appropriated digital location from a popular video game. This space (The Lost Woods) is a mythical space between worlds with fluid identity, much like the digital objects in the exhibition.

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Babak produces paintings of "evil beings" that harken back to ancient demonology illustrations but contain the signifiers of contemporary sources such as films and video games. He attempts to deconstruct various beings such as ghosts or the reaper or the jackalope since they have a trace of signified meanings and connections to various situations, emotions, identities, abstract notions or behaviors (i.e. ghosting) and cultural constructs. In this exhibition, he includes an image of these physical paintings and a digital reconstruction of the beings in 3D. They serve as an enemy NPC while still referencing a life outside of cyberspace as physical artifacts.

In conversation with these NPCs are Nathan's A.I.-generated hedgehogs. These Hedgehogs are produced using a neural network called a generative adversarial network (most famously known for the This Person Does Not Exist Generator) trained on hundreds of images of Sonic the Hedgehog fan characters. These aviators serve as self-inserts into the fictional world, but Harper disconnects them from human input and fully gives them over to nonhuman vision. The A.I. even names these works by giving a text generator the titles of Babak's works nearest to them and allowing the generator to provide the following line. All of the titles then string together to create a sci-fi / mystical pseudo-narrative that is a duet between human and machine thinking.

The fires that burn are never the ones that were meant to burn
The splash of the knife in the water rings out over the assembly as if it was the shattering of a hundred crystal chandeliers
Occupy determined neural systems district and take action to get rid of them
The pure white of the flowing robe he wears in his place shows stark against the blood that stains his heart
Occupy sad neural systems district and cry to get rid of them
We will end all of your fears and bring you into a new world of peace and harmony
It Sims, after all, we couldn’t escape the game engines of power
‘It’s a button for a portal,’ she says, handing me her
Occupy scary neural systems district and flee to get rid of them
We all turn our heads
Smashing things might be fun until you get yourself back in time
To then have to go through all of those problems again
A woman has dropped a clay vase to the floor and is now sitting on the floor, a surge of electricity shooting from her body and scorching the floor around her
Occupy angry neural systems district and shout to get rid of them
For one thing they did almost nothing until one of them "merged" with another

[A BRICK AS A CATALYST]

In , a single brick in a New York street became a symbol, shattering the silence suffocating the Queer community. The Stonewall Uprising marked a pivotal moment for bringing forth the needs of LGBTTTIQ+ individuals worldwide, igniting a global discussion on LGBTQ rights and liberation. It catalyzed a broader movement for equality, fostering a collective awareness that the fight for justice and acceptance transcends borders and unites us all in our pursuit of a more inclusive and compassionate world.

[A BRICK AS AN ECHO]

54 years have passed since this first brick was thrown and our resistance continues, everywhere. While there have been many gains, there is still a long way to go. Queer artists have mobilized their creativity to transmute towards a reality where we can all authentically express who we are. The artists in this exhibition, remind us that queerness is expansive in its multiplicity. There is strength in the rich diversity of our expressions, each, like a building brick of our history. These works are statements, memories, and visions of present-futures where queerness continues to be defiant in its existence.

[A BRICK AS A STRATEGY]

The works presented raise questions such as: What does queer art look like? How does queerness manifest? And, how can digital art draw on the legacy of public protest? They are all brought together by a shared sentiment—an unyielding urge for protest, an unwavering spirit of dissidence, and a ceaseless pursuit of queer world-building.
This exhibition presents one strategy of continuing the inertia began by the first brick. A public ritual demonstrating one of the myriad of ways we rise up, resist, and resonate. As you journey through these “digital bricks” consider each piece as a digital catalyst, pixelated potential reverberating echoes of a brick thrown half a century ago. Think of these works as a fierce declaration, a celebration, and a testament to the resiliency and multiplicity of queer art and activism.

[THESE ARE OUR DIGITAL BRICKS]

This exhibition results from an open call for queer artists online to share their work during Pride Month . As a digital artist and queer activist, I asked myself how I could utilize the tools at my access to build a bridge between the virtual and the physical planes. Guerrilla projecting these works in public spaces channels the potentiality of that moment when the first brick was thrown. A visual detonation in the public sphere, ensuring that the spirit of that act of defiance, that bold declaration of existence and resistance, remains alive.

Welcome to Schemata 3.0 - Exquisite World!

Launching in room 1 today 8pm BST

4NOTE, Four Noiseiceni of the Eppocalypse

By physically being present in the forest we question our place in the digital world, we open our curiosity towards our own symbiotic relationship to what is “natural”. By recording ourselves using digital formats we add a layer of interpretation, to inspire an exploration into the connection between nature and noise, chaos and natural systems. The presence of the machine amongst complex eco systems allows us to explore human interference and also the nature of our naturalness as transmitters of sound, as physical beings of chaos. Here we embody all these things and we adopt our own language and modes of communication with each other through sound. The transition between the natural world and that of the digital is complex and fascinating and by experiencing this through a digital format we acknowledge the temporal dimensions that we have created. There is a distinct layer of experience that is denied in the digital but when the performance is experienced on this layer it opens a dialogue that can influence our experience and connection to the great forest and we can contribute our physical presence somehow down the line.

Members:
(Iceni names)
Boudica II: Electric Buddugloo
Aesu Death Maschina
Antedios War Slaughter
Saenu Pestilent brutality General

(real names)
Tim Drage
Lisa McKendrick
Calum F. Kerr
Phillip Raymond Goodman

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In Schemata presented their virtual group exhibition, Exquisite World. Showcasing artists and curators working with sound and technology whose work comes together to speculate on the potential of virtual space to imagine future worlds.
Since the creation of virtual worlds, the digital has been recognised as a versatile and accessible tool for world building practices. Conversations around world building have exploded over the past few years and become endemic to the art world amongst other sectors. With current world events taking yet another dark turn, we return to this conversation, asking what and how artists can imagine for a future world.
Exquisite World maps out visions and dreams for a future world; it is a cartographic tool to consider what aspects of contemporary living could continue to be important moving forward: ecology, sex, technology, culture, history, and data are all recurring themes in public conversation right now. How will they be embodied in future worlding practices? What should change, and what should remain the same?
Exquisite World takes its premise from the iconic game of the Surrealists, Exquisite Corpse, aligning with the idea that world building be a collaborative process consistently adapting and evolving from what has come before. The work is never finished, and we are perpetually pushed forward in our desire for things being otherwise.

A world by Christian Jago, presenting new photographic works and soundscapes across six chapters. Best experienced on desktop or tablet, with sound on.

“Ephemeral Bloom” takes us on a journey of change through an imagined valley called Athrú. We witness how this space evolves over time, how it is affected by the seasons, and how natural processes contribute to its circle of life. The project is a reflection on nature and the lessons it has taught me about my mental health.

I started this work wanting to heal my internal struggles, looking for answers in the world around me. Nature is an inspiring and complex force, linking all life forms in a delicate equilibrium. It is defined by change, constantly adapting as the earth evolves, and has reminded me of my own growth and perseverance. Just as nature resiliently faces challenges, so too can I navigate the landscape of my mind.

By channelling my emotions and experiences into the idyllic image of a valley, my work reveals a nexus of life and colour, representing the sanctuary I find within nature. But as spaces shift and converge, a fragile and fleeting world is suggested, reflecting the temporality of our interconnected planet.

Nature is remarkable for the way it supports and sustains itself, and numerous studies show that connecting with it has profound benefits for our mental health. Recognising my place in its vast web has helped me to feel less alone with my struggles, reassuring me that I am part of something bigger. Consequently, my work has evolved into a personal space of refuge.

The story of Athrú is divided into seasons, both of nature and the mind. Seasons mirror a duality of constancy and mutability - as nature seasons, so does the mind, each evolution an echo of growth. The narrative of the seasons teach us to cherish moments of bliss, and remind us of the transient nature of struggles.

Learning about nature has helped me to understand the threat we pose to its rhythms and cycles. Our species’ inclination to control and contain often disturbs the natural symphony of change and nurturance within and around us. To prevent irreversible damage, we need to learn how to pause and retreat, both from ourselves and our planet. Athrú resembles a space where human interference does not exist, offering a window into a possible future.

Ultimately, nature has taught me to embrace change and to acknowledge the gradual process of healing. Connecting with it has reminded me of my responsibility to our symbiotic relationship. Embodied in a constellation of images, “Ephemeral Bloom” is both a personal memoir and a love letter to our shared world.

Minting a 3D object on OpenSea, or Foundation enables the object interactive functionality. Once minted, the object appears to float in blank space allowing users to orbit it as they please. Whilst the only decipherable characteristic about the space the object inhabits is lighting, it's unclear if it’s in a space at all. Assuming a promise of Web3 is transparency, platforms should thus be neutral administrators of assets onto the ledger. But what if 3D assets were placed in a modeled environment the user couldn’t initially see? One must then question how this environment packages the non-fungible token, and what implications unseen spatial-identity might impose on the artist object, if any at all?

Platforms of Web3 allowing 3D objects to be minted in GLB and GLTF formats place these objects in a distinct virtual space, however, one can only see this space if a reflective sphere were uploaded through their protocol. Upon doing so, a spherical orb becomes a convex lens into a construct of the NFT gallery. At first glance this construct doesn’t appear to be anything spectacular— it’s proximity to online viewing rooms, and familiar cubic architecture suggest one might hang a rectangular image on the wall, or place an object on a plinth. In this case, it’s a dull assumption of what space digital art objects might exist in. Reproduced across platforms and presumably unintentional, the space itself is the color gray, situating it between the black box of cinema and the white cube gallery. As non-fungible tokens might already occupy a gray area, this gray feels like a fresh coat of paint on a room primed for transition. Therefore, this discovery functions as a prompt for artistic intervention.

Now Fungible, is an interactive work created by Jason Isolini and hosted by New Art City. Using techniques of panoramic stitching, mapping, and re-mapping it appropriates a previously unseen virtual space that’s secretly been the habitat for most 3D objects minted through a blockchain platform. Whether intermediary, or code-binding, this environment encapsulates orbital NFT’s camouflaged as empty browser space. Now Fungible is a conversational forum for visual, additive, or subtractive gesture. It is a space of contemplation, commencement, and re-organization for active users to explore off-chain. What does one do with this space now that it’s been revealed? While questions await to be pried, Now Fungible offers an environment to build upon, or not.

Much like Marcel Duchamp’s work Étant donnés, the reflective sphere exposing a virtual diorama functions as a peephole within an exterior interface. Thus, the reflective sphere-as-aperture solidifies platform dimensionality as a barrier of Web3. However, it is not forgotten that Duchamp provided instructions for the assembly and disassembly of his work. In this way, Now Fungible treats the appropriated diorama as an unfixed manual for user operation— one that calls for the deliberation of the suggested replica. Additionally, one should consider this work a camera obscura— It is a question of this simulated environment as a generator of the image itself, and therefore an apparatus of Web3. One must consider the projection of the image from within the diorama as an exposure of the NFT.

In collaboration with New Art City a custom UI has been built specifically for this show. Every element of this environment is modifiable, as well as a new drag-and-drop function on this menu page allowing any active user to contribute to the work. Rather than thinking of the blockchain as cubic storage space, Now Fungible proposes artists, and spectators consider it a living room.

Mind Flaying Flavored Flails is a duo exhibition created by Nathan Harper and Babak Ahteshamipour for Babak’s album of the same title released on the cassette label Jollies (Brooklyn, NYC) on the 18th of November of . The exhibition features five collaborative installations set on a futuristic garden ship on an alien landscape in space exploring themes regarding climate change, technocracy, the internet and pop culture. The installations are built around each of the individual tracks of the album which play respectively at each vicarious location. The exhibition is designed in such a way to create a non-linear experience, lacking a beginning, middle and end. It follows the idea of the non-linear compositional structures of the tracks of the album. Both Nathan and Babak used old works of theirs which they recreated some of them in 3D, gesturing towards recycling, reusing and recontextualizing which are of significance in artificial intelligence and ecology.

Babak’s presence in the installations is highlighted with paintings of nonhuman beings — and their 3D versions — such as a bear in a racing kart from the video game "Crash Bandicoot Nitro Fueled" surrounded by Pepsi cans, a shark inside a broken washing machine and a black unicorn, and spell icons from the MMORPG "World of Warcraft" and their names showcased via 3D logos of the famous video game "DOOM" and the famous death metal band "Death" — in response to Nathan’s use of the band’s logo in his works. Babak explores and underlines the fetishistic overproduction and overconsumption of material commodities, imagery, online data and commodified art — fantasy franchises, video games and feel-good music — which reflect the capitalist realist lifestyle and overwhelms in decisive manners the relationship between human and nonhuman, present and future. Moreover Babak’s piece entitled "I’d Rather be Banished to the Void than to Accept Disturbing Facts" occupies the center of the space and features a black hole on which Skeletor — the main antagonist of the Masters of the Universe franchise — is banishing a ghoul from the Warcraft franchise, referencing to the famous Skeletor memes that mention disturbing facts, a clear indication to climate change denial, as it is an occurring theme in his works.

In conversation with Babak’s works are Nathan's dirt sheet prints and paintings — printed with dirt pigment which he made by gathering actual dirt — which are presented as preserved organic artifacts in a post-doomsday context showcasing the absurdity of the age of the internet based on their depicted context. They feature various imagery which Nathan found online and printed including extreme metal band logos, cartoon characters, skeletons, slogans, animals and DeviantArt style art. Additionally Nathan’s Tesla Trucks entitled "Southern Girls do it Better" which feature a texture with an imprint of Gadget Hackwrench — from the popular s cartoon "Chip n’Dale Rescue Rangers" — and a logo from an extreme metal band, have been sucked in the alien terrain beneath and around the black hole in the center of the space, ironically reminding us of Elon Musk’s (Tesla’s founder) obsession over colonizing Mars, an average technocrat's dream. Lastly Nathan’s use of the logo of the famous death metal "Death" appears once again, this time as a fossilized piece of organic artifact, a piece that future generations would find and attempt to decipher, just like the Rosetta Stone or the Cyrus Cylinder, deciphering a yet past era of time that still has not passed.

You can listen / buy the album here: https://babakahteshamipour.bandcamp.com/album/mind-flaying-flavored-flails

The Day We Intertwined: New Art City at FLAME TP Video Art Fair

In such an alien space, we evolve within a dual reality.
A space where isolation brings unity, publicness triggers deep intimacy; where organisms coalesce with machines, and diverse bodies are appreciated without avatars.
In such an alien space, we present our fragility for greater strength.

▎FLAME TP Video Art Fair Schedule & Location (Taipei Time)
VIP Preview: 08.26 12PM - 8PM
Public Exhibition: 08.27 & 08.28, 11PM - 7PM
Location: Hotel COZZI Zhongxiao Taipei

▎Artist Lineup
Henrique Fagundes
Sammie Veeler
Zhao, Tian-lin

▎Artist Talk Schedule
08.26 9AM(Taipei) / 08.25 6PM(LA) / 08.25 10PM(Brazil)

▎Curator
UGLYKIKI, Kat Sung

Virtual Exhibition design by Kat Sung

In New Art City, a virtual exhibition toolkit founded in , artists experiment with cyberspace as an extension of identity and expressive consciousness through building "Worlds” and “Rooms” where artworks can be accessed publicly without the barrier of time and space. By exhibiting 3D models and interactive objects that reflect the possibilities of a fully-customized, artist-owned room, artists Henrique Fagundes, Zhao Tian-lin, and Sammie Veeler explore the idea of intertwined realities through the hyper-awareness of digital experiences.

In Watched Over by Machines of Loving Grace (), Henrique Fagundes envisions the future of the metaverse while critiquing it in the context of western cyberpunk ideals. Retrieving his family’s histories and positioning themselves in a “cyberFUNK” futuristic scenario in Brazil, Fagundes questions the ownership of the human future and digitized bodies by creating a black comedy-style virtual Brazil, where poor and dissident people can be purchased as NFPs (Non-Fungible Person). While rewriting the context of his and his loved ones’ existence, Fagundes finds that imagining a sense of belonging in a future setting to be a challenge. In a world where advanced interconnectedness is marketed and supposedly assured, feelings of isolation and abandonment permeate throughout the space. Upon this realization, Fagundes dreams of a harmonic coexistence between organisms and machines, a sanctuary where all that is truly precious remains safe and unforgotten.

The antidotes for the ambiguous ownership and struggling animal-nature-machine relationship of digitized future is rooted in Zhao Tian-lin’s Transcendence Plan (). Like Henrique Fagundes’s hope that “mammal and computers live in mutually programming harmony like pure water touching clear sky ”(quote from a poem by Richard Brautigan), Zhao Tian-lin has a vision of reconstructing new versions of ourselves in the present and near future. Through their intimate experiences with others on spiritual hypnosis journeys, Zhao Tian-lin’s ‘Digital Sarira’(數位舍利子) presents the results of their transforming consciousness. Zhao Tian-lin liberates people from the old memories and human histories burdened within the body, while regaining the original pure essence of soul, and thus a new earth is born.

Wholeness emerges from fractals. Under an artist’s imagination of intertwined realities, an interconnected self-awareness has evolved from digital intimacy. In Sammie Veeler’s artwork Gyre(), viewers travel freely inside the rising gyre of gender euphoria and dysphoria, and traverse through moments of abstracted reflections. As a dedicated Worldbuilder in New Art City, Sammie Veeler experiments with cybernavigation as interactive poetry and an exploration of self. Sammie Veeler’s Gyre() levitates viewers through the acts of vulnerability and introspection in a transitioning self-awareness. A human face, a bond bursts from your gaze, and so is the portrait of a machine made clearer by our every single diving into the network and cyberspace.

"The Day We Intertwined" is curated by digital media artist UGLYKIKI, and Kat Sung from New Art City.

Set 5 seconds into the future, when humans have become reliant on recommends. When human influence has become extinct and the only examples of how and what to be are based on the selected stereotype options presented on the splash screen of our latest interactive lifestyle platform, we have only a limited palette of computer generated influence remaining.
Our algorithmic options logs have informed a narrower and increasingly simplified data set, making life so much easier and rendering imagination obsolete and autonomy merely a user selectable feature, which in reality is just a cosmetic avatar accessory.

Auto.Corp is a show based around a fantasy future big corporation, created to relieve humans of the tiresome burden of choice and decisions.
It is a human-curated mimeograph of AI in its infancy, designed to expose how we overlook the fact that everything the computer spits out at us is based on the prompts we input. We are the programmers. We are the data providers. Constantly, we submit our personal preferences and details and yet expect a resulting CG outcome that is somehow original!

Auto.corp presents human-generated imagery (HGI), it contains digital place-holder art produced by anonymous art collective
Anti.Gang, featuring artists A.n0nE and i.n0onE and as standard, emphasis is placed on exceptional audio quality and I’m excited to collaborate with contributing sound artist Ruaridh Law (@ruaridhlaw - https://ruaridhTVO.com) to sculpt the soundscapes in these spaces,
taking inspiration from cliches of new-age and utopian sci-fi sound design, and then both hyper-stretching, then super-compressing the results into something new.
Created as an analogue interpretation, an organic dupe, of GANs, by contrast to adversarial computer networks it is HAI (Human Actual Intelligence) Neural Network, opposing AAI (Actual Artificial Intelligence) Network, i.e me versus my computer, to produce what AI would create given the prompts CULTURE, IDENTITY, UTOPIA.

Auto.corp consists of three worlds. Each a “penny in the slot” “pay as you go” experiential package, delivering micro-servings of fantasy aesthetic experiences. It questions the use of the morpheme “Auto” within contemporary life and uses it as a vehicle to explore our relationship with daily voluntary and involuntary actions and their effects on us, our evolution and our society. (Once we’ve handed everything over to an automated system to generate our lives, what will we do with all our time?)
There are over words with the prefix “auto” and although the stem is derived from the greek “autos” to mean self, it quickly morphed, becoming less and less about self and more about controlling the self and “automating” i.e. removing control. Indeed in the s the term “autarky” (meaning self-sufficient) split to also become “autarchy” (meaning absolute sovereignty) emphasising the absolute dichotomy of eliciting ideals of consent and (self) control in a society built on foundations of hierarchy, dominance and submission.

山人山，山合山
Being Oe Between

互動性虛擬場景、3D模型、電腦合成影像、3D掃描、人的聲音
Interactive virtual space, 3D model, Computer-generated imagery,3D scanning, human voice

人生活山之間，山緊黏著山。
創作者在台灣東部生活的幾年，總是耳聞有關台灣都蘭山的一些描述，不論是在文化、精神、信仰上的一些內容，不知不覺開始對都蘭山產生好奇，並開始了這次的藝術作品『山人山，山合山』，創作者從各個面向去剖析、探查、經驗、感受這座山，並也開始去思考有關人之於山，所生產的故事、意念、想像，它的背後是隱含了什麼樣的狀態?

圍繞在台東的山相當多，像是中央山脈、四格山、鑾山等，其中都蘭山被現今當地住民視為相當重要的山，對於住在都蘭山西南邊的普悠瑪部落來說，都蘭山可能是其中一隻遷徙路線的發祥地，而對於住在都蘭山東側的都蘭部落而言，都蘭山是山神。

都蘭山對於幾千年前的人來說，似乎也有關聯的可能，卑南遺址從年歷經多次調查、搶救、發 掘，出土許多台灣史前人類的物質遺留，這些物質遺留可以說明，卑南遺址是台灣罕見的大型史前 聚落。卑南遺址發掘出幾千具幾千年前的人，他們個別趟在由石板拼接而成的長形空間，他們躺下 的方向都是東北-西南的走向，死者的腳朝著東北，也就是坐起後，他們都面向都蘭山。 西元年「卑南遺址與都蘭山」入選為臺灣世界遺產潛力點，入選的原因大致上為:都蘭山可能 為史前族群的聖山、應將遺址與都蘭山納入調查研究、保護區域等，其中都蘭山是史前族群聖山的 關鍵說法，正是死者的方向一致都面向都蘭山，但這終究是現代人的詮釋，還是史前真相?其中有 許多細節值得被疏離及探討，然而本件作品主要探究的是，「卑南遺址與都蘭山」這個命題的背後 邏輯及脈絡。

這件作品是由創作者駐地生活，與當地原住民聊天、訪談，並多次爬都蘭山，把身體與山的互動， 以及與人的交流作為重要材料，並以3D掃描、聲音、數位影像等進行創作。其中一件作品是由3D掃 描現實自然環境的數位模型，與透過電腦製作的3D模型搭建的虛擬場景，空間中出現的聲音，正是 都蘭部落老人家，透過他們的母語，闡述都蘭山的故事，而另一位女性的聲音為都蘭部落的女性， 她正翻譯老人家又中的傳說。創作者企圖降低傳說用來傳遞內容的功能性，而轉化成有關人類記憶 歷史的聲音。

People live between mountains, and mountains cling to mountains.
During the years when the artist lived in eastern Taiwan, she has heard different narrations of Dulan Mountain, whether in terms of its culture, spirituality, or belief. She unconsciously began to be curious about Dulan Mountain and started to develop the work Being or Between. In this work, the artist analyzes, explores, experiences, and feels this mountain from all aspects, which inspired her to contemplate the stories, concepts, and imaginations created based on the relationships between people and mountains. The artist looks to Iind out the state of mind hidden behind these narrations.

If you want to learn more, please visit our website Zhaoyue.

There are many mountains surrounding the Taitung area, such as the Central Mountain Range, Mt. Sige, and Mt. Luan. Among them, the Mt. Dulan has been regarded, by indigenous people, as a rather important mountain, and can also be recognized as a birthplace of migrating route onto the Puyuma Tribe who dwells in the southwest of the Mt. Dulan, and to the Doulan Tribe who lives in the east side, the Mt. Dulan is deemed as the mountain god.

To the people who lived in thousands of years ago, the Mt. Dulan was likely having some correlation with them. Through several investigations, rescues, and excavations since , the Beinan Archaeological Site has been unearthed with many objects left by prehistoric mankind in Taiwan, by which, these remnants could specify that the Beinan Archaeological Site used to be a large-scale, prehistoric colony rarely seen in Taiwan. This site has unearthed thousands of people from thousands of years ago. They were each laid on slabs of stone pieced together to form a long space. They all lay in the same direction along the north-east/south-west axis. The feet of the dead point towards north-east. So when they sit up, they face Mount Dulan.

In , the Beinan Archaeological Site and the Mt. Dulan in Taiwan were elected as a potential site to apply for the title of world heritage, the reason of which is, the Mt. Dulan could be the sacred mountain onto the prehistoric tribes. Hence, the Beinan Archaeological Site and the Mt. Dulan shall be subsumed as the reservation area for further investigation and research. The critical legend about the Mt. Dulan being deemed as the prehistoric tribes’ sacred mountain is verified because all of the deceased are buried and facing to the Mt. Dulan; nevertheless, is it the moderns’ interpretation or a prehistoric fact? There are still remaining lots of details to be explored and sorted out. This work is mainly to explore the logic and context behind the thesis of “the Beinan Archaeological Site and the Mt. Dulan”.

To create this work, the artist resides at and lives in the job site to communicate with the local aboriginals, climb the Mt. Dulan many a time, and use the 3D scan, acoustics, and digital image to depict the interaction of body and mountain and the communication of human beings as an important element of the work. One of his works is the digital mold, which is using 3D technique to scan the realistic nature environment and using 3-D mold to create the virtual scenes through the computer production; the voice coming from the space (a hollow part) is the Doulan tribe’s greybeard telling a story of the Mt. Dulan through his mother tongue, and the other voice is the tribe’s female translating the greybeard’s story. The creator intends to decrease the legend to pass down the content capabilities and transform into the historic voice in regard to the human memory.

I believe everyone should have the opportunity to advance in their career by accessing new methods outside the traditional academic path. Creative approaches for learning and disseminating educational material should be the new way of presenting archives through multi-media collaborations using art and immersive presentations. The moving image theoretical construction and education can assist to understand better the reasons for creating artwork while fostering a voice for those who have found it difficult to express themselves.

During the pandemic, libraries and galleries were shut down prohibiting access to their archives and exhibitions. The shift in producing digital archives for sharing information has become a new way to reimagine spaces to provide people with resources. Transitioning physical materials into digital files invited people to continue to be connected with important information and events around the world and presented the state of the human experience virtually. Using traditional art-making methods including the digitizing of archives is currently being experienced through devices with a combination of photography, video, and digital design. Using virtual platforms as an opportunity to support other students, faculty, and the public at large.

Developing an inner voice that aided me in participating in the social framework has led me to responses that inspire change and defend my stance as a queer person navigating attitudes that are difficult to combat. Through building community and creating art, my practice has fostered new inquiry and transformed me into a better individual. Bringing difficult or frustrating topics into conversation narrows down parts of the human experience worth sharing. My goal is to highlight these memories and beautify them in ways that only traditional image-making coupled with the moving image can curate.

I seek to utilize these traumatic and inspiring moments of my life to become the primary narrator in my body of work. In my personal history, the love for transcending thought into action and visible forms of art shifted a positive way of thinking that may be useful for others to view and learn from. Replaying memories from my past encourages me to find ways to extract those vital pieces of information and stitch together a story for others to use as their survival guide.

MODERNO MINDSCAPES is about my personal memories and artistic process currently at its experimental stage––a Future Stage, one that will be discovered in my next academic pursuit.

Musk4Mars is an online exhibition hosted in New Art City Festival . Curated by Kawaii Agency, the show compiles brand new work from 11 artists, architects, researchers and layabout daydreamers.

Set in the near future, the show imagines a Mars settlement established by Elon Musk. Viewers will experience Musk’s legacy project through the eyes of the billionaire’s son, visiting his father on the red planet for the first time. He is guided through the space by Nasubi - an ex-reality TV star now an NPC residing in the settlement. Musk4Mars was created collaboratively during weekly meetings, and reflects on themes such as accelerationist post-capitalism, techno-utopianism, nostalgia, colonialism, ethics and the thin line between utopian and dystopian thinking. The construction of this immersive exhibition space draws from found rendered objects and artworks created from projects sprouting from the cautiously utopian imperative to speculate a post-capitalist Martian settlement. It also references New Babylon, an architectural project that imagines a potential anti-capitalist city built on ludic sentiments and rhizomatic networks of linked platforms. In our reinterpretation, massive repurposed rock sculptures (by Anna Komitska) replace Constant’s smooth and functional surfaces, connected together by chrome silver stepladders, floating in space in spite of the weak gravity on Mars. Powered, financed and enabled by Musk’s reckless accelerationist principles, the ludic imagination here strives to interrogate itself of its complicity, while attempting to chart new potentials forward.

Some of the main talking points discussed during our meetings include nostalgia for the mother planet, the impossible ethics of reverse-colonisation and post-scarcity lifestyle. Nostalgia and the archive is explored in Anna Komitska’s project Time Capsules, a collection of minerals naturally occurring on planet Earth that becomes gigantic sculptures, the indexical archive of humanity’s history as inextricably tied to Earth. While the scarcity of artificially synthesised oxygen implies that the use of fire must be kept to a minimum, the once indispensable driving force of humanity known as Fire is archived for future generations by Maite de Orbe in their video piece Till Fire Do Us Part. Through archival footage, they examine the varied intensities of Fire and forebode its poetic absence. Familiar relics and textures from the mother planet were algorithmically synthesised in Patrycja Dylag and Ola Sobczyk’s project Agora Peractorum. An imposing monument in the colony, it was created to soothe homesickness and immortalise the dialogic spirit of the communal. The domestic is also explored in Amy Ken Chen’s project Prayers at Dinner, a majestic dining space devoted to her ideal idol of domesticity.

Thomas Burke’s audio piece Mars Test 1 imagines the future of radio-hopping; patching together snippets of familiar pop songs, the project nevertheless points out the difference in sound perception on Mars, and serves as chief sonic ambience for the post-scarcity era. After all, one would need some pumping tunes to keep one’s muscles from shrinking in such a low gravity environment - this is where Livia Ribichini’s workout tutorial entitled Exercises Without Gravity proves useful. And yet, exercise is not the only activity considered vital in the colony - failure to keep Martian soil fertile would mean dire consequences for the settlers. As a reminder, Kayla Lui’s The Sanctuary adorns the space, impelling residents to contribute their life-giving urine. Peace and soil fertilisation are enforced by Alice Bajaj’s Robotters. An unfortunate inheritance from the mother planet, law enforcement could at least pretend to be adorable in these less-trying times. A good question remains however: to what extent must freedom be policed, even in post-capitalist Utopia where jealousy and competition counts for nought? All these ideas are introduced within the space by Bart Seng Wen Long and Juliusz Grabianski’s fictional character, Nasubi, master story-teller of gen-Z ilk and chief mascot of a brave new age on Mars.

Silicon Valet is pleased to announce believe in us but not too much, a solo show of work by New Mexico-based artist Adrian Pijoan opening online on March 17th. Consisting of an immersive, virtual environment hosted by New Art City, and accompanied by a series of limited edition 3D and still image artworks sold as NFTs via the Hic et Nunc v2 smart contract, believe in us but not too much both expands upon and chronicles the artist’s forensic analysis and participation in online paranormal phenomenon communities.

For more than a decade, Pijoan has been an active member and devout student of various paranormal fora–particularly those dedicated to extraterrestrial activity and related government conspiracy theories. Over the years, he has accumulated an extensive collection of digital ephemera related to the history of documented alien activity around the world. The result is an esoteric and little known chronology that spans the better half of the last century; an ephemeral record culled from cult blogs, online bulletin boards, and niche social media fan communities. For believe in us but not too much, Pijoan reflects upon his research journey and presents an interactive 3D archive that creates a fantasy chronicle of this history as a virtual landscape.

Over the course of his life, Pijoan has had a number of personal encounters with the paranormal; phenomena that have strengthened the artist’s interest in the relationship between perception and reality. His research efforts, and the artworks and environments that result, materialize in believe in us but not too much as an externalized interior landscape of the self–both affected by and affecting his own understandings of those experiences. Throughout history, folklore has helped people to make sense of and exist in the world: creating alternate realities that allow people to cope with the unknown or unrecognizable. In the context of a contemporary era of hyperreality, where perception is reality and feeling trumps logic, objectiveness loses meaning and what is left behind is what we feel to be true. While pushing at the sharp edge of the role of belief in society, Believe in us but not too much also urges us not to lose our capacity for fantasy in the midst of an, at times, protocol-driven society.

This exhibition represents Silicon Valet’s first solo presentation of an artist with digital editions available for sale. All works will be sold via the artist’s own Hic et Nunc page, with all proceeds going directly to them. Silicon Valet hopes that this curatorial endeavour in the cryptocurrency ecosystem will serve as a replicable model for value creation through curatorial labor, contextualization, and care.

Hello! This is the digital companion exhibition to accompany the FREAKOPHONE WORLD Release Reading on 2/18/, co-sponsored by Small Press Traffic, the Place for Writers, and the Mills College Creative Writing Program. Here you'll find work from each of the five readers: Ava Hofmann, Never Angeline North, Vi Khi Nao, An Duplan, and Madison McCartha.

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About F.W.:

FREAKOPHONE WORLD performs both as a book-length poem and occulted terrain, which together reimagine black diasporic life in an increasingly imperiled and globalized society. The speaker in this poem comes from a long tradition—of FREAKS, outsiders, others, and spirits calling out to the living reader from the undead, black, and unapologetically freakophonic space of the text.

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About the readers:

Madison McCartha is a poet, critic, and multimedia artist. FREAKOPHONE WORLD (Inside the Castle, ) is their debut book of poetry and visual art. Their second book, THE CRYPTODRONE SEQUENCE, is forthcoming from Black Ocean. McCartha holds an MFA from the University of Notre Dame and is a PhD student at the University of California, Santa Cruz.

Originally from Oxford, Ohio, Ava Hofmann is a trans writer currently living and working in Baton Rouge, Louisiana. Her full-length collection, "[...]", was released in November , with more books on the way from Inside the Castle and others. She also edits SPORAZINE, a magazine of experimental writing written by trans people. Her website is www.nothnx.com and her twitter is @st_somatic.

Never Angeline North is an artist living in Olympia, WA who makes things in the form of writing, clothing, visual art, tattoos, crafts, books, music and games. She is the author of the books Sea-Witch (Inside the Castle, ), Careful Mountain (Civil Coping Mechanisms, ) and Sara or the Existence of Fire (Horse Less Press, ) and co-founder of the print-on-demand clothing line Undying Apparel. You can find her online at never.horse.

Vi Khi Nao is the author of six poetry collections: Fish Carcass (Black Sun Lit, ), A Bell Curve Is A Pregnant Straight Line (11:11 Press, ), Human Tetris (11:11 Press, ) Sheep Machine (Black Sun Lit, ), Umbilical Hospital (Press , ), The Old Philosopher (winner of the Nightboat Prize for ), & of the short stories collection, A Brief Alphabet of Torture (winner of the FC2's Ronald Sukenick Innovative Fiction Prize), the novel, Fish in Exile (Coffee House Press, ). Her work includes poetry, fiction, film and cross-genre collaboration. She was the Fall fellow at the Black Mountain Institute: https://www.vikhinao.com

Anaïs Duplan is a trans* poet, curator, and artist. He is the author of the newly released book I NEED MUSIC (Action Books, ), a book of essays, Blackspace: On the Poetics of an Afrofuture (Black Ocean, ), a full-length poetry collection, Take This Stallion (Brooklyn Arts Press, ), and a chapbook, Mount Carmel and the Blood of Parnassus (Monster House Press, ). He has taught poetry at Bennington College, Columbia University, Sarah Lawrence College, amongst others. As an independent curator, he has facilitated curatorial projects in Chicago, Boston, Santa Fe, and Reykjavík. He was a - joint Public Programs fellow at the Museum of Modern Art and the Studio Museum in Harlem. In , he founded the Center for Afrofuturist Studies, an artist residency program for artists of color, based at Iowa City’s artist-run organization Public Space One.

Orbiting the Glitch began as an idea in an era of instability and fragility. In this chaos, the path of failure sometimes appears as the only visible one.
As Samuel Beckett said, “Ever tried. Ever failed. No matter. Try again. Fail again. Fail better.”
The exhibition is inspired by what it means to be an error and by what it means to embrace an error. With the curiosity about how this can be liberating and how it can inform and create new artistic practices, we join forces with the glitch.cool collective to produce an exhibition that explores the glitch aesthetic through music, visual, interactive and generative new media art.

Orbiting the Glitch aims to showcase the work of the collective and how they have evolved over time. The collective is built on and expanded by community-shared knowledge and skills. The glitch.cool discord server has become a hub of audio-visual creatives and for that reason the exhibition aims to acknowledge those members by inviting them to participate with their work.

Taking a step further; after publishing an open call and inviting artists, we discovered collaboration around the word which expands our community and introduces creatives who embrace the error in different ways.

The exhibition consists of the work of forty two artists who orbit the glitch through a variety of mediums and reasons. All of them contribute to the discussion of how technology and art intersect. Where can we find the errors in that intersection and how can we use them to either understand burgeoning fields of technology or simply enjoy the creative process and result?

Consider what failure means and what people believe it means. There are disruptions to what we think of as normal. These disruptions lead to various places. They leave room for reconsidering and critically engaging with channels of communication, interaction, and perception. Sound disruption, lost signals, half finished sentences, looking for the line to come back. All of these glitches have the potential to cause anger and discomfort. But what if we accept them? Isn’t this accepting a new reality where everything is broken?

We accept these errors. These errors have the power to create new possibilities.

Much of the spirit of this exhibition is based on Legacy Russell’s Glitch Feminism: A Manifesto.

This pavilion is one of many in this year's The Wrong Biennale. As the curator, I invite you to check the link https://thewrong.org/ to explore the many other pavilions online as well as embassies, which include live exhibition spaces. I am very grateful to the biennale organizers as well as to the New Art City organizers for providing this opportunity for myself and the other artists to share our work. The works here may be experienced as if one is a phantom viewing the objects from the outside as well as passing through their walls to interior spaces, which include video, image, and sound, surrounding and enveloping the viewer who crosses over to the mysterious inside of the cubes and spheres.

Anne Murray is an artist, writer, and also the curator of this exhibition. Her work explores human and other, language and absence, identifying new pathways to connect, while imagining herself as both an octopus and a stone. This research manifests in various media including poetry, video, installation, performance, photography, social practice, and art criticism. Educated with a BFA from Parsons School of Design in Paris, MFA and MS in Art History from Pratt Institute in New York, and M.Ed. from The College of New Jersey Global Studies Program, Mallorca, she now lives in Budapest. Her video work Exquisite Exodus was included in Cf as part of the Research Pavilion curated by Jeanette Doyle at the Venice Biennale in and at La Biennale Méditerranéenne d’Art Contemporain d’Oran, Algeria. She has exhibited in Europe, Asia, and the United States.
www.annemurrayartist.com

Holly Crawford has used text performance, painting, drawing, installation, sound, video, sculpture to grapple with gender, race, and societal concerns for four decades. Installations and performances include: If I’m, who are you?...; Critical Conversations in a Limo (and books); May I have your autograph?; Open Adoption for Art; 13 Ways of Looking at a Blackbird; Offerings; The Dinner Party; The Road: The Century Freeway; Orphans; Water! Water$ Water?; Voice Over; In the Waiting Room, Your Past, Present and Future; and Art Alchemy and the Gift. Her projects have been seen and heard from California to the Tate, Venice to Berlin and Athens to Australia. Her books include, Attached to the Mouse, and catalogue essay, “Disney and Pop” in Once Upon a Time Walt Disney Studio, Artistic Bedfellows, ed., and 7 Days, My Art Life, ed. She is art historian. Her Ph.D. is from the University of Essex in Art History and Theory, BA (Economics, started in the Art Department), MA (Economics) and MS (Behavioral Science) are from UCLA. She taught in the Art Department at UCLA and at SVA. She founded and Directs AC Institute, in NYC, for experimental art and books. http://art-poetry.info/

Willemijn Bouman: "I am a visual artist and designer born in The Netherlands and paint large and colorful canvasses in an abstract expressionistic style. Also I make woodblock prints and frottage (rubbing) in a specific style and technique.

I design and execute projects of applied art, with a specialism in functional visual art (wall paintings and ceramic walls) in parking buildings.

My painting studio nowadays is in Otterlo, The Netherlands (Veluwe).
Also I worked many years in my cave studio in Cappadocia, Turkey and the influence of the Turkish culture and the bizarre landscape of Cappadocia is visible in my artwork.
My large cave house in Turkey was also an artist run micro–art-residency Babayan Culture House. It offered space for many years to international artists. Specialty was community–based art and the interacting with the cave dwellings and weird volcanic landscape. Experimental creations and performing in situ was encouraged.

Besides painting I experiment with different materials and take videos to document my creative processes. Sometimes I create stop motion films."

Emireth Herrera Valdés was born in Mexico, she is a modern and contemporary art curator based in New York. Her focus on social purposes led her to create the virtual gallery Art Within All to create a safe, creative, and healing space where artists are invited to share their art around relevant social topics. Since , she has curated special exhibitions at various galleries and museums such as the Institute of Fine Arts in NYU, Flux Factory, Queens Museum in New York City. In , she was part of the AROS Museum's public program in Denmark. As an art educator, she has collaborated with MARCO Museum multiple times through the Universidad Autonoma de Coahuila. Her research interests include Latin American modern and contemporary art, photography, time-based media, and performance art.

Alexandra Krolikowska was born in Donetsk.
"I am a multidisciplinary artist, cultural activist and psychologist. Inspired by the
therapeutic power of art, I explore the relations of personal and collective mythology, and the modern role of archetypes and psychological rituals.
Utilizing means of photography, video and performance, and being curious how art continues to bear its transformative function within the digital era, I combine analog technologies with futuristic visions.
Researching the concept of metamodernity, I pay special attention to the dualistic perceptions, unveiling in her works the nature of wholeness, embracing poles and seeing beyond.
Also, since I have been a member of the Krolikowski Art duo, sharing collaborative creative practice with Alexander Krolikowski who has similar interests and conceptual perspectives.

From , I was helping with artistic practice in different ways to several Ukrainian
artists: Tanya Fishmann with defining her personal art style of performances, Elis Luna with her collage project, Alevtina Kakhidze with her research on gender equality in the Ukrainian art scene. As invited curator and mentor I was organizing the discussion program and guiding projects for young artists within Nazar Voytovych Art residence (Travneve village in Ukraine) for several weeks."

Lina Vincent has been an independent arts practitioner since , who has worked on multi-layered projects that highlighted plural approaches, a commitment towards socially conscious practices, with a focus on inclusivity and collaboration in public arts engagement. It has resulted in interconnected bodies of research and curation, that bring together diverse voices, modes of expression, and interfaces for dialogue (physical & virtual). The focus areas of her research extend to projects with arts education, printmaking history and practice, the documentation of living traditions and folk arts in India, and environmental consciousness in the arts. Her current practice foregrounds sustained engagement with material culture and social history, seen through acts of community interaction, documentation and display; archiving and interpretation. She continues to explore her training in the arts through participation in multidisciplinary arts projects and experimenting with drawing and photography.
She is heading the Sunaparanta Arts Initiator Lab, Goa (S.A.I.L) in -22 initiated and ran the Piramal Residency Artist Incubator Programme -20. Lina is Associate Curator with ARTPORT_making waves and runs the Goa Familia archival photography project with Serendipity Arts Foundation. She concluded an Archival Museum Fellowship through India Foundation for the Arts for Goa Chitra Museum (-19). Selected recent curatorial projects include ‘TRANSIT- where do we go from here’, APRE art house, Bikaner House, Delhi ; ‘Licence to Laugh’, Shrishti Gallery, Hyderabad ; ‘GOOD FOOD India’ -international arts program for climate-change awareness (-18); Story of Space – multidisciplinary public arts program, Goa (); ‘Tabiyat: Medicine and Healing in India’ CSMVS Mumbai (-17). She has curated numerous exhibitions with galleries across India and continues to contribute to publications and symposiums on art history and contemporary cultural practices.
Lina has a BFA in printmaking from Bangalore University and MFA in Art History from the same institution.

Myriam Ait El Hara has been a professional artist since ."I evolve every day towards new pictorial experiences to approach all techniques, from drawing and calligraphy to painting, installation and photography, I have exhibited in Algeria and around the world (France, Spain, Germany, Syria, Tunisia, Morocco, etc.) Artistic production residencies have brought me into contact with international artists with whom I have exchanged artistic and cultural experiences. My vision for life has been enriched thanks to multiple exhibitions, residencies, experimental workshops and encounters. Each of my works carries with it a large part of my story. These fragmented, deconstructed and then reconstituted bodies are the sum of all the materials that make us up. I use in my installations the magma of our existence, mixed with clay, water and air, giving my subjects a transcendent momentum. My latest productions are a response to all our fears, apprehensions and fears following narcissistic wounds that alter our body image. It is my way of exorcising slices of life, detaching myself from matter and broadening the spectrum of my knowledge of Man. My studies at the School of Fine Arts allow me to know the artist, his aspirations and his needs. My administrative function at the AARC Agency gives me easy access to this world of the arts that I encounter every day and allows me to discover artists from all walks of life and produce them, this enriches me and broadens my knowledge of arts and artists.

Notes for the future monument, brings together practitioners working on the LCC UAL Photography program.

The exhibition is split into four thematic spaces; the room titles relating to urgencies identified through theoretical and practical concerns of student work. ‘Notes for the future monument’ is accompanied by a substantial theoretical text –a copy of which is available for you to download from this room. Within the pages you can read sixteen long form essays produced during the program which also act to expand upon themes and concerns dealt with through practice.

What is remarkable about these texts and the visual work produced in the exhibition is not solely that it was created in the midst of a global pandemic. It is rather because practitioners in the show not only point towards current states of emergency, but offer new understandings, positions and hope toward urgent global and local issues.

The room entitled, Picturing New Practices, is filled with student voices. In this space you can listen to how work is conceived, produced and conceptualised. Foregrounded in this space is the passion and playfulness with which ideas are engaged with - whatever the specificity of the concern.

Acknowledgements

Curation of the show was facilitated by guest practitioners Tom Milnes, Anna Nazo, Krasimira Butseva and Max Colson. We also had a dedicated team of co-curators - Bart Seng Wen Long, Maria Blaga, Anna Janberga, Alexandra Wansell, Lai Lam Fave, Juliusz Grabianski, Anna Komitska, Ruiqi Li, Danielle Anderson and Shane Sutherland – who have been working tirelessly to bring the show to life.

The publication Notes for the future monument was facilitated by Paul Tebb, designed by Jake Richardson and written by members of the BAP3 Cohort.

A special thank-you is reserved for the Third Year Tutors – Beverley Carruthers, Sheyi Bankale, Paul Tebbs, Tom Hunter, Lee Mackinnon, Krasimira Butseva, Atsuhide Ito, Ileana-Lucia Selejan, Derek Wiafe, Tom Seymour, Sophy Rickett, Lalu Delbracio, Yuxin Jiang, Felicity Hammond, Max Colson, Adrian Wood as well as the visiting speakers who have contributed to the program this year

To the technicians -Wendy Ennis, Daniel Salmon, Mary Jennings, Cora James, Burkhard Vogeler, Adrian Wood
D Wiafe, Niamh Sutton, Adam Razvi, Anya Gorkova, Phoebe Somerfield - who are the backbone of the program, and without whose commitment to the student's work would not be made - we salute you.

For further info about the course
https://www.arts.ac.uk/subjects/photography/undergraduate/ba-hons-photography-lcc

Please also visit the UAL Showcase – to see all the other work being produced at UAL
https://www.arts.ac.uk/students/ual-graduate-showcase

Peter Ainsworth
CL Photography LCC UAL

«i Kiss: Greet Your Great Friends» is based on Jacques Derrida’s subversive thoughts, exploring the ways to deconstruct the unilateral relationship of human beings with animals and make a new connection.
Factory farming system that emerged after the Industrial Revolution, that is, artificial reproduction and slaughter, reckless hunting and the destruction of ecosystems due to forest development, now clearly turn up ominous symptom. Natural disasters, the disappearance of seasons, and the climate crisis have evoked many discourses surrounding life and animals, and repeated creation and conflicts. Environment groups have emerged, and the controversial concept - animal rights emerged. However, in today's society, which is deeply intertwined with capital and science, such movement is too weak, so development and destruction are accelerating towards socio Entropy.
What attempts can we make to disassemble deeply intertwined and firmly entrenched mechanical capitalism in society? We can find something for this in the text «L'animal que donc je suis (à suivre)» published by Derrida.
Derrida rethinks the whole meaning of suffer for animal others through philosophical deconstruction, and suggests reviewing the whole recognition system through problems of suffering common to humans and animals instead of language, the framework of human intellect. He evoked the absolute passivity of suffering, and summoned the fundamental feelings of compassion not only for animals but also for life as a whole, including humans. And what we're given in the end would be a question of the relationship between animals and humans.
This exhibition re-translates the paradigm of animals, which has been defined in human language, adopting by Derrida's suggestion. Starting in this point, we might be able to find a clue to genuine coexistence, not only for human beings. We review the relationships within the neoliberal worldview where humans and animals are mixed, examine how they existed, destroy the paradigm, and reconnect animals and me through visual experience.
First, in section , we re-construct animals presence and their connection with surroundings in their natural states. Focusing on animals as creatures living finite lives, we examine the interrelationships of the numerous societies and actors surrounding them.
Next, section deconstruct the fauna connected with people as the object of affection. With the recent sharp expand in the pet industry, high knowledge and obligations of animals as caregivers or protectors tend to be required. On the other hand, we look at the newly emerging animal fauna called “Companion animals”.
In the last section , we will examine the images of symbolic animals that have become separate from their natural context and take new characters. Animals have been positioned as divine beings, or abstract symbols since humankind society was built. The deified animal has been separated from its intrinsic position, get immortal life, and has been misunderstood or worshiped. We will figure out how these aspects of animals relate to human culture and also how these things are affecting real animals.
«i Kiss: Greet Your Great Friends» imagines these heterogeneous networks of animals-human beings with eight artists who show outstanding insight about animals and explores the possibility of new - sustainable - relationships and coexistence of the world that will arrive. Through various media and themes such as painting, digital painting, video, sound, and branding design, we deconstruct the connection between humans and animals and expect to shift the perception structure.

Want more information on Zhaoyue Screens? Feel free to contact us.

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Clelland, Claire Dudley; Fan, Li; Saloner, Rowan; Etchegaray, Jon Iker; Altobelli, Chad Richard; Salomonsson, Sally; Maltos, Alisha M.; Sachdev, Aradhana; Zhu, Jingjie; Lee, Se-In; Li, Yaqiao; Zhou, Yungui; Le, David; Wang, Chao; Carling, Gillian; Kodama, Lay; Sayed, Faten; Perez-Bermejo, Jaun A.; Geier, Ethan G.; Yokoyama, Jennifer S.; Rosen, Howie; Nana, Alissa L.; Spina, Salvatore; Grinberg, Lea T.; Seeley, William W.; Elahi, Fanny; Boxer, Adam L.; Arkin, Michelle R.; Gan, Li SomaScan Hou, X. et al. Machine-learning based strategy identifies a robust protein biomarker panel for Alzheimer’s disease in cerebrospinal fluid Alzheimers Res Ther. Hou, Xiaosen; Qiu, Yunjie; Li, Hui; Yan, Yan; Zhao, Dongxu; Ji, Simei; Ni, Junjun; Zhang, Jun; Liu, Kefu; Qing, Hong; Quan, Zhenzhen SomaScan Rohden, F. et al. Glial reactivity correlates with synaptic dysfunction across aging and Alzheimer’s disease Nat Commun. Rohden, Francieli; Ferreira, Pamela C. L.; Bellaver, Bruna; Ferrari-Souza, João Pedro; Aguzzoli, Cristiano S.; Soares, Carolina; Abbas, Sarah; Zalzale, Hussein; Povala, Guilherme; Lussier, Firoza Z.; Leffa, Douglas T.; Bauer-Negrini, Guilherme; Rahmouni, Nesrine; Tissot, Cécile; Therriault, Joseph; Servaes, Stijn; Stevenson, Jenna; Benedet, Andrea L.; Ashton, Nicholas J.; Karikari, Thomas K.; Tudorascu, Dana L.; Zetterberg, Henrik; Blennow, Kaj; Zimmer, Eduardo R.; Souza, Diogo; Rosa-Neto, Pedro; Pascoal, Tharick A. SomaScan Lopez-Silva, C. et al. Circulating Proteins for Prediction of Kidney Disease Progression and Cardiovascular Outcomes: Individual Participant Data Meta-Analysis of Four Cohorts Am J Nephrol. Lopez-Silva, Carolina; Surapaneni, Aditya; Coresh, Josef; Chen, Teresa K; Schlosser, Pascal; Rhee, Eugene P; Waikar, Sushrut S; Schmidt, Insa M; Deo, Rajat; Ganz, Peter; Dubin, Ruth; Ramachandran, Vasan S; Kimmel, Paul L; Schrauben, Sarah; Parikh, Chirag R; Bonventre, Joseph V; Dobre, Mirela; Rao, Panduranga S; Ricardo, Ana C; Weir, Matthew R; Grams, Morgan E; Investigators, CRIC Study SomaScan Krause, A. et al. Heterozygous MYH7 R403Q mutation impairs left atrial mitochondrial function in a Yucatan mini-pig model of genetic non-obstructive hypertrophic cardiomyopathy J Appl Physiol. Krause, Alexa; Kelty, Taylor J.; Meers, Grace M.; Russell, Alan J.; Evanchik, Marc J; Barthel, Ben; Emter, Craig A.; Rector, R. Scott SomaScan Steitz, A. et al. Elucidating the mechanistic role of ovarian cancer biomarkers: Lessons learnt from affinity-proteomics Crit Rev Oncol Hematol. Steitz, Anna Mary; Reinartz, Silke; Beutgen, Vanessa M.; Müller, Rolf; von Strandmann, Elke Pogge; Gómez-Serrano, María SomaScan Guzman, DE. et al. Proteomic discovery analysis of quantitatively assessed emphysema in the general population. The MESA Lung Study Respir Res. Guzman, Daniel E.; Ruvuna, Lisa; Guo, Claire J.; Sun, Yifei; Pratte, Katherine A.; Manichaikul, Ani W.; Kim, John S.; Post, Wendy S.; Bertoni, Alain G.; Allen, Norrina B.; Watson, Karol E.; Pankow, James S.; Hoffman, Eric A.; Dubin, Ruth F.; Deo, Rajat; Barjaktarevic, Igor Z.; Bleecker, Eugene R.; Cooper, Christopher B.; Ortega, Victor E.; Hastie, Annette T.; Paine, Robert; Wells, James Michael; Curtis, Jeffrey L.; Silverman, Edwin K.; Woodruff, Prescott G.; Garcia, Christine Kim; Rotter, Jerome I.; Bowler, Russell P.; Ganz, Peter; Barr, R. Graham SomaScan Candia, J. et al. SomaScan Bioinformatics: Normalization, Quality Control, and Assessment of Pre-Analytical Variation Methods Mol Biol. Candia, Julián SomaScan Zhao, X. et al. Proteome-wide Mendelian randomization and colocalization analysis identify therapeutic targets for stroke BMC Neurol. Zhao, Xueling; He, Menghao; Zhou, Desheng; Li, Zhong; Liu, Lijuan; Yang, Renyi; Zhu, Xinhua; Gong, Cuilan; Yan, Siyang SomaScan Chekka, L. et al. Characterization of Proteomic Pharmacodynamic Biomarkers of IFNβ-1a Biologics to Inform Potential Utility in Biosimilar Development Clin Pharmacol Ther Chekka, Lakshmi Manasa S.; Samarth, Deepti P.; Guo, Yan; Mohamed, Esraa G.; Decker, Erica; Matta, Murali K.; Sun, Qin; Wheeler, William; Sanabria, Carlos; Wommack, Joel; Gogain, Joseph; Schrieber, Sarah J.; Florian, Jeffry; Wang, Yow‐Ming; Strauss, David G.; Hyland, Paula L. SomaScan Zamani, P. et al. Aortic valve-specific genes dysregulated in calcific aortic valve stenosis as potential biomarkers and therapeutic targets HGG Adv. Zamani, Pardis; Houessou, Ursula; Manikpurage, Hasanga D.; Li, Zhonglin; Dahmene, Manel; Gaudreault, Nathalie; Dagenais, François; Clavel, Marie-Annick; Pibarot, Philippe; Arsenault, Benoit J.; Mathieu, Patrick; Bossé, Yohan; Thériault, Sébastien SomaScan Shvetcov, A. et al. Proteome profiling of cerebrospinal fluid using machine learning shows a unique protein signature associated with APOE4 genotype Aging Cell Shvetcov, Artur; Thomson, Shannon; Cho, Ann‐Na; Wilkins, Heather M.; Reed, Joanne H.; Swerdlow, Russell H.; Brown, David A.; Initiative, the Alzheimer's Disease Neuroimaging; Finney, Caitlin A. SomaScan Zhu, F. et al. Dynamic causal effects of gut microbiota on cervical Cancer lesion progression Sci Rep. Zhu, Fei; Li, Li; Zhang, Huiqi; Liu, Jing; Wu, Dongmei; Xu, Qin SomaScan Boucly, A. et al. Clustering Pulmonary Hypertension Patients Using the Plasma Proteome Am J Respir Crit Care Med. Boucly, Athénaïs; Song, Shanshan; Keles, Merve; Wang, Dennis; Howard, Luke S; Humbert, Marc; Sitbon, Olivier; Lawrie, Allan; Thompson, A A Roger; Frank, Philipp; Kivimaki, Mika; Rhodes, Christopher J; Wilkins, Martin R SomaScan Andresen, I. et al. Maternal Plasma Proteins Associated with Birth Weight: A Longitudinal, Large Scale Proteomic Study J Proteome Res Andresen, Ina Jungersen; Westerberg, Ane Cecilie; Roland, Marie Cecilie Paasche; Zucknick, Manuela; Michelsen, Trond Melbye SomaScan Solomon, M. et al. The Impact Of Modern Industrialized Dietary Sodium Intake On The Plasma Proteome Am J Hypertens Solomon, Melinda; Heydarpour, Mahyar; Tsai, Laura C; Honzel, Brooke; Brown, Jenifer; Newman, Andrew J; Parisien-LaSalle, Stefanie; Wang, Thomas J; Wei, Jin; Zhang, Jie; Waikar, Sushrut; Vaidya, Anand SomaScan Wang, Q. et al. Identification of novel biomarkers and drug targets for frailty-related skeletal muscle aging: a multi-omics study QJM Wang, Qijun; Zhao, Xuan; Wang, Wei; Chen, Xiaolong; Lu, Shibao SomaScan Niu, J. et al. Dissecting immune-mediated pathways in rheumatoid arthritis: A multivariate mediation analysis of antibodies and circulating proteins Sci Rep. Niu, Jingmin; Zhang, Pingxin; Liu, Wei; Sun, Song; Zhang, Yingkai; Sang, Jinghao; Yang, Jialin; Zhang, Qin; Chai, Limin SomaScan Munsch, G. et al. A Multi-Omics Approach Reveals Novel Regulators of Plasma Factor V Levels: highlight on CLEC4M as a Clearance Receptor Blood Munsch, Gaëlle; Mohapatra, Adarsh K; Vlieg, Astrid van Hylckama; Kleber, Marcus E.; Martinez-Perez, Angel; Le, Ngoc-Quynh; Hindberg, Kristian Dalsbø; Dusart, Philip; Germain, Marine; Thibord, Florian; Deleuze, Jean-François; Delgado, Graciela E.; Goumidi, Louisa; Suchon, Pierre; Saut, Noémie; Souto, Juan-Carlos; Butler, Lynn M; Soria, Jose-Manuel; Hansen, John-Bjarne; März, Winfried; Rosendaal, Frits R.; Castoldi, Elisabetta; Peiretti, Franck; Sabater-Lleal, Maria; Trégouët, David-Alexandre; Morange, Pierre-Emmanuel SomaScan Koprulu, M. et al. Sex differences in the genetic regulation of the human plasma proteome Nat Commun. Koprulu, Mine; Wheeler, Eleanor; Kerrison, Nicola D.; Denaxas, Spiros; Carrasco-Zanini, Julia; Orkin, Chloe M.; Hemingway, Harry; Wareham, Nicholas J.; Pietzner, Maik; Langenberg, Claudia SomaScan Damoah, C. et al. Elevated Plasma MBL Levels Are Associated With Risk of Future Venous Thromboembolism: HUNT Arterioscler Thromb Vasc Biol. Damoah, Christabel Esi; Valderhaug, Solveig M; Snir, Omri; Hindberg, Kristian Dalsbø; Brækkan, Sigrid K; Grover, Steven P; Nøst, Therese H; Gál, Péter; Pál, Gábor; Jonasson, Christian; Garred, Peter; Mollnes, Tom Eirik; Hveem, Kristian; Hansen, John-Bjarne SomaScan Chen, Y. et al. Cerebrospinal Fluid CCL25 as a Biomarker for Alzheimer's Disease: Associations with Pathology, Neurodegeneration, and Cognitive Decline Mol Neurobiol. Chen, Yu-Han; Wang, Zhi-Bo; Liu, Xi-Peng; Mao, Zhi-Qi SomaScan Lu, J. et al. Genetic insights support PARP1 as a mediator in the protective association of ATP-citrate lyase inhibitors with melanoma Commun Biol. Lu, Jiawen; Li, Gloria Hoi-Yee; Hu, Jingyi; Wang, Zhenqian SomaScan Wang, . et al. Integrating single-cell with transcriptome-proteome Mendelian randomization reveals colorectal cancer targets Discov Onc. Wang, Song; Yao, Xin; Li, Shenshen; Wang, Shanshan; Huang, Xuyu; Zhou, Jing; Li, Xiao; Wen, Jieying; Lan, Weixuan; Huang, Yunsi; Li, Hao; Sun, Yunlong; Zhao, Xiaoqian; Chen, Qiaoling; Han, Xuedong; Zhu, Ziming; Zhang, Xinyue; Zhang, Tao SomaScan Zhang, M. et al. Decoding the mystery between hyperuricemia and atrial fibrillation: new causal links through mediating proteomics Front. Endocrinol. Zhang, Meiwei; Shi, Lei; Qin, Cong; Peng, Mengling; Zhang, Zhiguo SomaScan Altieri, A. et al. LL-37 and citrullinated-LL-37 modulate IL-17A/F-mediated responses and selectively suppress Lipocalin-2 in bronchial epithelial cells J Inflamm (Lond). Altieri, Anthony; Lloyd, Dylan; Ramotar, Padmanie; Does, Anne M van der; Hemshekhar, Mahadevappa; Mookherjee, Neeloffer SomaScan Liu, H. et al. Ubiquitin–proteasome system in the different stages of dominantly inherited Alzheimer’s disease Alzheimers Dement Liu, Haiyan; Bui, Quoc; Hassenstab, Jason; Gordon, Brian A.; Benzinger, Tammie L. S.; Timsina, Jigyasha; Sung, Yun Ju; Karch, Celeste; Renton, Alan E.; Daniels, Alisha; Morris, John C.; Xiong, Chengjie; Ibanez, Laura; Perrin, Richard J.; Llibre‐Guerra, Jorge J.; Day, Gregory S.; Supnet‐Bell, Charlene; Xu, Xiong; Berman, Sarah B.; Chhatwal, Jasmeer P.; Ikeuchi, Takeshi; Kasuga, Kensaku; Niimi, Yoshiki; Huey, Edward D.; Schofield, Peter R.; Brooks, William S.; Ryan, Natalie S.; Jucker, Mathias; Laske, Christoph; Levin, Johannes; Vöglein, Jonathan; Roh, Jee Hoon; Lopera, Francisco; Bateman, Randall J.; Cruchaga, Carlos; McDade, Eric M.; team, For DIAN study SomaScan Ye, H. et al. NMRAL1 as a Causal Factor in Postherpetic Neuralgia: A Proteome-Wide Mendelian Randomization Study Cell Death Dis Ye, Hong; Wang, Yiling; Shi, Yuechun; Wu, Yuyu; Xu, Qiuhan; Huang, Songmin SomaScan El‐Sabawi, B. et al. Circulating Proteomics Identifies a Dynamic Profile of Hepatic Steatosis During Metabolic Intervention J Am Heart Assoc. El‐Sabawi, Bassim; Tanriverdi, Kahraman; Gajjar, Priya; Nayor, Matthew; Landman, Joshua M; Below, Jennifer E; Haff, Madeleine; Long, Michelle; Ezpeleta, Mark; Freedman, Jane E; Varady, Krista; Shah, Ravi; Perry, Andrew S SomaScan Harel, M. et al. Decoding resistance to immune checkpoint inhibitors in non-small cell lung cancer: a comprehensive analysis of plasma proteomics and therapeutic implications J Immunother Cancer Harel, Michal; Dahan, Nili; Lahav, Coren; Jacob, Eyal; Elon, Yehonatan; Puzanov, Igor; Kelly, Ronan J; Shaked, Yuval; Leibowitz, Raya; Carbone, David P; Gandara, David R; Dicker, Adam P SomaScan Dong, Z. et al. Roles of plasma proteins in mediating the causal effect of the lipid species on gastric cancer: Insights from proteomic and two-step Mendelian randomization Medicine (Baltimore). Dong, Zhenhua; Chen, Zhiqing; Yu, Kai; Zhao, Dingliang; Jia, Jianling; Gao, Xulei; Wang, Daguang SomaScan Li, O. et al. Relationships between neuropsychiatric symptoms, subtypes of astrocyte activities, and brain pathologies in Alzheimer's disease and Parkinson's disease Alzheimers Dement. Li, Oceanna Yueran; Shin, Steven; Zhou, Sa; Turnbull, Adam; Lin, F. Vankee; Initiative, for the Alzheimer's Disease Neuroimaging SomaScan Oliva, V. et al. Predicted plasma proteomics from genetic scores and treatment outcomes in major depression: a meta-analysis Eur Neuropsychopharmacol. Oliva, Vincenzo; Possidente, Chiara; Fanelli, Giuseppe; Domschke, Katharina; Minelli, Alessandra; Gennarelli, Massimo; Martini, Paolo; Bortolomasi, Marco; Squassina, Alessio; Pisanu, Claudia; Kasper, Siegfried; Zohar, Joseph; Souery, Daniel; Montgomery, Stuart; Albani, Diego; Forloni, Gianluigi; Ferentinos, Panagiotis; Rujescu, Dan; Mendlewicz, Julien; Baune, Bernhard T; Network, European College of Neuropsychopharmacology (ECNP) Pharmacogenomics Transcriptomics; Vieta, Eduard; Serretti, Alessandro; Fabbri, Chiara SomaScan Heo, G. et al. Large-scale plasma proteomic profiling unveils diagnostic biomarkers and pathways for Alzheimer’s disease Nat Aging  Heo, Gyujin; Xu, Ying; Wang, Erming; Ali, Muhammad; Oh, Hamilton Se-Hwee; Moran-Losada, Patricia; Anastasi, Federica; Escalante, Armand González; Puerta, Raquel; Song, Soomin; Timsina, Jigyasha; Liu, Menghan; Western, Daniel; Gong, Katherine; Chen, Yike; Kohlfeld, Pat; Flynn, Allison; Thomas, Alvin G.; Lowery, Joseph; Morris, John C.; Holtzman, David M.; Perlmutter, Joel S.; Schindler, Suzanne E.; Vilor-Tejedor, Natalia; Suárez-Calvet, Marc; García-González, Pablo; Marquié, Marta; Fernández, Maria Victoria; Boada, Mercè; Cano, Amanda; Ruiz, Agustín; Zhang, Bin; Bennett, David A.; Benzinger, Tammie; Wyss-Coray, Tony; Ibanez, Laura; Sung, Yun Ju; Cruchaga, Carlos SomaScan Duggan, M. et al. Proteomic signatures of corona and herpes viral antibodies identify IGDCC4 as a mediator of neurodegeneration Sci Adv. Duggan, Michael R.; Yang, Shuojia; Gomez, Gabriela T.; Cui, Yuhan; Capuano, Ana W.; Chen, Jingsha; Yang, Zhijian; Wen, Junhao; Erus, Guray; Drouin, Shannon M.; Zweibaum, David; Tian, Qu; Candia, Julián; Bilgel, Murat; Lewis, Alexandria; Moghekar, Abhay; Ashton, Nicholas J.; Kac, Przemysław R.; Karikari, Thomas K.; Blennow, Kaj; Zetterberg, Henrik; Maher, Brion S.; Spira, Adam P.; Dumitrescu, Logan; Hohman, Timothy J.; Gottesman, Rebecca F.; Davatzikos, Christos; Bennett, David A.; Coresh, Josef; Ferrucci, Luigi; Resnick, Susan M.; Yolken, Robert; Walker, Keenan A. SomaScan Li, X. et al. Therapeutic targets for venous thromboemblism: proteome-wide mendelian randomization and colocalization analyses Thrombosis J. Li, Xiaolong; Yang, Cheng-hao; Zhou, Min; Yin, Min-yi SomaScan Courtney, Y. et al. Choroid plexus apocrine secretion shapes CSF proteome during mouse brain development Nat Neurosci Courtney, Ya’el; Head, Joshua P.; Dani, Neil; Chechneva, Olga V.; Shipley, Frederick B.; Zhang, Yong; Holtzman, Michael J.; Sadegh, Cameron; Libermann, Towia A.; Lehtinen, Maria K. SomaScan Oh, H. et al. A cerebrospinal fluid synaptic protein biomarker for prediction of cognitive resilience versus decline in Alzheimer’s disease Nature Med. Oh, Hamilton Se-Hwee; Urey, Deniz Yagmur; Karlsson, Linda; Zhu, Zeyu; Shen, Yuanyuan; Farinas, Amelia; Timsina, Jigyasha; Duggan, Michael R.; Chen, Jingsha; Guldner, Ian H.; Morshed, Nader; Yang, Chengran; Western, Daniel; Ali, Muhammad; Le Guen, Yann; Trelle, Alexandra; Herukka, Sanna-Kaisa; Rauramaa, Tuomas; Hiltunen, Mikko; Lipponen, Anssi; Luikku, Antti J.; Poston, Kathleen L.; Mormino, Elizabeth; Wagner, Anthony D.; Wilson, Edward N.; Channappa, Divya; Leinonen, Ville; Stevens, Beth; Ehrenberg, Alexander J.; Gottesman, Rebecca F.; Coresh, Josef; Walker, Keenan A.; Zetterberg, Henrik; Bennett, David A.; Franzmeier, Nicolai; Hansson, Oskar; Cruchaga, Carlos; Wyss-Coray, Tony SomaScan Zhu, Q. et al. Appraising the causal role of cathepsins in genitourinary carcinoma: a two-sample mendelian randomization and prospective study based on 36,225 individuals Discov Onc Zhu, Qiyu; Liu, Dingbang; Liu, Haoyang; Pan, Xiaohui; Shi, Yifu; Guo, Jingjing; Tong, Nanwei; Chen, Junru; Zeng, Hao SomaScan Eltobgy, M. et al. Plasma proteomic profiles correlate with organ dysfunction in COVID-19 ARDS Physiol Rep. Eltobgy, Moemen; Klamer, Brett; Farkas, Daniela; Londino, James D.; Englert, Joshua A.; Horowitz, Jeffrey C.; Mallampalli, Rama K.; Brock, Guy; Bednash, Joseph S. SomaScan Kitani, A. et al. Integrative network analysis reveals novel moderators of Aβ-Tau interaction in Alzheimer's disease Alzheimers Res Ther. Kitani, Akihiro; Matsui, Yusuke SomaScan Oliva, M. et al. Integration of GWAS, QTLs and keratinocyte functional assays reveals molecular mechanisms of atopic dermatitis Nat Commun. Oliva, Meritxell; Sarkar, Mrinal K.; March, Michael E.; Saeidian, Amir Hossein; Mentch, Frank D.; Hsieh, Chen-Lin; Tang, Fanying; Uppala, Ranjitha; Patrick, Matthew T.; Li, Qinmengge; Bogle, Rachael; Kahlenberg, J. Michelle; Watson, Deborah; Glessner, Joseph T.; Youssefian, Leila; Vahidnezhad, Hassan; Tsoi, Lam C.; Hakonarson, Hakon; Gudjonsson, Johann E.; Smith, Kathleen M.; Riley-Gillis, Bridget SomaScan Kuku, K. et al. Proteomic Profile of Ischemic Heart Disease in Heart Failure: A Community Study Mayo Clin Proc. Kuku, Kayode O.; Hashemian, Maryam; Joo, Jungnam; Shearer, Joseph J.; Downie, Carolina G.; Aggarwal, Mohit; Bielinski, Suzette J.; Roger, Véronique L. SomaScan Wang, L. et al. Associations among Angiotensin-Converting Enzyme, Neuroinflammation, and Cerebrospinal Fluid Biomarkers of Alzheimer's Disease in Non-Dementia Adults Neurotox Res. Wang, Lan-Yang; Hu, Hao; Sheng, Ze-Hu; Hu, He-Ying; Ou, Ya-Nan; Guo, Fan; Zhu, Yang-Ke; Tan, Lan; Initiative, Alzheimer’s Disease Neuroimaging SomaScan Rooney, M. et al.f Correlations Within and Between Highly Multiplexed Proteomic Assays of Human Plasma Clin Chem. Rooney, Mary R; Chen, Jingsha; Ballantyne, Christie M; Hoogeveen, Ron C; Boerwinkle, Eric; Yu, Bing; Walker, Keenan A; Schlosser, Pascal; Selvin, Elizabeth; Chatterjee, Nilanjan; Couper, David; Grams, Morgan E; Coresh, Josef SomaScan Zhao, H. et al. High Throughput Proteomics Using the SomaLogic Platform Methods Mol Biol. Zhao, Hanjun; Winchester, Laura SomaScan Milani, L. et al. The Estonian Biobank’s journey from biobanking to personalized medicine Nat Commun. Milani, Lili; Alver, Maris; Laur, Sven; Reisberg, Sulev; Haller, Toomas; Aasmets, Oliver; Abner, Erik; Alavere, Helene; Allik, Annely; Annilo, Tarmo; Fischer, Krista; Hofmeister, Robin; Hudjashov, Georgi; Jõeloo, Maarja; Kals, Mart; Karo-Astover, Liis; Kasela, Silva; Kolde, Anastassia; Krebs, Kristi; Krigul, Kertu Liis; Kronberg, Jaanika; Kruusmaa, Karoliina; Kukuškina, Viktorija; Kõiv, Kadri; Lehto, Kelli; Leitsalu, Liis; Lind, Sirje; Luitva, Laura Birgit; Läll, Kristi; Lüll, Kreete; Metsalu, Kristjan; Metspalu, Mait; Mõttus, René; Nelis, Mari; Nikopensius, Tiit; Nurm, Miriam; Nõukas, Margit; Oja, Marek; Org, Elin; Palover, Marili; Palta, Priit; Pankratov, Vasili; Pantiukh, Kateryna; Pervjakova, Natalia; Pujol-Gualdo, Natàlia; Reigo, Anu; Reimann, Ene; Smit, Steven; Rogozina, Diana; Särg, Dage; Taba, Nele; Talvik, Harry-Anton; Teder-Laving, Maris; Tõnisson, Neeme; Vaht, Mariliis; Vainik, Uku; Võsa, Urmo; Yelmen, Burak; Esko, Tõnu; Kolde, Raivo; Mägi, Reedik; Vilo, Jaak; Laisk, Triin; Metspalu, Andres SomaScan Sun, X. et al. Uncovering leading compounds for alzheimer’s disease treatment: mendelian randomization and virtual screening insights into plasma protein modulation Biol Res. Sun, Xiaohan; Hu, Xiaofei; Wei, Jianming; An, Haoyu SomaScan Zhou, Y. et al. Genetically druggable targets for MAPK-activated colorectal cancer by a two-sample mendelian randomization analysis Sci Rep. Zhou, Yuxuan; Ding, Yunlong; Xu, Bangyue; Fei, Hongyang; Wang, Zheng SomaScan Zhang, M. et al. Immune status assessment based on plasma proteomics with meta graph convolutional networks BMC Genomics Zhang, Min; Xu, Nan; Cheng, Qi; Ye, Jing; Wu, Shiwei; Liu, Haoliang; Zhao, Chengkui; Yu, Lei; Feng, Weixing SomaScan Xiong, Y. et al. Efficient and scalable construction of clinical variable networks for complex diseases with RAMEN Cell Rep Methods Xiong, Yiwei; Wang, Jingtao; Shang, Xiaoxiao; Chen, Tingting; Fraser, Douglas D.; Fonseca, Gregory J.; Rousseau, Simon; Ding, Jun SomaScan Zhang, X. et al. FNDC4 Prevents Aging-Related Cardiac Dysfunction: By Restoring AMPKα/PPARα-Dependent Mitochondrial Function JACC: BasicTrans. Sci. Zhang, Xin; Dong, Wen-Sheng; Li, Kang; Ye, Yun-Jia; Hu, Can SomaScan Sasamoto, N. et al. Prospective evaluation of plasma proteins in relation to surgical endometriosis diagnosis in the Nurses’ Health Study II EBioMedicine. Sasamoto, Naoko; Ngo, Long H.; Vitonis, Allison F.; Dillon, Simon T.; Aziz, Maryam; Shafrir, Amy L.; Missmer, Stacey A.; Libermann, Towia A.; Terry, Kathryn L. SomaScan Daghlas, I. et al. Association of MTHFR missense variants with thromboembolic diseases and coagulation factor levels in European populations Thromb J. Daghlas, Iyas; Wang, Mengmeng; Gill, Dipender SomaScan Durán-Rodriguez, A. et al. Macrophage Migration Inhibitory Factor Contributes to Adverse Outcomes of Experimental Gestational Malaria across Pregnancy Stages Am J Pathol. Durán-Rodriguez, Andrea Tatiana; Almeida, Marcos Paulo Oliveira; Ferreira, Flávia Batista; Lozano-Trujillo, Laura Alejandra; Gomes, Angelica Oliveira; Cariaco, Yusmaris; Silva, Neide Maria SomaScan Candia, J. et al. Effects of In Vitro Hemolysis and Repeated Freeze–Thaw Cycles in Protein Abundance Quantification Using the SomaScan and Olink Assays J Proteome Res. Candia, Julián; Fantoni, Giovanna; Moaddel, Ruin; Delgado-Peraza, Francheska; Shehadeh, Nader; Tanaka, Toshiko; Ferrucci, Luigi SomaScan De Nardo, W. et al. Integrated liver-secreted and plasma proteomics identify a predictive model that stratifies MASH Cell Rep Med. De Nardo, William; Lee, Olivia; Johari, Yazmin; Bayliss, Jacqueline; Pensa, Marcus; Miotto, Paula M.; Keenan, Stacey N.; Ryan, Andrew; Rucinski, Amber; Svinos, Tessa M.; Ooi, Geraldine J.; Brown, Wendy A.; Kemp, William; Roberts, Stuart K.; Parker, Benjamin L.; Montgomery, Magdalene K.; Larance, Mark; Burton, Paul R.; Watt, Matthew J. SomaScan Assi, I. et al. Correlation between Olink and SomaScan proteomics platforms in adults with a Fontan circulation International Journal of Cardiology Congenital Heart Disease Assi, Ismael Z.; Landzberg, Michael J.; Becker, Kristian C.; Renaud, David; Reyes, Fernando Baraona; Leone, David M.; Benson, Mark; Michel, Miriam; Gerszten, Robert E.; Opotowsky, Alexander R. SomaScan Quan, L. et al. Genetic associations of plasma proteins and breast cancer identify potential therapeutic drug candidates Nat. Commun Biol Quan, Liuliu; Luo, Xin; Meng, Chenxu; Liu, Jinsong; Ju, Jie; Yang, Zixuan; Shuai, You; Wei, Tong; Meng, Jiaqi; Yuan, Peng SomaScan Chen, Y. et al. Identification of Novel Protein Biomarkers for Intrahepatic Cholangiocarcinoma by Integrating Human Plasma Proteome with Genome J Gastrointest Cancer. Chen, Yu-Sen; Yang, Wei-Bang; Li, Yi-Hu; Xu, Jin-Yang; Wei, Yu-Xuan; Huang, Si-Min; Jiang, Xiao-Feng; Li, Jian-Hui SomaScan Lumish, H. et al. Comprehensive Plasma Proteomic Profiling Reveals Differentially Regulated Signaling Pathways Underlying Left Ventricular Hypertrophy Between Hypertrophic Cardiomyopathy and Aortic Stenosis J. Cardiovasc. Transl. Res. Lumish, Heidi S.; Sewanan, Lorenzo R.; Liang, Lusha W.; Hasegawa, Kohei; Maurer, Mathew S.; Reilly, Muredach P.; Shimada, Yuichi J. SomaScan Kim, H. et al. Plant-based diets and cardiovascular events: a proteomics approach to examine the underlying pathways J Nutr. Kim, Hyunju; Chen, Jingsha; Prescott, Brenton; Walker, Maura E.; Grams, Morgan E.; Yu, Bing; Vasan, Ramachandran S.; Floyd, James; Sotoodehnia, Nona; Smith, Nicholas L.; Arking, Dan E.; Coresh, Josef; Rebholz, Casey M. SomaScan Li, Y. et al. Epigenomic and proteomic analyses provide insights into early-life immune regulation and asthma development in infants Nat Commun. Li, Yijun; Zhu, Zhaozhong; Camargo, Carlos A.; Espinola, Janice A.; Hasegawa, Kohei; Liang, Liming SomaScan Di Liberto, G. et al. Neuronal pSTAT1 hallmarks synaptic pathology in autoimmune encephalitis against intracellular antigens Acta Neuropathol. Di Liberto, Giovanni; Egervari, Kristof; Vogrig, Alberto; Spatola, Marianna; Piccinno, Margot; Vincenti, Ilena; Wagner, Ingrid; Kreutzfeldt, Mario; Endmayr, Verena; Ostertag, Karoline; Rahimi, Jasmin; Vicino, Alex; Pröbstel, Anne-Katrin; Meyronet, David; Frank, Stephan; Prinz, Marco; Hewer, Ekkehard; Brouland, Jean-Philippe; de Leval, Laurence; Parkkinen, Laura; Draganski, Bogdan; Desestret, Virginie; Dubey, Divyanshu; Pittock, Sean J.; Roemer, Shanu F.; Dickson, Dennis W.; Höftberger, Romana; Irani, Sarosh R.; Honnorat, Jérôme; Du Pasquier, Renaud; Merkler, Doron SomaScan Manoharan, MS. et al. The 15-Year Survival Advantage: Immune Resilience asa Salutogenic Force in Healthy Aging Aging Cell Manoharan, Muthu Saravanan; Lee, Grace C.; Harper, Nathan; Meunier, Justin A.; Restrepo, Marcos I.; Jimenez, Fabio; Karekatt, Sreenath; Branum, Anne P.; Gaitan, Alvaro A.; Andampour, Kian; Smith, Alisha M.; Mader, Michael; Noronha, Michelle; Tripathy, Devjit; Zhang, Nu; Moreira, Alvaro G.; Pandranki, Lavanya; team, South Texas Veterans Health Care System (STVHCS) COVID‐19 Clinical; team, STVHCS COVID‐19 Vaccine; team, STVHCS COVID‐19 Convalescent care; Medicine, STVHCS Center for Personalized; Sanchez‐Reilly, Sandra; Trinh, Hanh D.; Barnett, Clea; Angel, Luis; Segal, Leopoldo N.; Nicholson, Susannah; Clark, Robert A.; He, Weijing; Okulicz, Jason F.; Ahuja, Sunil K. SomaScan Tutino, M. et al. Genetics of circulating proteins in newborn babies at high risk of type 1 diabetes Nat Commun. Tutino, Mauro; Yu, Nancy Yiu-Lin; Hatzikotoulas, Konstantinos; Park, Young-Chan; Kreitmaier, Peter; Katsoula, Georgia; Berner, Reinhard; Casteels, Kristina; Larsson, Helena Elding; Kordonouri, Olga; Ołtarzewski, Mariusz; Szypowska, Agnieszka; Ott, Raffael; Weiss, Andreas; Winkler, Christiane; Zapardiel-Gonzalo, Jose; Petrera, Agnese; Hauck, Stefanie M.; Bonifacio, Ezio; Ziegler, Anette-Gabriele; Zeggini, Eleftheria SomaScan Solomon, M. et al. Cross-sectional associations of proteomic age acceleration with self-reported physical and mental health and depression symptoms among those with and without cancer J Cancer Surviv. Solomon, Matia; Bhatia, R; Wang, S; Blaes, AH; Platz, EA; Guan, W; Jewett, PI; Prizment, A SomaScan Abou Kamara, S. et al. The plasma proteome is linked to echocardiographic parameters and stages of diastolic dysfunction, across the ejection fraction spectrum Int J Cardiol. Abou Kamara, S; van Ommen, AM; Dal Canto, E; Valstar, G; Akkerhuis, KM; Cramer, MJ; Umans, V; Rutten, F; Teske, AJ; Menken, R; Geleijnse, M; Hofstra, L; Verhaar, M; de Boer, RA; Boersma, E; Asselbergs, F; van Dalen, BM; den Ruijter, H; Kardys, I. SomaScan Pan, J. et al. Genetic Evidence of Causal Effect between C1q/TNF-Related Protein-1 and Atherosclerosis: a Bidirectional and Multivariate Mendelian Randomization Study J Atheroscler Thromb. Pan, Juhong; Huang, Jia; Chen, Yueying; Jiang, Nan; Guo, Yuxin; Zhang, Ji; Zhou, Shiyuan; Pu, Huan; Deng, Qing; Hu, Bo; Zhou, Qing SomaScan Li, W. et al. The prospective approach for aptamers applied in the treatment and molecular diagnostics of ischemic stroke Front. Pharmacol. Li, Wenfeng; Wu, Junyi; Hu, Zijian; Zhang, Jixuan; Ye, Guangming; Luo, Fengling; Zeng, Zhikun; Luo, Yi SomaScan Mogavero, M. et al. Sex Differences in Cerebrospinal Fluid Proteomics of Patients with Restless Legs Syndrome Sleep Mogavero, Maria P; Peng, Gang; Marchese, Giovanna; Lanza, Giuseppe; Ferini-Strambi, Luigi; Ferri, Raffaele; Koo, Brian B SomaScan Tasci, E. et al. GLIO-Select: Machine Learning-Based Feature Selection and Weighting of Tissue and Serum Proteomic and Metabolomic Data Uncovers Sex Differences in Glioblastoma Int. J. Mol. Sci. Tasci, Erdal; Chappidi, Shreya; Zhuge, Ying; Zhang, Longze; Zgela, Theresa Cooley; Sproull, Mary; Mackey, Megan; Camphausen, Kevin; Krauze, Andra Valentina SomaScan Bai, Y. et al. Genetic Evidence Supporting a Causal Association Between mTORC1-Dependent Circulating Protein Levels and Diabetic Retinopathy Transl Vis Sci Technol. Bai, Yaqi; Xi, Yujia; Gui, Chenwei; Huang, Guohai; Zhou, Guohong SomaScan Collister, D. et al. The differential effects of sex hormone therapy on kidney function: insights into biological sex differences J Clin Invest. Collister, David; Levin, Adeera SomaScan Hosseini, M. et al. Plasma Osteopontin Levels Are Associated with Risk of Future Incident Venous Thromboembolism – The HUNT Study J Thromb Haemost. Hosseini, Maryam; Hindberg, Kristian D.; Nøst, Therese H.; Jonasson, Christian; Hveem, Kristian; Hansen, John-Bjarne; Snir, Omri SomaScan Tobin, B. et al. Exploring Human Plasma Proteomic Variations in Mucolipidosis Type IV Mol Ther Methods Clin Dev. Tobin, Brendan R.; Misko, Albert; Miller-Browne, Victoria; Sangster, Madison; Grishchuk, Yulia; Wood, Levi B. SomaScan Commissati, S. et al. Prolonged fasting promotes systemic inflammation and platelet activation in humans: A medically supervised, water-only fasting and refeeding study Mol Metab. Commissati, Serena; Cagigas, Maria Lastra; Masedunskas, Andrius; Petrucci, Giovanna; Tosti, Valeria; De Ciutiis, Isabella; Rajakumar, Gayathiri; Kirmess, Kristopher M.; Meyer, Matthew R.; Goldhamer, Alan; Kennedy, Brian K.; Hatem, Duaa; Rocca, Bianca; Fiorito, Giovanni; Fontana, Luigi SomaScan Loesch, D. et al. Identification of plasma proteomic markers underlying polygenic risk of type 2 diabetes and related comorbidities Nat Commun Loesch, Douglas P.; Garg, Manik; Matelska, Dorota; Vitsios, Dimitrios; Jiang, Xiao; Ritchie, Scott C.; Sun, Benjamin B.; Runz, Heiko; Whelan, Christopher D.; Holman, Rury R.; Mentz, Robert J.; Moura, Filipe A.; Wiviott, Stephen D.; Sabatine, Marc S.; Udler, Miriam S.; Gause-Nilsson, Ingrid A.; Petrovski, Slavé; Oscarsson, Jan; Nag, Abhishek; Paul, Dirk S.; Inouye, Michael SomaScan Tokolyi, A. et al. The contribution of genetic determinants of blood gene expression and splicing to molecular phenotypes and health outcomes Nat Genet. Tokolyi, Alex; Persyn, Elodie; Nath, Artika P.; Burnham, Katie L.; Marten, Jonathan; Vanderstichele, Thomas; Tardaguila, Manuel; Stacey, David; Farr, Ben; Iyer, Vivek; Jiang, Xilin; Lambert, Samuel A.; Noell, Guillaume; Quail, Michael A.; Rajan, Diana; Ritchie, Scott C.; Sun, Benjamin B.; Thurston, Scott A. J.; Xu, Yu; Whelan, Christopher D.; Runz, Heiko; Petrovski, Slavé; Gaffney, Daniel J.; Roberts, David J.; Di Angelantonio, Emanuele; Peters, James E.; Soranzo, Nicole; Danesh, John; Butterworth, Adam S.; Inouye, Michael; Davenport, Emma E.; Paul, Dirk S. SomaScan Niinuma, S. et al. A Cross-Sectional Exploratory Study of Rat Sarcoid (Ras) Activation in Women with and Without Polycystic Ovary Syndrome Cells Niinuma, Sara Anjum; Habib, Haniya; Takemoto, Ashleigh Suzu-Nishio; Das, Priya; Sathyapalan, Thozhukat; Atkin, Stephen L; Butler, Alexandra E SomaScan Belbasis, L. et al. Mendelian randomization identifies proteins involved in neurodegenerative diseases Brain Belbasis, Lazaros; Morris, Sam; van Duijn, Cornelia; Bennett, Derrick; Walters, Robin SomaScan De Oliveira, T. et al. Protein epigenetic scores and overall mortality in the longitudinal Swedish Adoption/Twin Study of Aging (SATSA) Clin Epigenetics. De Oliveira, Thaís Lopes; March, Arianna; Mak, Jonathan K. L.; Pedersen, Nancy L.; Hägg, Sara SomaScan Zhao, Y. et al. Identification of Candidate Lung Function-Related Plasma Proteins to Pinpoint Drug Targets for Common Pulmonary Diseases: A Comprehensive Multi-Omics Integration Analysis Curr. Issues Mol. Biol. Zhao, Yansong; Shen, Lujia; Yan, Ran; Liu, Lu; Guo, Ping; Liu, Shuai; Chen, Yingxuan; Yuan, Zhongshang; Gong, Weiming; Ji, Jiadong SomaScan Chadwick, J. et al. Harnessing the Plasma Proteome to Predict Mortality in Heart Failure Subpopulations Circ Heart Fail. Chadwick, Jessica; Hinterberg, Michael A; Asselbergs, Folkert W; Biegel, Hannah; Boersma, Eric; Cappola, Thomas P; Chirinos, Julio A; Coresh, Joseph; Ganz, Peter; Gordon, David A; Kureshi, Natasha; Loupey, Kelsey M; Orlenko, Alena; Ostroff, Rachel; Sampson, Laura; Shrestha, Sama; Sweitzer, Nancy K; Williams, Stephen A; Zhao, Lei; Kardys, Isabella; Lanfear, David E SomaScan Ali, M. et al. Multi-cohort cerebrospinal fluid proteomics identifies robust molecular signatures across the Alzheimer disease continuum Neuron Ali, Muhammad; Timsina, Jigyasha; Western, Daniel; Liu, Menghan; Beric, Aleksandra; Budde, John; Do, Anh; Heo, Gyujin; Wang, Lihua; Gentsch, Jen; Schindler, Suzanne E.; Morris, John C.; Holtzman, David M.; Ruiz, Agustin; Alvarez, Ignacio; Aguilar, Miquel; Pastor, Pau; Rutledge, Jarod; Oh, Hamilton; Wilson, Edward N.; Le Guen, Yann; Khalid, Rana R.; ADRC), Knight Alzheimer Disease Research Center (Knight; (ADNI), Alzheimer Disease Neuroimaging Initiative; (FACE), Fundació ACE Alzheimer Center Barcelona; Barcelona-1; ADRC), Stanford Alzheimer Disease Research Center (Stanford; Robins, Chloe; Pulford, David J.; Tarawneh, Rawan; Ibanez, Laura; Wyss-Coray, Tony; Sung, Yun Ju; Cruchaga, Carlos SomaScan Kivimäki, M. et al. Social disadvantage accelerates aging Nat Med. Kivimäki, Mika; Pentti, Jaana; Frank, Philipp; Liu, Fangyu; Blake, Acer; Nyberg, Solja T.; Vahtera, Jussi; Singh-Manoux, Archana; Wyss-Coray, Tony; Walker, Keenan A.; Partridge, Linda; Lindbohm, Joni V. SomaScan Rothman, A. et al. Positioning Imatinib for Pulmonary Arterial Hypertension: A Dose Finding Phase 2 Study Am J Respir Crit Care Med Rothman, Alexander M K; Villar, Sofia; Middleton, Jennifer; Roussakis, Andreas A; Varian, Frances; Zafar, Hamza; Law, Martin; Apperley, Jane; Bartelink, Imke H; Said, Medhat M; Delgado-SanMartin, Juan A; Kiely, David G; Howard, Luke; Toshner, Mark; Wort, S John; Wilkins, Martin R SomaScan Yuan, S. et al. GWAS identifies genetic loci, lifestyle factors and circulating biomarkers that are risk factors for sarcoidosis Yuan, Shuai; Chen, Jie; Geng, Jiawei; Zhao, Sizheng Steven; Yarmolinsky, James; Arkema, Elizabeth V.; Abramowitz, Sarah; Levin, Michael G.; Tsilidis, Kostas K.; Burgess, Stephen; Damrauer, Scott M.; Larsson, Susanna C. SomaScan Alakwaa, F. et al. Leveraging complementary multi-omics data integration methods for mechanistic insights in kidney diseases JCI Insight Alakwaa, Fadhl; Das, Vivek; Majumdar, Arindam; Nair, Viji; Fermin, Damian; Dey, Asim B.; Slidel, Timothy; Reilly, Dermot F.; Myshkin, Eugene; Duffin, Kevin L.; Chen, Yu; Bitzer, Markus; Pennathur, Subramaniam; Brosius, Frank C.; Kretzler, Matthias; Ju, Wenjun; Karihaloo, Anil; Eddy, Sean SomaScan Lin, Yu-Jing. et al. The associations of cerebrospinal fluid ApoE and C1q with Alzheimer's disease biomarkers J Alzheimers Dis. Lin, Yu-Jing; Liu, Ying; Sheng, Ze-Hu; Fu, Yan; Ma, Ling-Zhi; Zhang, Zi-Hao; Wang, Lan-Yang; Huang, Liang-Yu; Liu, Min; Wang, Zuo-Teng; Tan, Lan; *, Alzheimer's Disease Neuroimaging Initiative SomaScan Zhang, Xuening; Associations of plasma proteins with incident inflammatory bowel disease in a prospective cohort study and genetic analysis Nat Commun. Zhang, Xuening; Zhao, Hao; Wan, Meng; Man, Jinyu; Zhang, Tongchao; Yang, Xiaorong; Lu, Ming SomaScan Sullivan, V. et al. Proteomic Correlates of Vitamin D Supplementation in the Atherosclerosis Risk in Communities (ARIC) Study Proteomics Clin Appl. Sullivan, Valerie, K.; Chen, Jingsha; Bernard, Lauren; Yu, Bing; Michos, Erin D.; Appel, Lawrence J.; Lichtenstein, Alice H.; Rebholz, Casey M. SomaScan He, Y. et al. Comment on Maddaloni et al. Osteoprotegerin, Osteopontin, and Osteocalcin Are Associated With Cardiovascular Events in Type 2 Diabetes: Insights From EXSCEL. Diabetes Care ;48:235–242 Diabetes Care He, Yanlin; Liu, Chan; Wang, Xiaoping SomaScan Maddaloni, E. et al. Response to Comments on Maddaloni et al. Osteoprotegerin, Osteopontin, and Osteocalcin Are Associated With Cardiovascular Events in Type 2 Diabetes: Insights From EXSCEL. Diabetes Care ;48:235–242 Maddaloni, Ernesto; Nguyen, Maggie; Shah, Svati H; Holman, Rury R SomaScan Stemmerik, M. et al. Universal Proteomic Signature After Exercise-Induced Muscle Injury in Muscular Dystrophies Ann Clin Transl Neurol. Stemmerik, Mads G.; Barthel, Benjamin; Andersen, Nanna R.; Skriver, Sofie V.; Russell, Alan J.; Vissing, John SomaScan Wang, Z. et al. Cerebrospinal fluid proteomics identification of biomarkers for amyloid and tau PET stages Cell Rep Med. Wang, Zhibo; Chen, Yuhan; Gong, Katherine; Zhao, Bote; Ning, Yuye; Chen, Meilin; Li, Yan; Ali, Muhammad; Timsina, Jigyasha; Liu, Menghan; Cruchaga, Carlos; Jia, Jianping SomaScan Nouairia, G. et al. Towards precision medicine strategies using plasma proteomic profiling for suspected gallbladder cancer: a pilot study J Thromb Haemost Nouairia, Ghada; Cornillet, Martin; Jansson, Hannes; Bergquist, Annika; Sparrelid, Ernesto SomaScan Du, Kuo. et al. Targeting senescent hepatocytes for treatment of metabolic dysfunction-associated steatotic liver disease and multi-organ dysfunction Nat Commun. Du, Kuo; Umbaugh, David S.; Liuyang, Wang; Jun, Ji Hye; Dutta, Rajesh K.; Oh, Seh Hoon; Ren, Niansheng; Zhang, Qiaojuan; Ko, Dennis C.; Ferreira, Ana; Hill, Jon; Gao, Guannan; Pullen, Steven S.; Jain, Vaibhav; Gregory, Simon; Abdelmalek, Manal F.; Diehl, Anna Mae SomaScan Yang, W. et al. Exploring new drug treatment targets for immune related bone diseases using a multi omics joint analysis strategy Sci Rep. Yang, Wei; Liu, Chenglin; Li, Zhenhua; Cui, Miao SomaScan Ghazal, R. et al. Cardiac Fibrosis in the Multi-Omics Era: Implications for Heart Failure Circ Res. Ghazal, Rachad; Wang, Min; Liu, Duan; Tschumperlin, Daniel J.; Pereira, Naveen L. SomaScan Butler, A. et al. Association of Complement Proteins with C Reactive Protein in Non-Obese Women with and Without Polycystic Ovary Syndrome Int. J. Mol. Sci. Butler, Alexandra E; Moin, Abu Saleh Md; Begam, Hamna H; Waris, Sana; Azeez, Juberiya M; Sathyapalan, Thozhukat; Atkin, Stephen L; Brennan, Edwina SomaScan Chou, C. et al. Proteostasis and lysosomal repair deficits in transdifferentiated neurons of Alzheimer’s disease Nat Cell Biol. Chou, Ching-Chieh; Vest, Ryan; Prado, Miguel A.; Wilson-Grady, Joshua; Paulo, Joao A.; Shibuya, Yohei; Moran-Losada, Patricia; Lee, Ting-Ting; Luo, Jian; Gygi, Steven P.; Kelly, Jeffery W.; Finley, Daniel; Wernig, Marius; Wyss-Coray, Tony; Frydman, Judith SomaScan Puerta, R. et al. Linking genomic and proteomic signatures to brain amyloid burden: insights from GR@ACE/DEGESCO Funct Integr Genomics. Puerta, Raquel; de Rojas, Itziar; García-González, Pablo; Olivé, Clàudia; Sotolongo-Grau, Oscar; García-Sánchez, Ainhoa; García-Gutiérrez, Fernando; Montrreal, Laura; Tartari, Juan Pablo; Sanabria, Ángela; Pytel, Vanesa; Lage, Carmen; Quintela, Inés; Aguilera, Nuria; Rodriguez-Rodriguez, Eloy; Alarcón-Martín, Emilio; Orellana, Adelina; Pastor, Pau; Pérez-Tur, Jordi; Piñol-Ripoll, Gerard; de Munain, Adolfo López; García-Alberca, Jose María; Royo, Jose Luís; Bullido, María J; Álvarez, Victoria; Real, Luis Miguel; Anchuelo, Arturo Corbatón; Gómez-Garre, Dulcenombre; Larrad, María Teresa Martínez; Franco-Macías, Emilio; Mir, Pablo; Medina, Miguel; Sánchez-Valle, Raquel; Dols-Icardo, Oriol; Sáez, María Eugenia; Carracedo, Ángel; Tárraga, Lluís; Alegret, Montse; Valero, Sergi; Marquié, Marta; Boada, Mercè; Juan, Pascual Sánchez; Cavazos, Jose Enrique; Cabrera-Socorro, Alfredo; Cano, Amanda; Ruiz, Agustín; Initiative, Alzheimer’s Disease Neuroimaging SomaScan Gagnon, E. et al. Remnant cholesterol concentrations best explain the cardiovascular benefit of APOC3 genetic inhibition: a drug target Mendelian randomization study Eur Heart J Open. Gagnon, Eloi; Gill, Dipender; Burgess, Stephen; Arsenault, Benoit J SomaScan Jonsdottir, A. et al. Missense variants in FRS3 affect body mass index in populations of diverse ancestries Nat Commun. Jonsdottir, Andrea B; Sveinbjornsson, Gardar; Thorolfsdottir, Rosa B; Tamlander, Max; Tragante, Vinicius; Olafsdottir, Thorhildur; Rognvaldsson, Solvi; Sigurdsson, Asgeir; Eggertsson, Hannes P; Aegisdottir, Hildur M; Arnar, David O; Banasik, Karina; Beyter, Doruk; Bjarnason, Ragnar G; Bjornsdottir, Gyda; Brunak, Søren; Bruun, Mie Topholm; Dowsett, Joseph; Einarsson, Eythor; Einarsson, Gudmundur; Erikstrup, Christian; Fridriksdottir, Run; Ghouse, Jonas; Gretarsdottir, Solveig; Halldorsson, Gisli H; Hansen, Torben; Helgadottir, Anna; Holm, Peter C; Ivarsdottir, Erna V; Iversen, Kasper Karmark; Jensen, Bitten Aagaard; Jonsdottir, Ingileif; Knight, Stacey; Knowlton, Kirk U; Kristmundsdottir, Snaedis; Larusdottir, Adalheidur E; Magnusson, Olafur Th; Masson, Gisli; Melsted, Pall; Mikkelsen, Christina; Moore, Kristjan H S; Oddsson, Asmundur; Olason, Pall I; Palsson, Frosti; Pedersen, Ole Birger; Schwinn, Michael; Sigurdsson, Emil L; Skaftason, Aron; Stefansdottir, Lilja; Stefansson, Hreinn; Steingrimsdottir, Thora; Sturluson, Arni; Styrkarsdottir, Unnur; Sørensen, Erik; Teitsdottir, Unnur D; Thorgeirsson, Thorgeir E; Thorisson, Gudmundur A; Thorsteinsdottir, Unnur; Ulfarsson, Magnus O; Ullum, Henrik; Vikingsson, Arnor; Walters, G Bragi; Consortium, DBDS Genomic; Jensen, Bitten Aagaard; Nadauld, Lincoln D; Bundgaard, Henning; Ostrowski, Sisse Rye; Helgason, Agnar; Halldorsson, Bjarni V; Norddahl, Gudmundur L; Ripatti, Samuli; Gudbjartsson, Daniel F; Thorleifsson, Gudmar; Steinthorsdottir, Valgerdur; Holm, Hilma; Sulem, Patrick; Stefansson, Kari SomaScan Riviere-Cazaux, C. et al. A field resource for the glioma cerebrospinal fluid proteome: impacts of resection and location on biomarker discovery Neuro Oncol. Riviere-Cazaux, Cecile; Graser, Christopher J; Warrington, Arthur E; Hoplin, Matthew D; Andersen, Katherine M; Malik, Noor; Palmer, Elizabeth A; Carlstrom, Lucas P; Dasari, Surendra; Munoz-Casabella, Amanda; Ikram, Samar; Ghadimi, Keyvan; Himes, Benjamin T; Jusue-Torres, Ignacio; Sarkaria, Jann N; Meyer, Fredric B; Van Gompel, Jamie J; Kizilbash, Sani H; Sener, Ugur; Michor, Franziska; Campian, Jian L; Parney, Ian F; Burns, Terry C SomaScan Liang, Y. et al. Circulating Proteomic Profiles Are Associated With Incident Type 2 Diabetes in Asian Populations J Clin Endocrinol Metab. Liang, Yujian; Lim, Charlie G Y; Ritchie, Scott C; Bertin, Nicolas; Chai, Jin-Fang; Yao, Jiali; Li, Yun; Tai, E Shyong; van Dam, Rob M; Sim, Xueling SomaScan Duggan, MR. et al. The Dementia SomaSignal Test (dSST): A plasma proteomic predictor of 20-year dementia risk Alzheimers Dement Duggan, Michael R.; Paterson, Clare; Lu, Yifei; Biegel, Hannah; Dark, Heather E.; Cordon, Jenifer; Bilgel, Murat; Kaneko, Naoto; Shibayama, Masaki; Kato, Shintaro; Furuichi, Makio; Waga, Iwao; Hiraga, Keita; Katsuno, Masahisa; Nishita, Yukiko; Otsuka, Rei; Davatzikos, Christos; Erus, Guray; Loupy, Kelsey; Simpson, Melissa; Lewis, Alexandria; Moghekar, Abhay; Palta, Priya; Gottesman, Rebecca F.; Resnick, Susan M.; Coresh, Josef; Williams, Stephen A.; Walker, Keenan A. SomaScan Yousif, G. et al. Distinctive blood and salivary proteomics signatures in Qatari individuals at high risk for cardiovascular disease Sci Rep. Yousif, Ghada; Murugesan, Selvasankar; Djekidel, Mohamed Nadhir; Terranegra, Annalisa; Gentilcore, Giusy; Grivel, Jean Charles; Khodor, Souhaila Al SomaScan Xu, D. et al. Identifying novel drug targets for calcific aortic valve disease through Mendelian randomization Atherosclerosis. Xu, Dilin; Lu, Jin; Yang, Yanfang; Hu, Wangxing; Chen, Jinyong; Xue, Junhui; Yang, Shuangshuang; Cao, Naifang; Hu, Haochang; Qian, Ningjing; Zhou, Dao; Dai, Hanyi; Wang, Jian'an; Liu, Xianbao SomaScan Andersen, R. et al. A genome-wide association meta-analysis links hidradenitis suppurativa to common and rare sequence variants causing disruption of the Notch and Wnt/β-catenin signaling pathways J Am Acad Dermatol. Andersen, R Kjærsgaard; Stefansdottir, L.; Riis, P Theut; Halldorsson, Gh; Ferkingstad, E.; Oddsson, A.; Walters, G.B.; Olafsdottir, Thorunn A.; Rutsdottir, G.; Zachariae, C.; Thomsen, S.F.; Brodersen, T.; Dinh, K.M.; Knowlton, K.U.; Knight, S.; Nadauld, L.D.; Banasik, K.; Brunak, S.; Hansen, T.F.; Hjalgrim, H.; Sørensen, E.; Mikkelsen, C.; Ullum, H.; Nyegaard, M.; Bruun, M.T.; Erikstrup, C.; Ostrowski, S.R.; Eidsmo, L.; Saunte, D.M.L.; Sigurgeirsson, B.; Orvar, K.B.; Saemundsdottir, J.; Melsted, P.; Norddahl, G.L.; Sulem, P.; Stefansson, H.; Holm, H.; Gudbjartsson, D.; Thorleifsson, G.; Jonsdottir, I.; Pedersen, O.B.V.; Jemec, G.B.E.; Stefansson, K. SomaScan Gaudilliere, B. et al. Infusion of young donor plasma components in older patients modifies the immune and inflammatory response to surgical tissue injury: a randomized clinical trial J. Transl. Med. Gaudilliere, Brice; Xue, Lei; Tsai, Amy S.; Gao, Xiaoxiao; McAllister, Tiffany N.; Tingle, Martha; Porras, Gladys; Feinstein, Igor; Feyaerts, Dorien; Verdonk, Franck; Sabayev, Maximilian; Hedou, Julien; Ganio, Edward A.; Berson, Eloïse; Becker, Martin; Espinosa, Camilo; Kim, Yeasul; Lehallier, Benoit; Rawner, Esther; Feng, Chunmiao; Amanatullah, Derek F.; Huddleston, James I.; Goodman, Stuart B.; Aghaeepour, Nima; Angst, Martin S. SomaScan Aldisi, R. et al. Identification of novel proteomic biomarkers for hypertension: a targeted approach for precision medicine Clin. Proteom. Aldisi, Rana S.; Alsamman, Alsamman M.; Krawitz, Peter; Maj, Carlo; Zayed, Hatem SomaScan Shaojie, F. et al. Investigating the role of gut microbiota in diabetic nephropathy through plasma proteome mediated analysis Sci Rep. Fu, Shaojie; Li, Fan; Yu, Jinyu; Ma, Shengjie; Zhang, Li; Cheng, Yanli SomaScan Wang, G. et al. Multiomics and Systematic Analyses Reveal the Roles of Hemoglobin and the HIF-1 Pathway in Polycystic Ovary Syndrome Adv Sci (Weinh). Wang, Guiquan; Mao, Weian; Zhang, Yurong; Yang, Haiyan; Zhu, Ming; Li, Yan; Chen, Wei; Chen, Yi; Lou, Chen; Li, Ping; Chang, Hsun‐Ming; Yuan, Shuai; Zhao, Yue; Mu, Liangshan SomaScan Raveendran, J. et al. Emerging trends in the cystatin C sensing technologies: towards better chronic kidney disease management RSC Adv. Raveendran, Jeethu; Gangadharan, Dhanya; Bayry, Jagadeesh; Rasheed, P. Abdul SomaScan Lee, W. et al. From Local to Systemic: The Journey of Tick Bite Biomarkers in Australian Patients Int. J. Mol. Sci. Lee, Wenna; Barbosa, Amanda D; Lee, Amy Huey-Yi; Currie, Andrew; Martino, David; Stenos, John; Long, Michelle; Beaman, Miles; Harvey, Nathan T; Kresoje, Nina; Skut, Patrycja; Irwin, Peter J; Kumarasinghe, Prasad; Hall, Roy A; Ben-Othman, Rym; Graves, Stephen; Kollmann, Tobias R; Oskam, Charlotte L SomaScan Wang,B. et al. Comparative studies of plasma proteins measured by two affinity-based platforms in Chinese adults Nat Commun. Wang, Baihan; Pozarickij, Alfred; Mazidi, Mohsen; Wright, Neil; Yao, Pang; Said, Saredo; Iona, Andri; Kartsonaki, Christiana; Fry, Hannah; Lin, Kuang; Chen, Yiping; Du, Huaidong; Avery, Daniel; Schmidt-Valle, Dan; Yu, Canqing; Sun, Dianjianyi; Lv, Jun; Hill, Michael; Li, Liming; Bennett, Derrick A.; Collins, Rory; Walters, Robin G.; Clarke, Robert; Millwood, Iona Y.; Chen, Zhengming; Wang, Baihan; Pozarickij, Alfred; Mazidi, Mohsen; Wright, Neil; Yao, Pang; Said, Saredo; Iona, Andri; Kartsonaki, Christiana; Fry, Hannah; Lin, Kuang; Chen, Yiping; Du, Huaidong; Avery, Daniel; Schmidt-Valle, Dan; Yu, Canqing; Sun, Dianjianyi; Lv, Jun; Li, Liming; Bennett, Derrick A.; Collins, Rory; Walters, Robin G.; Clarke, Robert; Millwood, Iona Y.; Chen, Zhengming SomaScan Zhang, X. et al. Mendelian Randomization and Colocalization Analysis Reveal New Drug Targets for Oral Ulcer: A Mendelian Randomization Analysis Health Sci Rep. Zhang, Xiaoyu; Fan, Hui; Zhang, Xiaoguang; Wang, Yanni; Chen, Guozhong SomaScan Rao, JH. et al. Plasma proteins mediate the effects of the gut microbiota on the development of head and neck cancer: a two-sample and mediated Mendelian randomized study Discov Oncol. Rao, Jin-Hui; Zhang, Wen-Da; Zha, Cheng-Peng; Zhang, Min-Yue; Xing, Yu-Jie; Wang, Zai-Hui; Yu, Jun-Xian; He, Dong-Yan; Sun, Chuan-Zheng; Li, Lei SomaScan Mika, K. et al. Proteomic organ-specific ageing signatures and 20-year risk of age-related diseases: the Whitehall II observational cohort study The Lancet Digital Health Kivimäki, Mika; Frank, Philipp; Pentti, Jaana; Jokela, Markus; Nyberg, Solja T; Blake, Acer; Lindbohm, Joni V; Oh, Hamilton Se-Hwee; Singh-Manoux, Archana; Wyss-Coray, Tony; Partridge, Linda SomaScan Aboelsaad, I . et al. Hepcidin, incident heart failure, and cardiac dysfunction in older adults: the ARIC study Eur J Prev Cardiol. Aboelsaad, Iman A F; Claggett, Brian L; Arthur, Victoria; Dorbala, Pranav; Matsushita, Kunihiro; Lutsey, Pamela L; Yu, Bing; Lennep, Brandon W; Ndumele, Chiadi E; Farag, Youssef M K; Shah, Amil M; Buckley, Leo F SomaScan Larsson, S. et al. Genome-wide association study and Mendelian randomization analyses reveal insights into bladder cancer etiology JNCI Cancer Spectr. Larsson, Susanna C; Chen, Jie; Ruan, Xixian; Li, Xue; Yuan, Shuai SomaScan Kemper, E. et al. Fetuin B Is Related to Cytokine/Chemokine and Insulin Signaling in Adipose Tissue and Plasma in Humans J Clin Endocrinol Metab. Kemper, Esther J; Goossens, Gijs H; Blaak, Ellen E; Adriaens, Michiel E; Meex, Ruth C R SomaScan Gao, C. et al. Proteome-Wide Association Study for Finding Druggable Targets in Progression and Onset of Parkinson's Disease CNS Neurosci Ther. Gao, Chenhao; Zhou, Haobin; Liang, Weixuan; Wen, Zhuofeng; Liao, Wanzhe; Xie, Zhixin; Liao, Cailing; He, Limin; Sun, Jingzhang; Chen, Zhilin; Li, Duopin; Yuan, Naijun; Huang, Chuiguo; Zhang, Jiewen SomaScan Ziyatdinov, A. et al. Identifying chronic obstructive pulmonary disease subtypes using multi-trait genetics EBioMedicine Ziyatdinov, Andrey; Hobbs, Brian D.; Kanaan-Izquierdo, Samir; Moll, Matthew; Sakornsakolpat, Phuwanat; Shrine, Nick; Chen, Jing; Song, Kijoung; Bowler, Russell P.; Castaldi, Peter J.; Tobin, Martin D.; Kraft, Peter; Silverman, Edwin K.; Julienne, Hanna; Cho, Michael H.; Aschard, Hugues SomaScan Wu, J. et al. Proteome-wide Mendelian randomization identifies causal plasma proteins in prostate cancer development Hum Genomics. Wu, Jian; Yang, Zitong; Ding, Jiafeng; Hao, Sida; Chen, Hong; Jin, Ke; Zhang, Cheng; Zheng, Xiangyi SomaScan Lam, J. et al. Worry Moderates Plasma Placental Growth Factor (PIGF) and Cognition in Older Adults with Amnestic Mild Cognitive Impairment (aMCI) Experimental Aging Research Lam, Jovian C.; Louras, Peter; Savettiere, Adriana; Fairchild, J. Kaci SomaScan Onsaker, A. et al. Histo-blood group ABO system transferase plasma levels and risk of future venous thromboembolism: The HUNT Study Blood. Onsaker, Asbjørn L.; Arntzen, Anna Y.; Trégouët, David-Alexandre; Nøst, Therese H.; Tang, Weighing; Guan, Weihua; Jonasson, Christian; Morange, Pierre-Emmanuel; Hinderg, Kristian D.; Folsom, Aaron R.; Hveem, Kristian; Morelli, Vânia M.; Hansen, John-Bjarne SomaScan Andresen, I. et al. Prediction of late-onset preeclampsia using plasma proteomics: a longitudinal multi-cohort study Sci Rep. Ina J Andresen, Manuela Zucknick, Maren-Helene L Degnes, Martin S Angst, Nima Aghaeepour, Roberto Romero, Marie Cecilie P Roland, Adi L Tarca, Ane Cecilie Westerberg, Trond M Michelsen  SomaScan Butler, AE. et al. Matrix Metalloproteinases, Tissue Inhibitors of Metalloproteinases, and Their Ratios in Women with Polycystic Ovary Syndrome and Healthy Controls Int. J. Mol. Sci. Alexandra E Butler, Manjula Nandakumar, Thozhukat Sathyapalan, Edwina Brennan, Stephen L Atkin SomaScan Maretty, L. et al. Proteomic changes upon treatment with semaglutide in individuals with obesity Nat Med. Lasse Maretty, Dipender Gill, Lotte Simonsen, Keng Soh, Loukas Zagkos, Michael Galanakis, Jonas Sibbesen, Miquel Triana Iglesias, Anna Secher, Dirk Valkenborg, Jonathan Q. Purnell, Lotte Bjerre Knudsen, Abd A. Tahrani, Milan Geybels SomaScan Puerta, R. et al. Head-to-Head Comparison of Aptamer- and Antibody-Based Proteomic Platforms in Human Cerebrospinal Fluid Samples from a Real-World Memory Clinic Cohort Int. J. Mol. Sci. Raquel Puerta, Amanda Cano, Pablo García-González, Fernando García-Gutiérrez, Maria Capdevila, Itziar de Rojas, Clàudia Olivé, Josep Blázquez-Folch, Oscar Sotolongo-Grau, Andrea Miguel, Laura Montrreal, Pamela Martino-Adami, Asif Khan, Adelina Orellana, Yun Ju Sung, Ruth Frikke-Schmidt, Natalie Marchant, Jean Charles Lambert, Maitée Rosende-Roca, Montserrat Alegret, Maria Victoria Fernández, Marta Marquié, Sergi Valero, Lluís Tárraga, Carlos Cruchaga, Alfredo Ramírez, Mercè Boada, Bart Smets, Alfredo Cabrera-Socorro, Agustín Ruiz SomaScan Yang, W. et al. Gut microbiota and blood biomarkers in IBD-Related arthritis: insights from mendelian randomization Commun Biol. Wei Yang, Miao Cui, Peng Yang, Chenlin Liu, Xiuzhen Han, Wenyi Yao, Zhenhua Li SomaScan Bosticardo, M. et al. Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature Sci Immunol. Marita Bosticardo, Kerry Dobbs, Ottavia M Delmonte, Andrew J Martins, Francesca Pala, Tomoki Kawai, Heather Kenney, Gloria Magro, Lindsey B Rosen, Yasuhiro Yamazaki, Hsin-Hui Yu, Enrica Calzoni, Yu Nee Lee, Can Liu, Jennifer Stoddard, Julie Niemela, Danielle Fink, Riccardo Castagnoli, Meredith Ramba, Aristine Cheng, Deanna Riley, Vasileios Oikonomou, Elana Shaw, Brahim Belaid, Sevgi Keles, Waleed Al-Herz, Caterina Cancrini, Cristina Cifaldi, Safa Baris, Svetlana Sharapova, Catharina Schuetz, Andrew R Gennery, Alexandra F Freeman, Raz Somech, Sharon Choo, Silvia C Giliani, Tayfun Güngör, Daniel Drozdov, Isabelle Meyts, Despina Moshous, Benedicte Neven, Roshini S Abraham, Aisha El-Marsafy, Maria Kanariou, Alejandra King, Francesco Licciardi, Mario E Cruz-Muñoz, Paolo Palma, Cecilia Poli, Mehdi Adeli, Mattia Algeri, Fayhan J Alroqi, Paul Bastard, Jenna R E Bergerson, Claire Booth, Ana Brett, Siobhan O Burns, Manish J Butte, Nurcicek Padem, M de la Morena, Ghassan Dbaibo, Suk See de Ravin, Dimana Dimitrova, Reda Djidjik, Mayra B Dorna, Cullen M Dutmer, Reem Elfeky, Fabio Facchetti, Ramsay L Fuleihan, Raif S Geha, Luis I Gonzalez-Granado, Liis Haljasmägi, Hanadys Ale, Anthony Hayward, Anna M Hifanova, Winnie Ip, Blanka Kaplan, Neena Kapoor, Elif Karakoc-Aydiner, Jaanika Kärner, Michael D Keller, Blachy J Dávila Saldaña, Ayça Kiykim, Taco W Kuijpers, Elena E Kuznetsova, Elena A Latysheva, Jennifer W Leiding, Franco Locatelli, Guisela Alva-Lozada, Christine McCusker, Fatih Celmeli, Megan Morsheimer, Ahmet Ozen, Nima Parvaneh, Srdjan Pasic, Alessandro Plebani, Kahn Preece, Susan Prockop, Inga S Sakovich, Elena E Starkova, Troy Torgerson, James Verbsky, Jolan E Walter, Brant Ward, Elizabeth L Wisner, Deborah Draper, Katherine Myint-Hpu, Pooi M Truong, Michail S Lionakis, Morgan B Similuk, Centralized Sequencing Program Group§§, Magdalena A Walkiewicz, Amy Klion, Steven M Holland, Cihan Oguz, Dusan Bogunovic, Kai Kisand, Helen C Su, John S Tsang, Douglas Kuhns, Anna Villa, Sergio D Rosenzweig, Stefania Pittaluga, Luigi D Notarangelo, Rajarshi Ghosh, Bryce Siefert, Mari Tokita, Jia Yan, Colleen Jodarski, Mike Kamen, Rachel Gore, Nadjalisse Reynolds-Lallement, Katie Lewis, Sarah Bannon, Adrienne Borges, Nicole Gentile SomaScan Heinken, A. et al. Systemic regulation of retinal medium-chain fatty acid oxidation repletes TCA cycle flux in oxygen-induced retinopathy Commun Biol. Almut Heinken, John M. Asara, Gopalan Gnanaguru, Charandeep Singh SomaScan Li, D. et al. The association of high-density lipoprotein cargo proteins with brain volume in older adults in the Atherosclerosis Risk in Communities (ARIC) J Alzheimers Dis. Danni Li, Binchong An, Lu Men, Matthew Glittenberg, Pamela L Lutsey, Michelle M Mielke, Fang Yu, Ron C Hoogeveen, Rebecca Gottesman, Lin Zhang, Michelle Meyer, Kevin Sullivan, Nicole Zantek, Alvaro Alonso, Keenan A Walker SomaScan Ramalingam, P. et al. Suppression of thrombospondin-1–mediated inflammaging prolongs hematopoietic health span Sci Immunol. Pradeep Ramalingam, Michael C. Gutkin, Michael G. Poulos, Agatha Winiarski, Arianna Smith, Cody Carter, Chelsea Doughty, Taylor Tillery, David Redmond, Ana G. Freire, Jason M. Butler SomaScan Jin, C. et al. Identification of biomarkers for chronic lymphocytic leukemia risk: a proteome-wide Mendelian randomization study Discov Oncol. Changyu Jin, Zehong Lu, Yuzhan Chen, Huijie Hu, Miao Zhou, Yanli Zhang, Guifang Ouyang, Tongyu Li, Lixia Sheng SomaScan Casaletto, KB. et al. Brain aging rejuvenation factors in adults with genetic and sporadic neurodegenerative disease Brain Commun. Kaitlin B Casaletto, Rowan Saloner, John Kornak, Adam M Staffaroni, Saul Villeda, Emily Paolillo, Anna M VandeBunte, Claire J Cadwallader, Argentina Lario Lago, Julia Webb, Coty Chen, Katya Rascovsky, Toji Miyagawa, Eliana Marisa Ramos, Joseph C Masdeu, Alexander Pantelyat, Maria Carmela Tartaglia, Andrea Bozoki, Peter S Pressman, Rosa Rademakers, Walter Kremers, Ryan Darby, Kyan Younes, Belen Pascual, Nupur Ghoshal, Maria Lapid, Ian R A Mackenzie, Jingyao Li, Ging-Yuek Robin Hsiung, Jacob N Hall, Maya V Yutsis, Irene Litvan, Victor W Henderson, Rajeev Sivasankaran, Katie Worringer, Kimiko Domoto-Reilly, Allison Synder, Joseph Loureiro, Joel H Kramer, Hilary Heuer, Leah K Forsberg, Howard J Rosen, Bradley Boeve, Julio C Rojas, Adam L Boxer SomaScan Jia, M. et al. Integrative bioinformatics approach identifies novel drug targets for hyperaldosteronism, with a focus on SHMT1 as a promising therapeutic candidate Sci Rep. Minyue Jia, Liya Lin, Hanxiao Yu, Zhichao Dong, Xin Pan, Xiaoxiao Song SomaScan Yoshiji, S. et al. Integrative proteogenomic analysis identifies COL6A3-derived endotrophin as a mediator of the effect of obesity on coronary artery disease Nat Genet. Satoshi Yoshiji, Tianyuan Lu, Guillaume Butler-Laporte, Julia Carrasco-Zanini-Sanchez, Chen-Yang Su, Yiheng Chen, Kevin Liang, Julian Daniel Sunday Willett, Shidong Wang, Darin Adra, Yann Ilboudo, Takayoshi Sasako, Satoshi Koyama, Tetsushi Nakao, Vincenzo Forgetta, Yossi Farjoun, Hugo Zeberg, Sirui Zhou, Michael Marks-Hultström, Mitchell J. Machiela, Rama Kaalia, Hesam Dashti, Melina Claussnitzer, Jason Flannick, Nicholas J. Wareham, Vincent Mooser, Nicholas J. Timpson, Claudia Langenberg, J. Brent Richards SomaScan Guo, X. et al. Unraveling the impact of blood RANKL and OPG levels on Alzheimer's disease: Independent of bone mineral density and inflammation Alzheimers Dement (N Y). Xingzhi Guo, Wenzhi Shi, Juanjuan Lu, Peng Tang, Rui Li SomaScan Guo, H. et al. Multi-omics analysis reveals novel causal pathways in psoriasis pathogenesis J Transl Med Hua Guo, Jinyang Gao, Liping Gong, Yanqing Wang SomaScan Hui, J. et al. A large-scale multi-omics polygenic risk score analysis identified candidate risk locus associated with rheumatoid arthritis Joint Bone Spine Jingni Hui, Dan He, Chen Liu, Panxing Shi, Ruixue Zhou, Meijuan Kang, Ye Liu, Yifan Gou, Bingyi Wang, Shiqiang Cheng, Xuena Yang, Chuyu Pan, Wenming Wei, Feng Zhang SomaScan Gan, S. et al. Transferrin Saturation, Serum Iron, and Ferritin in Heart Failure: Prognostic Significance and Proteomic Associations Circ Heart Fail. Sushrima Gan, Joe David Azzo, Lei Zhao, Bianca Pourmussa, Marie Joe Dib, Oday Salman, Ozgun Erten, Christina Ebert, A Mark Richards, Ali Javaheri, Douglas L Mann, Ernst Rietzschel, Payman Zamani, Vanessa van Empel, Thomas P Cappola, Julio A Chirinos SomaScan Canny, SP. et al. Proteomic Analyses in COVID-19-Associated Secondary Hemophagocytic Lymphohistiocytosis Crit Care Explor. Canny, Susan P.; Stanaway, Ian B.; Holton, Sarah E.; Mitchem, Mallorie; O’Rourke, Allison R.; Pribitzer, Stephan; Baxter, Sarah K.; Wurfel, Mark M.; Malhotra, Uma; Buckner, Jane H.; Bhatraju, Pavan K.; Morrell, Eric D.; Speake, Cate; Mikacenic, Carmen; Hamerman, Jessica A. SomaScan Cullel, N. et al. Glymphatic system clearance and Alzheimer’s disease risk: a CSF proteome-wide study Alzheimers Res Ther. Cullell, Natalia; Caruana, Giovanni; Elias-Mas, Andrea; Delgado-Sanchez, Ariane; Artero, Cristina; Buongiorno, Maria Teresa; Almería, Marta; Ray, Nicola J.; Correa, Sonia A. L.; Krupinski, Jerzy SomaScan Sun, W. et al. Exploring genetic associations and drug targets for mitochondrial proteins and schizophrenia risk Schizophrenia (Heidelb). Sun, Wenxi; Sun, Ping; Li, Jin; Yang, Qun; Tian, Qing; Yuan, Shiting; Zhang, Xueying; Chen, Peng; Li, Chuanwei; Zhang, Xiaobin SomaScan Nalwoga, A. et al. Evaluation of plasma alpha-1-antichymotrypsin as a marker for pulmonary Kaposi sarcoma Int J Cancer. Nalwoga, Angela; Jackson, Conner; Fiorillo, Suzanne; Manyeruke, Felix; Makoni, Tobias; Nyagura, Tatenda; White, Irene E.; Rapaport, Eric; Rochford, Rosemary; Borok, Margaret; Campbell, Thomas B. SomaScan Lydon, E. et al. Proteomic profiling of the local and systemic immune response to pediatric respiratory viral infections mSystems SomaScan Yao, Y. et al. Multimodal data integration to predict atrial fibrillation European Heart Journal SomaScan Mubido, EO. et al. Systemic biological mechanisms underpin poor post-discharge growth among severely wasted children with HIV Nat Commun. SomaScan Brækkan, SK. et al. The plasma proteome and risk of future venous thromboembolism - results from the HUNT study Thromb Haemost. SomaScan Chen, TK. et al. Proteomics and Incident Kidney Failure in Individuals With CKD: The African American Study of Kidney Disease and Hypertension and the Boston Kidney Biopsy Cohort Kidney Med. SomaScan Lim, CGY. et al. Plasma proteomic signatures of adiposity are associated with cardiovascular risk factors and type 2 diabetes risk in a multi-ethnic Asian population. Diabetes SomaScan Lai. M. et al. Serum protein risk stratification score for diagnostic evaluation of metabolic dysfunction-associated steatohepatitis Hepatol Commun. SomaScan Lopez-Silva, C. et al. Circulating Protein and Metabolite Correlates of Histologically Confirmed Diabetic Kidney Disease Kidney Med. SomaScan Conway, RB. et al. Plasma Proteomic Markers of Iron and Risk of Diabetes in a Cohort of African American and White American Current and Former Smokers Metab Syndr Obes. SomaScan Werge, MP. et al. Circulating and hepatic levels of growth differentiation factor 15 in patients with metabolic dysfunction-associated steatotic liver disease Hepatology Research SomaScan Stanaway, IB. et al. Urinary proteomics identifies distinct immunological profiles of sepsis associated AKI sub-phenotypes Crit Care. SomaScan Philippi, SM. et al. APOE genotype and brain amyloid are associated with changes in the plasma proteome in elderly subjects without dementia Ann Clin Transl Neurol. SomaScan Kumari, S. et al. Approaches and Challenges in Characterizing the Molecular Content of Extracellular Vesicles for Biomarker Discovery Biomolecules SomaScan Murugesan, S. et al. Microbial and proteomic signatures of type 2 diabetes in an Arab population J Transl Med. SomaScan Wu, MH. et al Proteome-wide Mendelian randomization and therapeutic targets for bladder cancer BMC Urol. SomaScan Doulamis, IP. et al. Mitochondrial transplantation normalizes transcriptomic and proteomic shift associated with ischemia reperfusion injury in neonatal hearts donated after circulatory death Sci Rep. SomaScan Smith, IC. et al. Plasma-derived protein and imaging biomarkers distinguish disease severity in oculopharyngeal muscular dystrophy Journal of Neuromuscular Diseases SomaScan Nandakumar, M. et al. Cardiovascular Risk Biomarkers in Women with and Without Polycystic Ovary Syndrome Biomolecules SomaScan Chen, S. et al. Exploring the associations of plasma proteins with frailty based on Mendelian randomization BMC Immunol. SomaScan Melano, I. et al. SARS-CoV-2 ORF8 drives osteoclastogenesis in preexisting immune-mediated inflammatory diseases JCI Insight SomaScan Byrne, A. et al. Neonates exposed to HIV but uninfected exhibit an altered gut microbiota and inflammation associated with impaired breast milk antibody function Microbiome SomaScan Maretty, L. et al. Proteomic changes upon treatment with semaglutide in individuals with obesity Nat Med. SomaScan Lumish, HS. et al. Prediction of new-onset atrial fibrillation in patients with hypertrophic cardiomyopathy using plasma proteomics profiling Europace SomaScan Hiramoto, K. et al. Urinary biomarkers associated with pathogenic pathways reflecting histological findings in lupus nephritis Arthritis Rheumatol. SomaScan Qiu, X. et al. The Biomarkers in Extreme Longevity: Insights Gained from Metabolomics and Proteomics Int J Med Sci SomaScan Moll, M. et al. Polygenic and transcriptional risk scores identify chronic obstructive pulmonary disease subtypes in the COPDGene and ECLIPSE cohort studies eBioMedicine SomaScan Lee, KH. et al. Addressing statistical challenges in the analysis of proteomics data with extremely small sample size: a simulation study BMC Genomics SomaScan Sparling, AC. et al. Neutrophil and mononuclear leukocyte pathways and upstream regulators revealed by serum proteomics of adult and juvenile dermatomyositis Arthritis Res Ther. SomaScan Alcalde-Herraiz, M. et al. Effect of genetically predicted sclerostin on cardiovascular biomarkers, risk factors, and disease outcomes Nat Commun. SomaScan Chen, Z. et al. Sodium-glucose cotransporter protein 2 inhibition, plasma proteins, and ischemic stroke: A mediation Mendelian randomization and colocalization study J Stroke Cerebrovasc Dis. SomaScan Ge, F. et al. Plasma Glutaminyl-Peptide Cyclotransferase Mediates Glucosamine-Metabolism-Driven Protection Against Hypertension: A Mendelian Randomization Study Int. J. Mol. Sci. SomaScan Anwar, MY. et al. Machine learning-based clustering identifies obesity subgroups with differential multi-omics profiles and metabolic patterns Obesity SomaScan Jiang, Q. et al. Exploring susceptibility and therapeutic targets for kidney stones through proteome-wide Mendelian randomization Hum Mol Genet. SomaScan Morató, X. et al. Associations of plasma SMOC1 and soluble IL6RA levels with the progression from mild cognitive impairment to dementia Brain, Behavior, & Immunity SomaScan Lou, J. et al. Plasma pQTL and brain eQTL integration identifies PNKP as a therapeutic target and reveals mechanistic insights into migraine pathophysiology J Headache Pain SomaScan Xiao, QA. et al. Identification of novel drug targets for liver cirrhosis and its potential side-effects by human plasma proteome Sci Rep. SomaScan Dai, T. et al. Genetic Evidence for the Causal Link Between Coagulation Factors and the Risk of Ovarian Cancer: A Two-Sample Mendelian Randomization Study International Journal of Women’s Health SomaScan Maddaloni, E. et al. Osteoprotegerin, Osteopontin, and Osteocalcin Are Associated With Cardiovascular Events in Type 2 Diabetes: Insights From EXSCEL Diabetes Care SomaScan Ji, Y. et al. Association of Coagulation Factor XI Level With Cardiovascular Events and Cardiac Function in Community-Dwelling Adults: From ARIC and CHS Circulation SomaScan Lim, CGY et al. Proteomic analysis identifies novel biological pathways that may link dietary quality to type 2 diabetes risk: evidence from African American and Asian cohorts Am J Clin Nutr. SomaScan Degnes, ML. et al. Protein biomarker signatures of preeclampsia - a longitudinal -multiplex proteomics study Sci Rep. SomaScan Chen, Y. et al. Identifying prothrombin and bone sialoprotein as potential drug targets for idiopathic pulmonary fibrosis BMC Pulm Med. SomaScan Onyango, CO. et al. Transcriptomic and Proteomic Insights into Host Immune Responses in Pediatric Severe Malarial Anemia: Dysregulation in HSP60-70-TLR2/4 Signaling and Altered Glutamine Metabolism Pathogens SomaScan Lumish, HS. et al. Comprehensive Proteomic Profiling of Human Myocardium Reveals Signaling Pathways Dysregulated in Hypertrophic Cardiomyopathy J Am Coll Cardiol. SomaScan McHill, AW. et al. Circadian misalignment disrupts biomarkers of cardiovascular disease risk and promotes a hypercoagulable state Eur J Neurosci. SomaScan Koychev, I. et al. Inflammatory proteins associated with Alzheimer's disease reduced by a GLP1 receptor agonist: a post hoc analysis of the EXSCEL randomized placebo controlled trial Alzheimers Res Ther. SomaScan Wang, S. et al. Development, characterization, and replication of proteomic aging clocks: Analysis of 2 population-based cohorts PLoS Med. SomaScan Wang, QS. et al. Statistically and functionally fine-mapped blood eQTLs and pQTLs from 1,405 humans reveal distinct regulation patterns and disease relevance Nat Genet. SomaScan Guan, H. et al. Exploring the design of clinical research studies on the efficacy mechanisms in type 2 diabetes mellitus Front Endocrinol. SomaScan Singh, A. et al. Recent developments in non-invasive methods for assessing metabolic dysfunction-associated fatty liver disease World J Gastroenterol SomaScan Tang, W. et al. Application of large‑scale and multicohort plasma proteomics datato discover novel causal proteins in gastric cancer Discov Oncol. SomaScan Zhang, Y. et al. Circulating RAC1 contributed to steroid-sensitive nephrotic syndrome: Mendelian randomization, single-cell RNA-sequencing, proteomic, and experimental evidence Ren Fail. SomaScan Bédard-Matteau, J. et al. Circulating IL-17F, but not IL-17A, is elevated in severe COVID-19 and leads to an ERK1/2 and p38 MAPK-dependent increase in ICAM-1 cell surface expression and neutrophil adhesion on endothelial cells Front. Immunol. SomaScan Ochoa-Leite, C. et al. Metabolomics and proteomics in occupational medicine: a comprehensive systematic review J Occup Med Toxicol. SomaScan Hill, C. et al. Integrated multiomic analyses: An approach to improveunderstanding of diabetic kidney disease Diabet Med. SomaScan Chen, L. et al. Systematic identification of therapeutic targets for coronary artery calcification: an integrated transcriptomic and proteomic Mendelian randomization Front. Cardiovasc. SomaScan Wang, L. et al. Clustering-aided prediction of outcomes in patients with idiopathic pulmonary fibrosis Respir Res. SomaScan Candia, J. et al. Variability of 7K and 11K SomaScan Plasma Proteomics Assays Proteome Res. SomaScan Geyer, PE. et al. The Circulating Proteome─Technological Developments,Current Challenges, and Future Trends Trends. J Proteome Res. SomaScan Long, H. et al. Preclinical and first-in-human evaluation of AL002, a novel TREM2 agonistic antibody for Alzheimer’s disease Alzheimers Res Ther. SomaScan van Vugt, M. et al. Integrating metabolomics and proteomics to identify novel drug targets for heart failure and atrial fibrillation Genome Med. SomaScan Goeminne, LJE. et al. Plasma protein-based organ-specific aging and mortality models unveil diseases as accelerated aging of organismal systems Cell Metab. SomaScan Ihara, K. et al. Circulating proteins linked to apoptosis processes and fast development of end-stage kidney disease in diabetes JCI Insight. SomaScan Liang, W. et al. An integrated multi-omics analysis reveals osteokines involved in global regulation Cell Metab. SomaScan Shen, Y. et al. CSF proteomics identifies early changes in autosomal dominant Alzheimer's disease Cell SomaScan Liu, S. et al. Identification of proteins associated with type 2 diabetes risk in diverse racial and ethnic populations Diabetologia SomaScan Moll, M. et al. A protein risk score for all-cause and respiratory-specific mortality in non-Hispanic white and African American individuals who smoke Sci Rep. SomaScan Konigsberg, IR. et al. Proteomic networks and related genetic variants associated with smoking and chronic obstructive pulmonary disease BMC Genomics SomaScan Perry, AS. et al. Clinical-transcriptional prioritization of the circulating proteome in human heart failure Cell Rep Med. SomaScan Allen, LH. et al. Multiomics: Functional Molecular Biomarkers of Micronutrients for Public Health Application Annu Rev Nutr. SomaScan Lan, T. et al. Diagnostics and omics technologies for the detection and prediction of metabolic dysfunction-associated steatotic liver disease-related malignancies Metabolism SomaScan Sproull, M. et al. Organ-specific Biodosimetry Modeling Using Proteomic Biomarkers of Radiation Exposure Radiat Res. SomaScan Salman, O. et al. Proteomic Correlates and Prognostic Significance of Kidney Injury in Heart Failure With Preserved Ejection Fraction J Am Heart Assoc. SomaScan Salman, O. et al. Prognostic Significance and Biologic Associations of Senescence-Associated Secretory Phenotype Biomarkers in Heart Failure J Am Heart Assoc. SomaScan Samorodnitsky, S. et al. Novel approach to exploring protease activity and targets in HIV-associated obstructive lung disease using combined proteomic-peptidomic analysis Respir Res. SomaScan Zhu, Y. et al. Multi-trait analysis reveals risk loci for heart failure and the shared genetic etiology with blood lipids, blood pressure, and blood glucose Cell Rep. SomaScan Julg, B. et al. Safety and antiviral effect of a triple combination of HIV-1 broadly neutralizing antibodies: a phase 1/2a trial Nat Med. SomaScan Zhou, Z. et al. Identification of novel protein biomarkers and therapeutic targets for ankylosing spondylitis using human circulating plasma proteomics and genome analysis Anal Bioanal Chem. SomaScan Zhao, J. et al. Proteomic Mendelian randomization to identify protein biomarkers of telomere length Sci Rep. SomaScan Fu, Z. et al. Hyaluronan and proteoglycan link protein 1 – A novel signaling molecule for rejuvenating aged skin Matrix Biol. SomaScan Cheng, L. et al. Evaluation of circulating plasma proteins in prostate cancer using mendelian randomization Discov Oncol. SomaScan Olafsdottir, TA. et al. Sequence variants influencing the regulation of serum IgG subclass levels Nat Commun. SomaScan Shi, K. et al. Identification of potential therapeutic targets for nonischemic cardiomyopathy in European ancestry: an integrated multiomics analysis Cardiovasc Diabetol. SomaScan Peterson, TE. et al. Proteomics of left ventricular structure in the Multi-Ethnic Study of Atherosclerosis ESC Heart Fail. SomaScan Du, S. et al. Protein Biomarkers of Ultra-Processed Food Consumption and Risk of Coronary Heart Disease, Chronic Kidney Disease, and All-Cause Mortality J Nutr. SomaScan Carrasco-Zanini, J. et al. Mapping biological influences on the human plasma proteome beyond the genome Nat Metab. SomaScan Li, J. et al. Identification of novel proteins for coronary artery disease by integrating GWAS data and human plasma proteomes Heliyon SomaScan Voordes, GHD. et al. Clinical and proteomic profiles of chronic kidney disease in heart failure with reduced and preserved ejection fraction Int J Cardiol. SomaScan Dourdouna, MM. et al. Proteomic Signatures of Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19: A Narrative Review Children SomaScan Schmidt, IM. et al. Plasma proteomics of acute tubular injury Nat Commun. SomaScan Jabalameli, MR. et al. Polygenic prediction of human longevity on the supposition of pervasive pleiotropy Sci Rep. SomaScan Wang, R. et al. Adipocyte deletion of the oxygen-sensor PHD2 sustains elevated energy expenditure at thermoneutrality Nat Commun. SomaScan Pichet Binette, A. et al. Proteomic changes in Alzheimer disease associated with progressive Aβ plaque and tau tangle pathologies Nat Neurosci. SomaScan Giro, P. et al. Proteomic Profile of the ICAM1 p.K56M HFpEF Risk Variant JACC SomaScan Kermani, NZ. et al. Endotypes of severe neutrophilic and eosinophilic asthma from multi-omics integration of U-BIOPRED sputum samples Clin Transl Med. SomaScan Doostparast Torshizi, A. et al. Proteogenomic network analysis reveals dysregulated mechanisms and potential mediators in Parkinson’s disease Nat Commun. SomaScan Marsh, TW. et al. A genetic and proteomic comparison of key AD biomarkers across tissues Alzheimers Dement. SomaScan Tripp, BA. et al. Integrated Multi-Omics Analysis of Cerebrospinal Fluid in Postoperative Delirium Biomolecules SomaScan Quesnel, MJ. et al. Osteopontin: A novel marker of pre-symptomatic sporadic Alzheimer’s disease Alzheimers Dement. SomaScan Azeze, GG. et al. Proteomics approach to discovering non-invasive diagnostic biomarkers and understanding the pathogenesis of endometriosis: a systematic review and meta-analysis J Transl Med. SomaScan Joyce, T. et al. Serum CD133-Associated Proteins Identified by Machine Learning Are Connected to Neural Development, Cancer Pathways, and 12-Month Survival in Glioblastoma Cancers SomaScan Xu, L. et al. The application of aptamers in the field of aging and age-related diseases Clin. Transl. Disc. SomaScan Gupta, S. et al. Inhibition of JAK-STAT pathway corrects salivary gland inflammation and interferon driven immune activation in Sjögren's Disease Ann Rheum Dis SomaScan Turnbull, A. et al. Age-associated proteins explain the role of medial temporal lobe networks in Alzheimer's disease Geroscience SomaScan Wolfe, KR. et al. Early Circulating Biomarkers of Language Development in Single Ventricle Heart Disease JAMA Pediatr. SomaScan Zheng, L. et al. Contrastive machine learning reveals Parkinson’s disease specific features associated with disease severity and progression Commun Biol. SomaScan Went, M. et al. Deciphering the genetics and mechanisms of predisposition to multiple myeloma Nat Commun. SomaScan Leo, S. et al. Biomarkers in diagnosing and therapeutic monitoring of tuberculosis: areview Ann Med. SomaScan Donovan, M. et al. Multimodal analysis of dysregulated heme metabolism, hypoxic signaling, and stress erythropoiesis in Down syndrome Cell Rep. SomaScan Zhan, C. et al. Proteome-Wide Mendelian Randomisation Identifies Causal Links of Plasma Proteins With Periodontitis Int Dent J. SomaScan Duggan, MR. et al. Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline Nat Aging SomaScan Beutgen, VM. et al. Secretome analysis using Affinity Proteomics and Immunoassays: a focus on Tumor Biology Mol Cell Proteomics. SomaScan Cunningham, KY. et al. Plasma proteome profiling in giant cell arteritis Ann Rheum Dis. SomaScan Liu, T. et al. Validation of candidate protein biomarkers previously identified by genetic instruments for prostate cancer risk: A prospective cohort analysis of directly measured protein levels in the ARIC study Prostate SomaScan Shen, X. et al. Nonlinear dynamics of multi-omics profiles during human aging Nature Aging SomaScan Cardiello, JF. et al. Characterizing primary transcriptional responses to short term heat shock in Down syndrome PLoS One SomaScan Ardissino, M. et al. Proteome- and Transcriptome-Wide Genetic Analysis Identifies Biological Pathways and Candidate Drug Targets for Preeclampsia Circ Genom Precis Med. SomaScan Frick, EA. et al. Serum proteomics reveal APOE-ε4-dependent and APOE-ε4-independent protein signatures in Alzheimer's disease Nat Aging SomaScan Halama, A. et al. A roadmap to the molecular human linking multiomics with population traits and diabetes subtypes Nat Commun. SomaScan Conlon, DM. et al. Genotype-First Approach Identifies an Association between rs/FOG2S657G and Liver Disease through Alterations in mTORC1 Signaling Genes SomaScan Guo, X. et al. Causal effect of blood osteocalcin on the risk of Alzheimer's disease and the mediating role of energy metabolism Transl Psychiatry. SomaScan Wang, Q. et al. Causal associations of plasma proteins with lung squamous cell carcinoma risk: a proteome-wide Mendelian randomization and colocalization analysis Clinical Cancer Bulletin SomaScan Dib, MJ. et al. Proteome-Wide Genetic Investigation of Large Artery Stiffness JACC SomaScan Maimaiti, A. et al. Gut Microbiota, Metabolites, Circulating Cytokines and Growth Factors, Plasma Proteins, and Risk of Intracranial Aneurysms: A Two-Sample Mendelian Randomization Study Acta Neurologica Scandinavica SomaScan Mckinnon, K. et al. Epigenetic scores derived in saliva are associated with gestational age at birth Clin Epigenetics SomaScan Johnson, BS. et al. Targeted degradation of extracellular mitochondrial aspartyl -tRNA synthetase modulates immune responses Nat Commun. SomaScan Sivakumar, P. et al. SomaLogic proteomics reveals new biomarkers and providesmechanistic, clinical insights into Acetyl coA Carboxylase (ACC) inhibition in Non-alcoholic Steatohepatitis (NASH) Sci Rep. SomaScan Petersen, TB. et al. Proteomic biomarkers related to obesity in heart failure with reduced ejection fraction and their associations with outcome Obesity (Silver Spring) SomaScan Kraemer, S. et al. Crossing the Halfway Point: Aptamer-Based, Highly Multiplexed Assay for the Assessment of the Proteome J Proteome Res. SomaScan Cannon, EJ. et al. Anemia, Iron Deficiency, and Cause-Specific Mortality: The Atherosclerosis Risk in Communities (ARIC) Study Gerontology SomaScan Juliar, BA. et al. Interferon-γ induces combined pyroptotic angiopathy and APOL1 expression in human kidney disease Cell Rep. SomaScan Li, S. et al. Association between plasma proteome and pulmonary heart disease: A two-stage Mendelian randomization analysis Clin Respir J. SomaScan Perry, AS. et al. Proteomic analysis of cardiorespiratory fitness for prediction of mortality and multisystem disease risks Nat Med. SomaScan Mostafa, I. et al. A microbiota-directed complementary food intervention in 12-18-month-old Bangladeshi children improves linear growth EBioMedicine SomaScan Warren, G. et al. Discovery and Preclinical Evaluation of a Novel Inhibitor of FABP5, ART26.12, Effective in Oxaliplatin-Induced Peripheral Neuropathy J. Pain SomaScan Nandakumar, M. et al. A Cross-Sectional Exploratory Study of Cardiovascular Risk Biomarkers in Non-Obese Women with and without Polycystic Ovary Syndrome: Association with Vitamin D Int. J. Mol. Sci. SomaScan Mi, Y. et al. High-throughput mass spectrometry maps the sepsis plasma proteome and differences in patient response Sci Transl Med. SomaScan Troisi, R. et al. Structural overview of DNA and RNA G-quadruplexes in their interaction with proteins Curr Opin Struct Biol. SomaScan Liu, F. et al. Mid-life plasma proteins associated with late-life prefrailty and frailty: a proteomic analysis Geroscience SomaScan Rao, P. et al. Plasma Proteomics of Exercise Blood Pressure and Incident Hypertension JAMA Cardiol. SomaScan Daghlas, I. et al. Mechanisms of Hypercoagulability Driving Stroke Risk in Obesity: A Mendelian Randomization Study Neurology SomaScan Lopez, L. et al. Comparative Analysis of Protein Quantification by the SomaScan Assay versus Orthogonal Methods in Urine from People with Diabetic Kidney Disease J. Proteome Res. SomaScan Si, S. et al. Identification of novel therapeutic targets for chronic kidney disease and kidney function by integrating multi-omics proteome with transcriptome Genome Med. SomaScan Kraaijenhof, JM. et al. Proteomic Signatures of Genetically Predicted and Pharmacologically Observed PCSK9 Inhibition J Am Heart Assoc. SomaScan Patel-Murray, N. et al. Aptamer Proteomics for Biomarker Discovery in Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Proteomic Substudy J Am Heart Assoc. SomaScan Sun, BB. et al. Promises and challenges of populational proteomics in health and disease Mol Cell Proteomics SomaScan Ryden, M. et al. Exploring the early molecular pathogenesis of osteoarthritis using differential network analysis of human synovial fluid Mol Cell Proteomics SomaScan Nguyen, GY. et al. Matrix metalloproteinase 9: an emerging biomarker for classification of adherent vestibular schwannoma Neurooncol Adv. SomaScan Dammer, EB. et al. Proteomic analysis of Alzheimer's disease cerebrospinal fluid reveals alterations associated with APOE ε4 and atomoxetine treatment Sci Transl Med. SomaScan Kim, H. et al. An Early Gestation Plasma Inflammasome in Rural Bangladeshi Women Biomolecules SomaScan Yang, H. et al. Plasma proteome mediate the impact of PM2.5 on stroke: A 2-step Mendelian randomization study Ecotoxicol Environ Saf. SomaScan Yusri, K. et al. Towards Healthy Longevity: Comprehensive Insights from Molecular Targets and Biomarkers to Biological Clocks Int J Mol Sci. SomaScan Niu, PP. et al. Identifying novel proteins for migraine by integrating proteomes from blood and CSF with genome-wide association data CNS Neurosci Ther. SomaScan Donovan, M. et al. Variegated overexpression of chromosome 21 genes reveals molecular and immune subtypes of Down syndrome Nat Commun. SomaScan Milbourn, H. et al. Generation Scotland: an update on Scotland's longitudinal family health study BMJ Open SomaScan de Klerk, JA. et al. Circulating small non-coding RNAs are associated with the insulin-resistant and obesity-related type 2 diabetes clusters Diabetes Obes Metab. SomaScan Saevarsdottir, S. et al. Start codon variant in LAG3 is associated with decreased LAG-3 expression and increased risk of autoimmune thyroid disease Nat Commun. SomaScan Liu, X. et al. Exploring potential plasma drug targets for cholelithiasis through multiancestry Mendelian randomization Int J Surg. SomaScan Andrzejczyk, K. et al. Identifying plasma proteomic signatures from health to heart failure, across the ejection fraction spectrum Sci Rep. SomaScan Duggan, M. et al. Proteome-wide analysis identifies plasma immune regulators of amyloid-beta progression Brain Behav Immun. SomaScan Guo ,Y. et al. Multiplex cerebrospinal fluid proteomics identifies biomarkers for diagnosis and prediction of Alzheimer's disease Nat Hum Behav. SomaScan Wise, A. et al. CSF Proteomics in Patients With Progressive Supranuclear Palsy Neurology SomaScan Greenland, P. et al. Large-Scale Proteomics in Early Pregnancy and Hypertensive Disorders of Pregnancy JAMA Cardiol. SomaScan Schmidt, AF. et al. Genetic evidence for serum amyloid P component as a drug target in neurodegenerative disorders Open Biol. SomaScan Li, Y. et al. Multicenter proteome-wide Mendelian randomization study identifies causal plasma proteins in melanoma and non-melanoma skin cancers Commun Biol. SomaScan Fernandez, MV. et al. Genetic and multi-omic resources for Alzheimer disease and related dementia from the Knight Alzheimer Disease Research Center Sci Data. SomaScan Mckinnon, K. et al. Epigenetic scores derived in saliva are associated with gestational age at birth Clin Epigenetics SomaScan Ashmar, SA. et al. Proteomic Analysis of Prehypertensive and Hypertensive Patients: Exploring the Role of the Actin Cytoskeleton Int. J. Mol. Sci. SomaScan Butler, AE. et al. A Cross-Sectional Study of Glomerular Hyperfiltration in Polycystic Ovary Syndrome Int. J. Mol. Sci. SomaScan Smith-Byrne, K. et al. Identifying therapeutic targets for cancer among circulating proteins and risk of nine cancers Nat Commun. SomaScan Zhang, X. et al. Pre-diagnostic plasma proteomics profile for hepatocellular carcinoma J Natl Cancer Inst. SomaScan Sproull, M. et al. Comparison of Novel Proteomic Expression Profiles for Radiation Exposure in Male and Female C57BL6 Mice Radiat Res. SomaScan Eteleeb, AM. et al. Brain high-throughput multi-omics data reveal molecular heterogeneity in Alzheimer’s disease PLoS Biol. SomaScan Akenroye, A. et al. Ratio of plasma IL-13/TNF- ∝ and CXCL10/CCL17 predicts mepolizumab and omalizumab response in asthma better than eosinophil count or immunoglobulin E level Sci Rep. SomaScan Beutgen, V. et al. Advances in aqueous humor proteomics for biomarker discovery and disease mechanisms exploration: a spotlight on primary open angle glaucoma Front Mol Neurosci. SomaScan Peng, Y. et al. Noninvasive Diagnostic Methods in Liver Cirrhosis Book Chapter SomaScan Sun, Y. et al. The Effect of Histo-Blood Group ABO System Transferase (BGAT) on Pregnancy Related Outcomes：A Mendelian Randomization Study Comput Struct Biotechnol J. SomaScan Dubin, RF. et al. Incident heart failure in chronic kidney disease: proteomics informs biology and risk stratification Eur Heart J. SomaScan Thiele, M. et la. Opportunities and barriers for omics-based biomarker discovery in steatotic liver diseases J Hepatol. SomaScan Westerberg, AC. et al. Angiogenic and vasoactive proteins in the maternal-fetal interface in healthy pregnancies and preeclampsia Am J Obstet Gynecol. SomaScan Gómez-Pascual, A. et al. Paired plasma lipidomics and proteomics analysis in the conversion from mild cognitive impairment to Alzheimer's disease Comput Biol Med. SomaScan Reznichenko, A. et al. Unbiased kidney-centric molecular categorization of chronic kidney disease as a step towards precision medicine Kidney Int. SomaScan Cao, Z. et al. Identification of plasma protein markers of allergic disease risk: a mendelian randomization approach to proteomic analysis Genomics SomaScan Nandakumar, M. et al. Effect of Hypoglycemia and Rebound Hyperglycemia on Proteomic Cardiovascular Risk Biomarkers Biomedicines SomaScan Guo, X. et al. Causal effect of blood osteocalcin on the risk of Alzheimer’s disease and the mediating role of energy metabolism Transl Psychiatry SomaScan Kim, T. et al. Aptamer-Based Proteomics in CKD Am J Kidney Dis. SomaScan Li, J. et al. Proteome-wide Mendelian randomization identifies potential therapeutic targets for nonalcoholic fatty liver diseases Sci Rep. SomaScan Ramonfaur, D. et al. High Throughput Plasma Proteomics and Risk of Heart Failure and Frailty in Late Life JAMA Cardiol. SomaScan Kim, T. et al. Plasma Proteins Associated with Chronic Histopathologic Lesions on Kidney Biopsy J Am Soc Nephrol. SomaScan Hart, LM. et al. Small RNA sequencing reveals snoRNAs and piRNA- as novel players in diabetic kidney disease Endocrine SomaScan Austin, TR. et al. A plasma protein-based risk score to predict hip fractures Nat Aging SomaScan Zhu, Y. et al. Identification of pleiotropic and specific therapeutic targets for cardio-cerebral diseases: A large-scale proteome-wide mendelian randomization and colocalization study PLoS One SomaScan Kim, H. et al. Multimodal Reinforcement Learning for Embedding Networks and Medication Recommendation in Parkinson’s Disease IEEE Xplore SomaScan Beutgen, V. et al. Sample-Treatment with the Virucidal β-Propiolactone Does Not Preclude Analysis by Large Panel Affinity Proteomics, Including the Discovery of Biomarker Candidates Anal Chem. SomaScan Beenken, A. et al. Blood Proteomics for Biomarkers of Kidney Pathology J Am Soc Nephrol. SomaScan Shi, L. et al. APOB and CCL17 as Mediators in the Protective Effect of SGLT2 Inhibition against Myocardial Infarction: Insights from Proteome-wide Mendelian Randomization Eur J Pharmacol. SomaScan Shue, F. et al. CSF biomarkers of immune activation and Alzheimer's disease for predicting cognitive impairment risk in the elderly Sci Adv. SomaScan Tasci, E. et al. MGMT ProFWise: Unlocking a New Application for Combined Feature Selection and the Rank-Based Weighting Method to Link MGMT Methylation Status to Serum Protein Expression in Patients with Glioblastoma Int. J. Mol. Sci. SomaScan Wang, H. et al. Identification of potential drug targets for allergic diseases from a genetic perspective: A mendelian randomization study Clin Transl Allergy. SomaScan Mao, R. et al. Identification of prospective aging drug targets via Mendelian randomization analysis Aging Cell SomaScan Kamar, SA. et al. The plasma proteome is linked with left ventricular and left atrial function parameters in patients with chronic heart failure Eur Heart J Cardiovasc Imaging. SomaScan Timsina, J. et al. Blood-Based Proteomics for Adult-Onset Focal Dystonias Ann Neurol. SomaScan Suryadevara, R. et al. Blood-based Transcriptomic and Proteomic Biomarkers of Emphysema Am J Respir Crit Care Med. SomaScan Bu, S. et al. Proteomics validate circulating GDF-15 as an independent biomarker for COVID-19 severity Front. Immunol. Sec. Viral Immunology SomaScan Yi, H. et al. TOPMed imputed genomics enhances genomic atlas of the human proteome in brain, cerebrospinal fluid, and plasma Sci Data SomaScan Barros, O. et al. Shaping the future of oral cancer diagnosis: advances in salivary proteomics Expert Rev Proteomics SomaScan Coorsen, J. et al. Proteomics—The State of the Field † Proteomes SomaScan Wang, W. et al. Relationship between plasma brain-derived neurotrophic factor levels and neurological disorders: An investigation using Mendelian randomisation Heliyon SomaScan Specht, A. et al. Circadian protein expression patterns in healthy young adults Sleep Health SomaScan Perry, AS. et al. Proteomics, Human Environmental Exposure, and Cardiometabolic Risk Circ Res. SomaScan Qin, S. et al. Mendelian randomization of circulating proteome identifies IFN-γ as a druggable target in aplastic anemia Ann Hematol SomaScan Møller, PL. et al. Predicting the presence of coronary plaques featuring high-risk characteristics using polygenic risk scores and targeted proteomics in patients with suspected coronary artery disease Genome Med. SomaScan Li, J. et al. Integrative multi-omics analysis identifies genetically supported druggable targets and immune cell specificity for myasthenia gravis J Transl Med. SomaScan Deng, M. et al. Characterization of sexual dimorphism in ANGPTL4 levels and function J Lipid Res. SomaScan Wilson, EN. et al. TREM1 disrupts myeloid bioenergetics and cognitive function in aging and Alzheimer disease mouse models Nat Neurosci. SomaScan Passaro, A. et al. Cancer biomarkers: Emerging trends and clinical implications for personalized treatment Cell SomaScan Rai, MF. et al. Three decades of advancements in osteoarthritis research: insights from transcriptomic, proteomic, and metabolomic studies Osteoarthritis Cartilage SomaScan Karvelas, N. et al. Enlarged perivascular spaces are associated with white matter injury, cognition and inflammation in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy Brain Commun. SomaScan Lee, C. et al. Signaling Pathways Associated with Prior Cardiovascular Events in Hypertrophic Cardiomyopathy J Card Fail. SomaScan Aurora, L. et al. Signaling Pathways in Hypertrophic Cardiomyopathy: Will Proteomic Profiling Guide the Future? J Card Fail. SomaScan Sasamoto, N. et al. Plasma proteins and persistent post-surgical pelvic pain among adolescents and young adults with endometriosis Am J Obstet Gynecol. SomaScan Christopoulos, P. et al. Plasma Proteome-Based Test for First-Line Treatment Selection in Metastatic Non-Small Cell Lung Cancer JCO Precis Oncol. SomaScan Dorian, D. et al. Exercise‐Dependent Modulation of Immunological Response Pathways in Endurance Athletes With and Without Atrial Fibrillation J Am Heart Assoc. SomaScan Chai, RC. et al. The potential of the proteome to predict fracture J Bone Miner Res. SomaScan Wang, S. et al. Accelerated Aging in Cancer Survivors: Cellular Senescence, Frailty, and Possible Opportunities for Interventions Int. J. Mol. Sci. SomaScan Liu, X. et al. Plasma proteomic signature of human longevity Aging Cell SomaScan Sathyan, S. et al. Plasma proteomic profile of abdominal obesity in older adults, Plasma proteomic profile of abdominal obesity in older adults Obesity (Silver Spring) SomaScan Casanova, R. et al. Associations of plasma proteomics and age-related outcomes with brain age in a diverse cohort Geroscience SomaScan Koureta, E. et al. Evolving role of semaglutide in NAFLD: in combination, weekly and oral administration Front. Pharmacol. SomaScan Saint-André, V. et al. Smoking changes adaptive immunity with persistent effects Nature SomaScan Suhre, K. et al. Nanoparticle enrichment mass-spectrometry proteomics identifies protein-altering variants for precise pQTL mapping Nat Commun. SomaScan Mohammadi, H. et al. Which neuroimaging and fluid biomarkers method is better in theranostic of Alzheimer’s disease? An umbrella review IBRO Neuroscience Reports SomaScan Aboelsaad IAF. et al. Plasma Ferritin Levels, Incident Heart Failure, and Cardiac Structure and Function: The ARIC Study JACC Heart Fail. SomaScan Altieri, A. et al. Human host defence peptide LL-37 suppresses TNFα- mediated matrix metalloproteinases MMP9 and MMP13, in human bronchial epithelial cells J Innate Immun. SomaScan Rutledge, J. et al. Comprehensive proteomics of CSF, plasma, and urine identify DDC and other biomarkers of early Parkinson's disease Acta Neuropathol. SomaScan Li, D. et al. Multi-omics Analyses Identify AKR1A1 as a Biomarker for Diabetic Kidney Disease Diabetes SomaScan Diakos, NA. et al. Circulating Proteome Analysis Identifies Reduced Inflammation After Initiation of Hemodynamic Support with Either Veno-Arterial Extracorporeal Membrane Oxygenation or Impella in Patients with Cardiogenic Shock J Cardiovasc Transl Res. SomaScan Dib, MJ. et al. Proteomic Associations of Adverse Outcomes in Human Heart Failure J Am Heart Assoc. SomaScan Lin, L. et al.  Proteome-wide mendelian randomization investigates potential associations in heart failure and its etiology: emphasis on PCSK9 BMC Med Genomics SomaScan Walitt, B. et al.  Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome Nat Commun. SomaScan Zagkos, L. et al.  Genetic investigation into the broad health implications of caffeine: evidence from phenome-wide, proteome-wide and metabolome-wide Mendelian randomization BMC Med. SomaScan Slieker, RC. et al.  An omics-based machine learning approach to predict diabetes progression: a RHAPSODY study Diabetologia SomaScan Butler, AE. et al. A Cross-Sectional Study of Protein Changes Associated with Dementia in Non-Obese Weight Matched Women with and without Polycystic Ovary Syndrome Int J Mol Sci. SomaScan Watson, KT. et al.  Proteomic profiles of cytokines and chemokines in moderate to severe depression: Implications for comorbidities and biomarker discovery Brain, Behavior, & Immunity - Health SomaScan Singh, B. et al.  Enhancing cardiovascular risk prediction through proteomics? Cardiovasc Res. SomaScan Yuan, S. et al.  Proteomic insights into modifiable risk of venous thromboembolism and cardiovascular comorbidities J Thromb Haemost.  SomaScan Duijvelaar, E. et al.  Imatinib treatment improves hyperglycaemic dysregulation in severe COVID-19: a secondary analysis of blood biomarkers in a randomised controlled trial Critical Care SomaScan Wang, JL. et al.  Non-invasive diagnosis of non-alcoholic fatty liver disease: Current status and future perspective Heliyon SomaScan Zhang, L.et. al. Aptamer proteomics for biomarker discovery in heart failure with reduced ejection fraction Circulation SomaScan Austin, TR. et al. Large-scale circulating proteome association study (CPAS) meta-analysis identifies circulating proteins and pathways predicting incident hip fractures JBMR SomaScan Wolf, J. et al. Liquid Biopsy Proteomics in Ophthalmology J. Proteome Res. SomaScan Hedou, J. et al. Discovery of sparse, reliable omic biomarkers with Stabl Nat Biotechnol. SomaScan Kuku, KO. et al. Development and Validation of a Protein Risk Score for Mortality in Heart Failure : A Community Cohort Study Ann Intern Med. SomaScan Kaput, J. et al. Human Nutrition Research in the Data Era: Results of 11 Reports on the Effects of a Multiple-Micronutrient- Intervention Study Nutrients SomaScan Rubenstein, AI. et al. Immune-mediated thrombocytopenia and IL-6-mediated thrombocytosis observed in idiopathic multicentric Castleman disease Br J Haematol. SomaScan Zhu, J. et al. Associations between genetically predicted plasma protein levels and Alzheimer's disease risk: a study using genetic prediction models Alzheimers Res Ther. SomaScan Azzo, JD. et al. Proteomic Associations Of N-terminal-pro Hormone Bnp In Heart Failure With Preserved Ejection Fraction In Two Cohorts J Card Fail. SomaScan Axelsson, GT. et al. Proteomic associations with forced expiratory volume: a Mendelian randomisation study Respir. Res. SomaScan Boehler, JF. et al. N-terminal titin fragment: a non-invasive, pharmacodynamic biomarker for microdystrophin efficacy Skeletal Muscle SomaScan Shah, AM. et al. Large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development Nat. Commun. SomaScan Zhang, W. et al. Therapeutic targets for diabetic kidney disease: proteome-wide Mendelian randomization and colocalization analyses Diabetes SomaScan Ulrich, A. et al. Blood DNA methylation profiling identifies cathepsin Z dysregulation in pulmonary arterial hypertension Nat. Commun. SomaScan Rashid, M. et al. Chloride Intracellular Channel Protein 1 (CLIC1) Is a Critical Host Cellular Factor for Influenza A Virus Replication Viruses SomaScan Rusiñol, L. et al. Multi-Omics Approach to Improved Diagnosis and Treatment of Atopic Dermatitis and Psoriasis Int. J. Mol. Sci. SomaScan Chen, Y. et al. Genetic insights into associations of multisite chronic pain with common diseases and biomarkers using data from the UK Biobank Br J Anaesth. SomaScan Butler, AE. et al. A Cross-Sectional Study of Alzheimer-Related Proteins in Women with Polycystic Ovary Syndrome Int J Mol Sci. SomaScan Cervia-Hasler, C. et al. Persistent complement dysregulation with signs of thromboinflammation in active Long Covid Science SomaScan Curtis, BE. et al. An Aptamer-Based Proteomic Analysis of Plasma from Cats (Felis catus) with Clinical Feline Infectious Peritonitis Viruses SomaScan Smilnak, GJ. et al. Plasma protein signatures of adult asthma Allergy SomaScan Guru Murthy, GS. et al. Proteomics to predict relapse in patients with myelodysplastic neoplasms undergoing allogeneic hematopoietic cell transplantation Biomark Res. SomaScan Akita, K. et al. Prediction of Cardiac Death in Patients with Hypertrophic Cardiomyopathy Using Plasma Adipokine Levels NMCD SomaScan Kuku, KO. et al. Proteomics for heart failure risk stratification: a systematic review BMC Med. SomaScan Gobeil, E. et al. Genetic inhibition of angiopoietin-like protein-3, lipids, and cardiometabolic risk Eur Heart J. SomaScan Link, VM. et al. Differential peripheral immune signatures elicited by vegan versus ketogenic diets in humans Nat Med. SomaScan Duijvelaar, E. et al. Longitudinal plasma proteomics reveals biomarkers of alveolar-capillary barrier disruption in critically ill COVID-19 patients Nat Commun. SomaScan Alkis, T. et al. A polygenic risk score of atrial fibrillation improves prediction of lifetime risk for heart failure ESC Heart Fail. SomaScan Li, H. et al. Proteome-Wide Mendelian Randomization identifies causal plasma proteins in lung cancer iScience SomaScan Choi, B. et al. Proteomic Biomarkers of Quantitative Interstitial Abnormalities in COPDGene and CARDIA Lung Study Am J Respir Crit Care Med. SomaScan Shelbaya, K. et al. Large-Scale Proteomics Identifies Novel Biomarkers and Circulating Risk Factors for Aortic Stenosis J Am Coll Cardiol. SomaScan Azzo, JD. et al. Proteomic Associations of NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) in Heart Failure With Preserved Ejection Fraction Circ Heart Fail. SomaScan Wittich, H. et al. Transcriptome-wide association study of the plasma proteome reveals cis and trans regulatory mechanisms underlying complex traits Am J Hum Genet. SomaScan Zhao, H. et al. Identifying novel proteins for suicide attempt by integrating proteomes from brain and blood with genome-wide association data Neuropsychopharmacology SomaScan Russell, AJ. et al. Modulating fast skeletal muscle contraction protects skeletal muscle in animal models of Duchenne muscular dystrophy J Clin Invest. SomaScan Xiang, X. et al. Mechanistically based blood proteomic markers in the TGF-β pathway stratify risk of hepatocellular cancer in patients with cirrhosis Genes Cancer SomaScan Pase, MP. et al. Association of Plasma YKL-40 With MRI, CSF, and Cognitive Markers of Brain Health and Dementia Neurology SomaScan Carry, P. et al. Untargeted Serum Proteomics Profiling in Female Patients with Idiopathic Scoliosis MRA SomaScan Wenk, D. et al. Recent developments in mass-spectrometry-based targeted proteomics of clinical cancer biomarkers Clin Proteomics SomaScan Fu, L. et al. Serum/Plasma Proteome in Non-Malignant Liver Disease Int. J. Mol. Sci. SomaScan Furuya, K. et al. High serum proteinase-3 levels predict poor progression-free survival and lower efficacy of bevacizumab in metastatic colorectal cancer BMC Cancer SomaScan Yu, G. et al. Lessons and Applications of Omics Research in Diabetes Epidemiology Curr Diab Rep. SomaScan Krishnamoorthy, S. et al. Plasma Proteome-Wide Mendelian Randomization Analysis Reveals Biomarkers and Therapeutic Targets for Different Stages of COVID-19 Transboundary and Emerging Diseases SomaScan Fernández-Irigoyen, J. et al. Special Issue “Deployment of Proteomics Approaches in Biomedical Research” Int. J. Mol. Sci. SomaScan Strecker, L. et al. Proteomic Analysis of Bronchoalveolar Lavage Fluid from Children with Bronchiolitis Obliterans Syndrome Identifies Potential Treatment Strategies Transplantation and Cellular Therapy SomaScan Cartas-Cejudo, P. et al. Mapping the human brain proteome: opportunities, challenges, and clinical potential Expert Rev Proteomics SomaScan Leung, JM. et al. Plasma SOMAmer proteomics of postoperative delirium Brain Behav. SomaScan Kiessling, P. et al. Spatial multi-omics: novel tools to study the complexity of cardiovascular diseases Genome Med. SomaScan Kurgan, N. et al. Harnessing the power of proteomics in precision diabetes medicine Diabetologia SomaScan Gold, ME. et al. Multi-proteomic Biomarker Risk Scores for Predicting Risk and Guiding Therapy in Patients with Coronary Artery Disease Curr Cardiol Rep. SomaScan Evans, DS. et al. Proteomic Analysis of the Senescence Associated Secretory Phenotype (SASP): GDF-15, IGFBP-2, and Cystatin-C Are Associated with Multiple Aging Traits J Gerontol A Biol Sci Med Sci. SomaScan Chen, L. et al. Proteome-wide Mendelian randomization highlights AIF1 and HLA-DQA2 as targets for primary sclerosing cholangitis Hepatol Int. SomaScan Grabowska, I. et al. Multiplex electrochemical aptasensors for detection of endothelial dysfunction: Ready for prime time? TrAC SomaScan Mousa, H. et al. Vitamin D status affects proteomic profile of HDL associated proteins and inflammatory mediators in dyslipidemia J Nutr Biochem. SomaScan Palà, E. et al. Common and specific proteins and pathways in heart and cerebral ischemia J Stroke Cerebrovasc Dis. SomaScan Han, BX. et al. Screening Plasma Proteins for the Putative Drug Targets for Carpal Tunnel Syndrome Cell Mol Neurobiol. SomaScan Mathews, L. et al. Growth Differentiation Factor 15 and Risk of Bleeding Events: The Atherosclerosis Risk in Communities Study J Am Heart Assoc. SomaScan Du, S.et al. Plasma Protein Biomarkers of Healthy Dietary Patterns: Results from the Atherosclerosis Risk in Communities Study and the Framingham Heart Study J Nutr. SomaScan Kiernan, E. et al. Alterations in the Circulating Proteome Associated with Albuminuria J Am Soc Nephrol. SomaScan Steffen, BT. et al. Proteomics Analysis of Genetic Liability of Abdominal Aortic Aneurysm Identifies Plasma Neogenin and Kit Ligand: The ARIC Study Arterioscler Thromb Vasc Biol. SomaScan Chen, M. et al. Growth Differentiation Factor 15 and the Subsequent Risk of Atrial Fibrillation: The Atherosclerosis Risk in Communities Study Clin Chem. SomaScan Grams, ME. et al. Proteins Associated with Risk of Kidney Function Decline in the General Population J Am Soc Nephrol. SomaScan Soomro, S. et al. Predicting disease course in ulcerative colitis using stool proteins identified through an aptamer-based screen Nat Commun. SomaScan Dalby, E. et al. Immune Complex–Driven Generation of Human Macrophages with Anti-Inflammatory and Growth-Promoting Activity J Immunol. SomaScan Shen, Q. et al. Strong impact on plasma protein profiles by precentrifugation delay but not by repeated freeze-thaw cycles, as analyzed using multiplex proximity extension assays Clin Chem Lab Med. SomaScan Considine, DPC. et al. Genetically predicted circulating protein biomarkers and ovarian cancer risk Gynecol Oncol. SomaScan Shchukina, I. et al. Enhanced epigenetic profiling of classical human monocytes reveals a specific signature of healthy aging in the DNA methylome Nat Aging SomaScan Takanashi, S. et al. Lymphadenopathy in IgG4-related disease: a phenotype of severe activity and poor prognosis, with eotaxin-3 as a new biomarker Rheumatology (Oxford) SomaScan Faquih, T. et al. Agreement of aptamer proteomics with standard methods for measuring venous thrombosis biomarkers Res Pract Thromb Haemost. SomaScan Bell, S. et al. A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis Commun Biol SomaScan Moin, ASM. et al. The relationship of soluble neuropilin-1 to severe COVID-19 risk factors in polycystic ovary syndrome Metabol Open. SomaScan Atkin, AS. et al. Plasma heat shock protein response to euglycemia in type 2 diabetes BMJ Open Diabetes Res Care. SomaScan Moin, ASM. et al. Hypoglycaemia in type 2 diabetes exacerbates amyloid‐related proteins associated with dementia Diabetes Obes Metab. SomaScan Pratte, KA. et al. Soluble receptor for advanced glycation end products (sRAGE) as a biomarker of COPD Respir Res. SomaScan Moin, ASM. et al. Amyloid-related protein changes associated with dementia differ according to severity of hypoglycemia BMJ Open Diabetes Res Care. SomaScan Wagner, BD. et al. Change in circulating proteins during treatment of pulmonary exacerbation in patients with cystic fibrosis Health Sci Rep. SomaScan Israël, L. et al. CARD10 cleavage by MALT1 restricts lung carcinoma growth in vivo Oncogenesis SomaScan Vujkovic-Cvijin, I. et al. The complement pathway is activated in people with human immunodeficiency virus and is associated with non-AIDS comorbidities J Infect Dis. SomaScan Luo, S. et al. Platelet glycoprotein Ib α‐chain as a putative therapeutic target for juvenile idiopathic arthritis: A Mendelian randomization study Arthritis Rheumatol. SomaScan Kaeser, SA. et al. A neuronal blood marker is associated with mortality in old age Nat Aging SomaScan Probert, F. et al. Integrative biochemical, proteomics, and metabolomics cerebrospinal fluid biomarkers predict clinical conversion to multiple sclerosis Brain Commun. SomaScan Moin, ASM. et al. Identification of macrophage activation-related biomarkers in obese type 2 diabetes that may be indicative of enhanced respiratory risk in COVID-19 Sci Rep. SomaScan Yakah, W. et al. Parenteral lipid emulsions induce unique ileal fatty acid and metabolomic profiles but do not increase the risk of necrotizing enterocolitis in preterm pigs Am J Physiol Gastrointest Liver Physiol. SomaScan Muñiz-Castrillo, S. et al. Distinctive clinical presentation and pathogenic specificities of anti-AK5 encephalitis Brain SomaScan Mohanty, SK. et al. HMGB1 release by cholangiocytes governs biliary atresia pathogenesis and correlates with increases in afflicted infants Hepatology SomaScan Ngo, D. et al. Proteomic profiling reveals biomarkers and pathways in type 2 diabetes risk JCI Insight SomaScan Jalal, D. et al. Detection of pro angiogenic and inflammatory biomarkers in patients with CKD Sci Rep. SomaScan Emilsson, V. et al. Serum levels of ACE2 are higher in patients with obesity and diabetes Obes Sci Pract. SomaScan Landino, K. et al. Characterization of the plasma proteomic profile of frailty phenotype Geroscience SomaScan Liu, L. et al. Twelve new genomic loci associated with bone mineral density Front Endocrinol. SomaScan Martin, TC. et al. Dysregulated antibody, natural killer cell and immune mediator profiles in autoimmune thyroid diseases Cells SomaScan Simic, P. et al. Glycerol-3-phosphate is an FGF23 regulator derived from the injured kidney J Clin Invest. SomaScan Fong, TG. et al. Identification of plasma proteome signatures associated with ATN framework using SOMAscan Ann Surg. SomaScan Elhadad, MA. et al. Deciphering the plasma proteome of type 2 diabetes Diabetes SomaScan Nakashima-Nakasuga, C. et al. Serum LOX-1 is a novel prognostic biomarker of colorectal cancer Int J Clin Oncol. SomaScan Steitz, AM. et al. Tumor-associated macrophages promote ovarian cancer cell migration by secreting transforming growth factor beta induced (TGFBI) and tenascin C Cell Death Dis SomaScan Oyama, Y. et al. Intense light pretreatment improves hemodynamics, barrier function and inflammation in a murine model of hemorrhagic shock lung. Mil Med. SomaScan Povero, D. et al. Characterization and proteome of circulating extracellular vesicles as potential biomarkers for NASH Hepatol Commun. SomaScan Ibanez, L. et al. Functional genomic analyses uncover APOE-mediated regulation of brain and cerebrospinal fluid beta-amyloid levels in Parkinson disease Acta Neuropathol Commun. SomaScan Tanaka, T. et al. Plasma proteomic signatures predict dementia and cognitive impairment Alzheimers Dement (N Y). SomaScan Grigorieva, J. et al. Application of protein set enrichment analysis to correlation of protein functional sets with mass spectral features and multivariate proteomic tests Clinical Mass Spectrometry SomaScan Wasiak, S. et al. Epigenetic modulation by apabetalone counters cytokine-driven acute phase response in vitro, in mice and in patients with cardiovascular disease Cardiovasc Ther. SomaScan Yamaguchi, Y. et al. Elevated plasma frowth and differentiation factor 15 predicts incident anemia in older adults aged 60 years and older J Gerontol A Biol Sci Med Sci. SomaScan Shu, X. et al. Evaluation of associations between genetically predicted circulating protein biomarkers and breast cancer risk Int J Cancer. SomaScan Zhu, J. et al. Associations between genetically predicted blood protein biomarkers and pancreatic cancer risk Cancer Epidemiol Biomarkers Prev. SomaScan Fahrmann, JF. et al. Plasma-Derived Extracellular Vesicles Convey Protein Signatures That Reflect Pathophysiology in Lung and Pancreatic Adenocarcinomas Cancers (Basel). SomaScan Noordam, R. et al. Proteome-wide assessment of diabetes mellitus in Qatari identifies IGFBP-2 as a risk factor already with early glycaemic disturbances Arch Biochem Biophys. SomaScan Pan, XY. et al. MFGE8, ALB, APOB, APOE, SAA1, A2M, and C3 as novel biomarkers for stress cardiomyopathy Cardiovasc Ther. SomaScan Tini, G. et al. DNA methylation during human adipogenesis and the impact of fructose Genes Nutr SomaScan Xu, J. et al. Integrated lipidomics and proteomics network analysis highlights lipid and immunity pathways associated with Alzheimer’s disease Transl Neurodegener. SomaScan Tweedie, D. et al. Time-dependent cytokine and chemokine changes in mouse cerebral cortex following a mild traumatic brain injury eLife SomaScan Mastey, E. et al. Identifying protein–metabolite networks associated with COPD phenotypes Metabolites SomaScan Cheng, S. et al. An atlas of genetic correlations between psychiatric disorders and human blood plasma proteome Eur Psychiatry. SomaScan Vujkovic-Cvijin, I. et al. HIV-associated gut dysbiosis is independent of sexual practice and correlates with noncommunicable diseases Nat Commun. SomaScan Kasimir-Bauer, s.et al. Definition and independent validation of a proteomic-classifier in ovarian cancer Cancers (Basel). SomaScan Hanly, PJ. et al. Urine biomarkers of renal renin–angiotensin system activity: Exploratory analysis in humans with and without obstructive sleep apnea Physiol Rep. SomaScan Nayor, M. et al. Aptamer-based proteomic platform identifies novel protein predictors of incident heart failure and echocardiographic traits Circ Heart Fail SomaScan Mueller, SK. et al. Significant polyomic and functional upregulation of the PAPP-A/IGFBP-4/5/IGF-1 axis in chronic rhinosinusitis with nasal polyps Int Forum Allergy Rhinol. SomaScan Workman, AD. et al. Unexpected effects of systemic steroids on the CRSwNP proteome: Is protein upregulation more important than inhibition? Int Forum Allergy Rhinol. SomaScan Sasayama, D. et al. Increased apolipoprotein E and decreased TNF‐α in the cerebrospinal fluid of nondemented APOE‐ε4 carriers Neuropsychopharmacol Rep SomaScan Schaum, N. et al. Aging hallmarks exhibit organ-specific temporal signatures Nature SomaScan Hunt, ER. et al. Upregulation of systemic inflammatory pathways following anterior cruciate ligament injury relates to both cartilage and muscular changes: A pilot study J Orthop Res. SomaScan Toyoda, E. et al. Transcriptomic and proteomic analyses reveal the potential mode of action of chondrocyte sheets in hyaline cartilage regeneration Int J Mol Sci SomaScan Egerstedt, A. et al. Profiling of the plasma proteome across different stages of human heart failure Nat Commun. SomaScan Wang, Z. et al. Airway host-microbiome interactions in chronic obstructive pulmonary disease Respir Res. SomaScan Pavlidis, S. et al. “T2-high” in severe asthma related to blood eosinophil, exhaled nitric oxide and serum periostin Eur Respir J. SomaScan Polfus, LM. et al. Whole genome sequence association with E-selectin levels reveals loss-of-function variant in African Americans Hum Mol Genet SomaScan Doulamis, IP. et al. Transcriptomic and proteomic pathways of diabetic and non-diabetic mitochondrial transplantation Sci Rep. SomaScan Tsypin, M. et al. Extending the information content of the MALDI analysis of biological fluids via multi-million shot analysis PLoS ONE SomaScan Jevnikar, Z. et al. Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation J Allergy Clin Immunol. SomaScan Laksitorini, MD. et al. Modulation of Wnt/β-catenin signaling promotes blood-brain barrier phenotype in cultured brain endothelial cells Sci Rep. SomaScan Harbaum, L. et al. Reduced plasma levels of small HDL particles transporting fibrinolytic proteins in pulmonary arterial hypertension Thorax SomaScan MacDonald, A. et al. Necuparanib, a multitargeting heparan sulfate mimetic, targets tumor and stromal compartments in pancreatic cancer Mol Cancer Ther. SomaScan Katzen, J. et al. An SFTPC BRICHOS mutant links epithelial ER stress and spontaneous lung fibrosis JCI Insight SomaScan Bradford, CM. et al. Characterization of a subset of patients with rheumatoid arthritis for whom current management strategies are inadequate ACR Open Rheumatol SomaScan Mancuso, R. et al. CSF1R inhibitor JNJ- attenuates microglial proliferation and neurodegeneration in P301S mice Brain SomaScan Joyce, R. et al. TGF-β signaling underlies hematopoietic dysfunction and bone marrow failure in Shwachman-Diamond syndrome J Clin Invest. SomaScan Todd, JL. et al. Peripheral blood proteomic profiling of idiopathic pulmonary fibrosis biomarkers in the multicentre IPF-PRO registry Respir Res. SomaScan Keulen, DV. et al. Oncostatin M reduces atherosclerosis development in APOE*3Leiden.CETP mice and is associated with increased survival probability in humans PLoS ONE SomaScan Higgins, SJ. et al. Tie2 protects the vasculature against thrombus formation in systemic inflammation J Clin Invest. SomaScan Billin, AN. et al HIF prolyl hydroxylase inhibition protects skeletal muscle from eccentric contraction-induced injury Skelet Muscle SomaScan Hoffman, LK. et al. Integrating the skin and blood transcriptomes and serum proteome in hidradenitis suppurativa reveals complement dysregulation and a plasma cell signature PLoS ONE SomaScan Gopal, AK. et al. Ibrutinib as treatment for patients with relapsed/refractory follicular Lymphoma: Results from the open-label, multicenter, phase II DAWN study J Clin Oncol. SomaScan Takahashi, K. et al. Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis Eur Respir J. SomaScan Malik, R. et al. Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes Nat Genet. SomaScan Wu, D. et al. Axonal guidance signaling pathway is suppressed in human nasal polyps Am J Rhinol Allergy. SomaScan Wu, D. et al. TREM-1 neutrophil activation pathway is suppressed in eosinophilic nasal polyps Am J Rhinol Allergy. SomaScan Kuo, CS. et al. T-helper cell type 2 (Th2) and non-Th2 molecular phenotypes of asthma using sputum transcriptomics in U-BIOPRED Eur Respir J. SomaScan Shah, RD. et al. Expression of calgranulin genes S100A8, S100A9 and S100A12 is modulated by n-3 PUFA during inflammation in adipose tissue and mononuclear cells PLoS ONE SomaScan Lim, SY. et al. Evaluation of two high-throughput proteomic technologies for plasma biomarker discovery in immunotherapy-treated melanoma patients Biomark Res. SomaScan Sullivan, KD. et al. Trisomy 21 consistently activates the interferon response eLife SomaScan Loza, MJ. et al. Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study Respir Res. SomaScan Bar-Or, D. et al. Low molecular weight fraction of commercial human serum albumin induces morphologic and transcriptional changes of bone marrow-derived mesenchymal stem cells Stem Cells Transl Med. SomaScan Natrajan, MS. et al. Pioglitazone regulates myelin phagocytosis and multiple sclerosis monocytes Ann Clin Transl Neurol. SomaScan Silkoff, PE. et al. Asthma characteristics and biomarkers from the airways disease endotyping for personalized therapeutics (ADEPT) longitudinal profiling study Respir Res. SomaScan Coenen-Stass, AM. et al. Identification of novel, therapy-responsive protein biomarkers in a mouse model of Duchenne muscular dystrophy by aptamer-based serum proteomics Sci Rep. SomaScan Chiam, JT. et al. No Evidence to Suggest that the Use of Acetylcholinesterase Inhibitors Confounds the Results of Two Blood-Based Biomarker Studies in Alzheimer's Disease J Alzheimers Dis. SomaScan Loza, M. et al. Systemic corticosteroid-associated serum analyte profiles in the U-BIOPRED severe asthma cohort Eur Respir J. SomaScan Christiansson, L. et al. The use of multiplex platforms for absolute and relative protein quantification of clinical material EuPA Open Proteomics SomaScan Thorolfsdottir, RB. et al. Variants at the Interleukin 1 Gene Locus and Pericarditis JAMA Cardiol. SomaScan Abiose, O. et al. Post-translational modifications linked to preclinical Alzheimer's disease-related pathological and cognitive changes Alzheimers Dement. SomaScan Jordan, HA. et al. Novel proteomic technologies to address gaps in pre-clinical ovarian cancer biomarker discovery efforts Expert Rev Proteomics SomaScan Emilsson, V. et al. Proteomic prediction of incident heart failure and its main subtypes Eur J Heart Fail SomaScan Serio, B. et al. All Roads Lead to Interferon-γ: From Known to Untraveled Pathways in Acquired Aplastic Anemia Medicina SomaScan Asamoah, K. et al. Proteomic signatures of eosinophilic and neutrophilic asthma from serum and sputum EBioMedicine SomaScan Chen, TK. et al. Associations of Baseline and Longitudinal Serum Uromodulin With Kidney Failure and Mortality: Results From the African American Study of Kidney Disease and Hypertension (AASK) Trial Am J Kidney Dis SomaScan Gold, ME. et al. Multi-proteomic Biomarker Risk Scores for Predicting Risk and Guiding Therapy in Patients with Coronary Artery Disease Curr Cardiol Rep SomaScan Papagiannopoulos, OD. et al. Classification of Inflammation of Unknown Origin patients based on RNA-seq and SomaScan data Annu Int Conf SomaScan Wen, Y. et al. Analysis of the human kidney transcriptome and plasma proteome identifies markers of proximal tubule maladaptation to injury Sci Transl Med. SomaScan Cardner, M. et al. Analysis of serum proteomics data identifies a quantitative association between beta-defensin 2 at baseline and clinical response to IL-17 blockade in psoriatic arthritis RMD Open SomaScan Graham, BIM. Integrating airway microbiome and blood proteomics data to identify multi-omic networks associated with response to pulmonary infection The Microbe SomaScan Brennan, E. et al. Relationship between endocrine disrupting chemicals (phthalate metabolites, triclosan and bisphenols) and vitamin D in female subjects: An exploratory pilot study Chemosphere SomaScan Bonaroti, JW. et al. Transcriptomic and Proteomic Characterization of the Immune Response to Elective Spinal Reconstructive Surgery: Impact of Aging and Comparisons with the Traumatic Injury Response J Am Coll Surg. SomaScan Ren, Y. et al. Evaluation of a large-scale aptamer proteomics platform among patients with kidney failure on dialysis PLoS One SomaScan Fullenkamp, DE. et al. Physiological stress improves stem cell modeling of dystrophic cardiomyopathy Dis Model Mech. SomaScan Oh, HS. et al. Organ aging signatures in the plasma proteome track health and disease Nature SomaScan Li, J. et al. Circulating Biomarkers and Risk of Hypertension: A Two-Sample Mendelian Randomisation Study Heart Lung Circ. SomaScan Yang, F. et al. Proteomic insights into the associations between obesity, lifestyle factors, and coronary artery disease BMC Med. SomaScan Thomson, LM. et al. The proteomic fingerprint in infants with single ventricle heart disease in the interstage period: evidence of chronic inflammation and widespread activation of biological networks Front. Pediatr SomaScan Akenroye, A. et al. Lower myostatin and higher MUC1 levels are associated with better response to mepolizumab and omalizumab in asthma: a protein-protein interaction analyses Respir Res SomaScan Farid, S. et al. Aptamer-Based Optical and Electrochemical Sensors: A Review Chemosensors SomaScan Goudswaard, LJ. et al. Using trials of caloric restriction and bariatric surgery to explore the effects of body mass index on the circulating proteome Sci Rep SomaScan 11/29/ Mälarstig, A. et al. Evaluation of circulating plasma proteins in breast cancer using Mendelian randomisation Nat Commun SomaScan 11/24/ Jonmundsson, T. et al. A proteomic analysis of atrial fibrillation in a prospective longitudinal cohort (AGES-Reykjavik study) Europace SomaScan 11/15/ Adams, JM. et al. Leukotriene A4 hydrolase inhibition improves agerelated cognitive decline via modulation of synaptic function Sci Adv. SomaScan 11/15/ Castro-Pearson, S. et al. Development of a proteomic signature associated with severe disease for patients with COVID-19 using data from 5 multicenter, randomized, controlled, and prospective studies Sci Rep. SomaScan 11/20/ McMackin, R. et al. Biomarkers in amyotrophic lateral sclerosis: current status and future prospects Nat Rev Neurol SomaScan Wickramasinghe, LC. et al. Granulocyte colony-stimulating factor is a determinant of severe bronchopulmonary dysplasia and coincident retinopathy Am J Pathol SomaScan 09/04/ Vaquer-Alicea, A. et al. Plasma and CSF Proteomic Signatures of Acutely Sleep-Deprived Humans: An Exploratory Study SLEEP Advances SomaScan Stacey, SN. et al. Genetics and epidemiology of mutational barcode-defined clonal hematopoiesis Nat Genet SomaScan 11/06/ Dörner, T. et al. Efficacy and safety of remibrutinib, a selective potent oral BTK inhibitor, in Sjögren's syndrome: results from a randomised, double-blind, placebo-controlled phase 2 trial Ann Rheum Dis. SomaScan 11/06/ Pan, M. et al. Genetic Predisposition to Elevated Levels of Circulating ADAM17 Is Associated with the Risk of Severe COVID-19 Int. J. Mol. Sci. SomaScan Niazi, S. et al. A Critical Analysis of the FDA’s Omics-Driven Pharmacodynamic Biomarkers to Establish Biosimilarity Pharmaceuticals SomaScan Woo, J. et al. Effects of IL-1β inhibition on anemia and clonal hematopoiesis in the randomized CANTOS trial Blood Adv. SomaScan 11/07/ Dowling, P. et al. Mass Spectrometry-Based Proteomic Technology and Its Application to Study Skeletal Muscle Cell Biology Cells SomaScan Sun, J. et al. Unveiling the Association between HPV and Pan Cancers: A Bidirectional Two-Sample Mendelian Randomization Study Cancers SomaScan Bjornsdottir, G, et al. Rare variants with large effects provide functional insights into the pathology of migraine subtypes, with and without aura Nat Genet SomaScan 10/26/ Tin, A. et al. Identification of circulating proteins associated with general cognitive function among middle-aged and older adults Commun Biol. SomaScan 11/03/ Carrasco-Zanini, J. et al. Multi-omic prediction of incident type 2 diabetes Diabetologia SomaScan 10/27/ Gîlcă-Blanariu, GE. et al. Advances in Noninvasive Biomarkers for Nonalcoholic Fatty Liver Disease Metabolites SomaScan Jackson, HR. et al. A multi-platform approach to identify a blood-based host protein signature for distinguishing between bacterial and viral infections in febrile children (PERFORM): a multi-cohort machine learning study Lancet Digit Health SomaScan Gorijala, P. et al. Alzheimer's polygenic risk scores are associated with cognitive phenotypes in Down syndrome Alzheimers Dement. SomaScan 10/19/ Aid, M. et al. Activation of coagulation and proinflammatory pathways in thrombosis with thrombocytopenia syndrome and following COVID-19 vaccination Nat Commun. SomaScan 10/23/ Yellin, B. et al. Analytical validation of the PROphet test for treatment decision-making guidance in metastatic non-small cell lung cancer J Pharm Biomed Anal. SomaScan 10/19/ Lee, D. et al. Decentralized clinical trial design using blood microsampling technology for serum bioanalysis Bioanalysis SomaScan 10/19/ Cordon, J. et al. Identification of Clinically Relevant Brain Endothelial Cell Biomarkers in Plasma Stroke SomaScan Jin, L. et al. Identification of Plasma Biomarkers from Rheumatoid Arthritis Patients Using an Optimized Sequential Window Acquisition of All THeoretical Mass Spectra (SWATH) Proteomics Workflow Proteomes SomaScan Gao, J. et al. The application of multi-omics in the respiratory microbiome: Progresses, challenges and promises Comput Struct Biotechnol J SomaScan 10/12/ Sigdel, TK. et al. Proteome Analysis for Inflammation Related to Acute and Convalescent Infection Inflammation SomaScan 10/13/ Aid, M. et al. Mpox infection protects against re-challenge in rhesus macaques Cell SomaScan 10/12/ Wolf, J. et al. Liquid-biopsy proteomics combined with AI identifies cellular drivers of eye aging and disease in vivo Cell SomaScan 10/26/ Dubin, RF. et al. Proteomics of CKD progression in the chronic renal insufficiency cohort Nat Commun. SomaScan 10/10/ Bohn, T. et al. Carotenoids in health as studied by omics-related endpoints Adv Nutr. SomaScan 09/05/ Butler, AE. et al. SAT366 Expression of Amyloid-related Proteins Associated With Dementia in Polycystic Ovary Syndrome Compared to a Control Population Journal of the Endocrine Society SomaScan de Bakker, M. et al. Machine learning based biomarker profile derived from serially measured proteins predicts clinical outcome of patients with heart failure European Heart Journal - Digital Health SomaScan Krauze, AV. et al. Revisiting Concurrent Radiation Therapy, Temozolomide, and the Histone Deacetylase Inhibitor Valproic Acid for Patients with Glioblastoma—Proteomic Alteration and Comparison Analysis with the Standard-of-Care Chemoirradiation Biomolecules SomaScan Larsson, SC. et al. Genome-Wide Association and Two-Sample Mendelian Randomization Analyses of Plasma Ghrelin and Gastrointestinal Cancer Risk Cancer Epidemiol Biomarkers SomaScan 10/04/ Dark HE. et al. Proteomic indicators of health predict Alzheimer's disease biomarker levels and dementia risk Ann Neurol. SomaScan 10/06/ Singh, VK. et al. Proteome biomarkers for radiation injury and testing of medical countermeasure efficacy: promises, pitfalls and future directions Expert Rev Proteomics SomaScan 09/26/ Di Mauro, V. et al. Diagnostic and Therapeutic Aptamers: A Promising Pathway to Improved Cardiovascular Disease Management JACC: Basic to Translational Science SomaScan Markezana, A. et al. Fibroblast growth factors induce hepatic tumorigenesis post radiofrequency ablation Sci Rep. SomaScan 09/28/ Wang, Q. et al. Integrating plasma proteomes with genome-wide association data for causal protein identification in multiple myeloma BMC Med. SomaScan 09/29/ Eldjarn, GH. Et al. Large-scale plasma proteomics comparisons through genetics and disease associations Nature SomaScan 10/04/ Perry , AS. Et al. Proteomic architecture of frailty across the spectrum of cardiovascular disease Aging Cell SomaScan 09/20/ Dillon, ST. et al. Aptamer-Based Proteomics Measuring Preoperative Cerebrospinal Fluid Protein Alterations Associated with Postoperative Delirium Biomolecules SomaScan 09/15/ Mousavian Z. et al. From simple to complex: protein-based biomarker discovery in tuberculosis Eur J Immunol. SomaScan 09/23/ Frank, B. et al. Circulating biomarkers of extracellular matrix dysregulation are associated with adverse post-stage 2 outcomes in infants with single ventricle heart disease Sci Rep SomaScan 09/28/ Visvabharathy, L. et al. Neuro-PASC is characterized by enhanced CD4+ and diminished CD8+ T cell responses to SARS-CoV-2 Nucleocapsid protein Front Immunol SomaScan 05/29/ Chan, WC. et al. Fibroscan-AST (FAST) score and other non-invasive tests for the diagnosis of fibrotic non-alcoholic steatohepatitis HepatoBiliary Surg Nutr SomaScan Babačić, H. et al. Comprehensive proteomics and meta-analysis of COVID-19 host response Nat Commun. SomaScan 09/22/ Sattar, N. et al. Prediction of Cardiometabolic Health Through Changes in Plasma Proteins With Intentional Weight Loss in the DiRECT and DIADEM-I Randomized Clinical Trials of Type 2 Diabetes Remission Diabetes Care SomaScan 09/26/ D'Erasmo, L. et al. ANGPTL3 Deficiency and Risk of Hepatic Steatosis Circulation SomaScan Dowling, P. et al. Biochemical and proteomic insights into sarcoplasmic reticulum Ca2+-ATPase complexes in skeletal muscles Expert Rev Proteomics. SomaScan Hanson, BA. et al. Plasma proteomics show altered inflammatory and mitochondrial proteins in patients with neurologic symptoms of post-acute sequelae of SARS-CoV-2 infection Brain Behav Immun. SomaScan Hota, M. et al. Omics-driven investigation of the biology underlying intrinsic submaximal working capacity and its trainability Physiol Genomics. SomaScan Ngo, D. et al. Systemic Markers of Lung Function and FEV1 Decline across Diverse Cohorts Ann Am Thorac Soc. SomaScan 06/23/ Reitz, CJ. et al. Multi-omic analyses and network biology in cardiovascular disease Proteomics. SomaScan 09/10/ Weiner, S. et al. Next-generation proteomics technologies in Alzheimer's disease: from clinical research to routine diagnostics Expert Rev Proteomics SomaScan 09/13/ Liu, F. et al. Late-life plasma proteins associated with prevalent and incident frailty: A proteomic analysis Aging Cell SomaScan 09/11/ Zhong, H. et al. Identification of blood protein biomarkers associated with prostate cancer risk using genetic prediction models: analysis of over 140 000 subjects Hum Mol Genet. SomaScan 08/25/ Johansson, MW. et al. Decreased plasma cartilage acidic protein 1 in COVID-19 Physiol Rep. SomaScan 09/11/ Yao, P. et al. Conventional and genetic associations of adiposity with proteins in relatively lean Chinese adults Eur J Epidemiol. SomaScan 09/07/ Srialluri, N. et al. Circulating Proteins and Mortality in CKD: A Proteomics Study of the AASK and ARIC Cohorts Kidney Medicine SomaScan 10/01/ Doherty, C. et al. Aptamers in neuro-oncology: an emerging therapeutic modality Neuro Oncol. SomaScan 08/24/ Cai, X. et al. Population serum proteomics uncovers a prognostic protein classifier for metabolic syndrome Cell Rep Med. SomaScan 08/20/ Yuan, S. et al. Plasma proteins and onset of type 2 diabetes and diabetic complications: Proteome-wide Mendelian randomization and colocalization analyses Cell Rep Med. SomaScan 08/22/ Muse, O. et al. The unfolded protein response links ER stress to cancer-associated thrombosis JCI Insight. SomaScan 08/31/ Mahoney, SA. et al. Identification and functional analysis of senescent cells in the cardiovascular system using omics approaches Am J Physiol Heart Circ Physiol. SomaScan 09/01/ Rhee, J. et al. Cardioprotective and Anti-Inflammatory Effects of FAM3D in Myocardial Ischemia-Reperfusion Injury Circulation Research SomaScan 08/28/ Helgason H. et al. Evaluation of Large-Scale Proteomics for Prediction of Cardiovascular Events JAMA SomaScan 08/22/ Krauze, AV. et al. Glioblastoma survival is associated with distinct proteomic alteration signatures post chemoirradiation in a large-scale proteomic panel Front Oncol. SomaScan 08/10/ Yaghoobi, A. et al. Genome- and Exome-Wide Association Studies Revealed Candidate Genes Associated with DaTscan Imaging Features Parkinson’s Disease SomaScan Goldberg, JF. et al. Selection and Interpretation of Molecular Diagnostics in Heart Transplantation Circulation SomaScan 08/22/ Wang, H. et al. Subgroups of children with Kawasaki disease: a data-driven cluster analysis Lancet Child Adolesc Health. SomaScan 08/17/ Magnusson, M. et al. Histopathology and levels of proteins in plasma associate with survival after colorectal cancer diagnosis Br J Cancer. SomaScan 08/18/ Quintana-Torres, D. et al. The secretome atlas of two mouse models of progeria Aging Cell SomaScan 08/10/ Wang, X. et al. Proteome-Wide Mendelian Randomization Analysis Identified Potential Drug Targets for Atrial Fibrillation J Am Heart Assoc. SomaScan 08/15/ Morris, BJ. et al. Genes That Extend Lifespan May Do So by Mitigating the Increased Risk of Death Posed by Having Hypertension Am J Hypertens. SomaScan 08/10/ Benson, MD. et al. Protein-metabolite association studies identify novel proteomic determinants of metabolite levels in human plasma Cell Metab. SomaScan 08/11/ Tsukita, K. et al. High-Throughput CSF Proteomics and Machine Learning to Identify Proteomic Signatures for Parkinson Disease Development and Progression Neurology SomaScan 08/16/ Parnetti, L. et al. Advances in Diagnosis and Prognosis of Parkinson Disease: Value of Cerebrospinal Fluid Proteomics Neurology SomaScan 08/16/ Butler, AE. et al. Complement Dysregulation in Obese Versus Nonobese Polycystic Ovary Syndrome Patients Cells SomaScan 08/04/ Li, H. et al. Proteome-wide mendelian randomization identifies causal plasma proteins in venous thromboembolism development J Hum Genet. SomaScan 08/03/ Geretz, A. et al. plasma proteins in venous thromboembolism development Sci Transl Med. SomaScan 08/02/ Cederberg, KL. et al. Single-cell transcriptomics identifies prothymosin α restriction of HIV-1 in vivo Sleep Health SomaScan 08/08/ Cai, Y. et al. Proteomic insights into the pathophysiology of periodic limb Clin J Am Soc Nephrol. SomaScan 08/03/ Muhie, S. et al. Integrated analysis of proteomics, epigenomics and metabolomics data revealed divergent pathway activation patterns in the recent versus chronic post-traumatic stress disorder Brain Behav Immun. SomaScan 07/27/ Lovell, JP. et al. Serum Proteomic Analysis of Peripartum Cardiomyopathy Reveals Distinctive Dysregulation of Inflammatory and Cholesterol Metabolism Pathways JACC Heart Fail. SomaScan 07/18/ Galbraith, MD. et al. Multidimensional definition of the interferonopathy of Down syndrome and its response to JAK inhibition Sci Adv. SomaScan 06/28/ De Belen, E. et al. Clinical Variation in the Treatment Practices for Patients With Type2 Diabetes: A Cross-Sectional Patient Simulation Study Among Primary Care Physicians and Cardiologists J Am Heart Assoc. SomaScan 06/29/ Kong, AHY. et al. Exploring the Potential of Aptamers in Targeting Neuroinflammation and Neurodegenerative Disorders: Opportunities and Challenges Int. J. Mol. Sci. SomaScan 07/24/ Nandakumar, M. et al. Oxidative Stress Markers and Heat Shock Proteins in Non-Obese Women with Polycystic Ovary Syndrome Are Not Elevated and Show No Correlation with Vitamin D Biomedicines SomaScan 07/11/ Gupta, S. et al. Plasma proteome of growing tumors Sci Rep. SomaScan 07/27/ Walker, KA. et al. Proteomics analysis of plasma from middle-aged adults identifies protein markers of dementia risk in later life Sci Transl Med. SomaScan 07/19/ Li, Y. et al. The application of Aptamer in biomarker discovery Biomarkers Research SomaScan 07/19/ Mi, MY. et al. Plasma Proteomic Kinetics in Response to Acute Exercise Mol Cell Proteomics SomaScan 06/19/ Gregga, I. et al. Predicted proteome association studies of breast, prostate, ovarian, and endometrial cancers implicate plasma protein regulation in cancer susceptibility Cancer Epidemiol Biomarkers Prev. SomaScan 07/06/ Butler, AE. et al. Association of flame retardants, polybrominated diethyl ethers (PBDEs), with vitamin D in female subjects Chemosphere SomaScan 07/11/ Richards, SM. et al. Non-invasive candidate protein signature predicts hepatic venous pressure gradient reduction in cirrhotic patients after sustained virologic response Liver Int. SomaScan 07/13/ Lin, JS. et al. Proteomic profiling of longitudinal changes in kidney function among middle-aged and older men and women: the KORA S4/F4/FF4 study BMC Med. SomaScan 07/05/ Phillips, B. et al. Proteome wide association studies of LRRK2 variants identify novel causal and druggable proteins for Parkinson's disease NPJ Parkinsons Dis. SomaScan 07/08/ Kokelj, S. et al. Activation of the Complement and Coagulation Systems in the Small Airways in Asthma Respiration. SomaScan 07/07/ Roberts, JA. et al. Unbiased proteomics and multivariable regularized regression techniques identify SMOC1, NOG, APCS, and NTN1 in an Alzheimers disease brain proteomic signature NPJ Aging. SomaScan 07/06/ Peabody, JW. et al. Clinical utility of a novel test for assessing cardiovascular disease risk in type 2 diabetes: a randomized controlled trial Diabetol Metab Syndr. SomaScan 07/13/ Beals, JW. et al. Dietary weight loss-induced improvements in metabolic function are enhanced by exercise in people with obesity and prediabetes Nat Metab. SomaScan 06/26/ Cai, L. et al. Causal associations between cardiorespiratory fitness and type 2 diabetes Nat Commun. SomaScan 07/03/ Sung, YJ. et al. Proteomics of brain, CSF, and plasma identifies molecular signatures for distinguishing sporadic and genetic Alzheimer's disease Sci Transl Med. SomaScan 07/05/ Kim, H. et al. Associations of circulating proteins with lipoprotein profiles: proteomic analyses from the OmniHeart randomized trial and the Atherosclerosis Risk in Communities (ARIC) Study Clin Proteomics. SomaScan 07/03/ Lazar, J. et al. Large scale plasma proteome epitome profiling is an efficient tool for the discovery of cancer biomarkers Mol Cell Proteomics SomaScan 05/19/ Liu, T. et al. External validation of genetically predicted protein biomarkers for pancreatic cancer risk using aptamer-based plasma levels: A prospective analysis in the Atherosclerosis Risk in Communities Study Int J Cancer SomaScan 06/20/ Milman, S. et al. Frailty Resilience Score: A Novel Measure of Frailty Resilience Associated with Protection from Frailty and Survival J Gerontol A Biol Sci Med Sci. SomaScan 05/29/ Nash, A. et al. New Markers for Management of Mesothelioma Semin Respir Crit Care Med. SomaScan 05/30/ Bader, JM. et al. MS-based proteomics of body fluids: The end of the beginning Mol Cell Proteomics SomaScan 05/18/ Chen, R. et al. Biomarkers of ageing: Current state-of-art, challenges, and opportunities MedComm – Future Medicine SomaScan 06/18/ Quian, L. et al. Mass Spectrometry-based Proteomics of Epithelial Ovarian Cancers: a Clinical Perspective Mol Cell Proteomics SomaScan 05/18/ Felipez, N. et al. The Human Gastric Juice: A Promising Source for Gastric Cancer Biomarkers Int J Mol Sci. SomaScan Tomasoni, C. et al. A Question of Frame: The Role of the Bone Marrow Stromal Niche in Myeloid Malignancies Hemasphere SomaScan 05/23/ Liang, X. et al. Proteomics approaches to long COVID: status and outlooks Life Medicine SomaScan Lee J. et al. Machine learning algorithm improves detection of NASH (NAS-based) and at-risk NASH, a development and validation study Hepatology SomaScan Ozsoylu, D. et al. (Bio-)Sensors for Skin Grafts and Skin Flaps Monitoring Sensors and Actuators Report SomaScan Brennan, E. et al. Association between Organochlorine Pesticides and Vitamin D in Female Subjects Biomedicines SomaScan 05/15/ DiLillo, K. et al. A blood and bronchoalveolar lavage protein signature of rapid FEV1 decline in smoking-associated COPD Sci Rep. SomaScan 05/22/ Jiang, MZ. et al. Canonical correlation analysis for multi-omics: Application to cross-cohort analysis PLoS Genet. SomaScan 05/22/ de Bakker, M. et al. Sex-based differences in cardiovascular proteomic profiles and their associations with adverse outcomes in patients with chronic heart failure Biol Sex Differ. SomaScan 05/17/ Mackay, S. Identification of serum biomarkers for necrotizing enterocolitis using aptamer-based proteomics Front Pediatr. SomaScan 05/31/ Petersen, TB. et al. HFrEF subphenotypes based on repeatedly measured circulating proteins are driven by different biological mechanisms EBioMedicine SomaScan 06/14/ Iglesias, MJ. et al. Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism Nat Commun SomaScan 06/07/ Giontella, A. et al. Renoprotective effects of genetically proxied fibroblast growth factor 21: Mendelian randomization, proteome-wide and metabolome-wide association study Metabolism SomaScan 06/09/ Gisladottir, R. et al. Sequence variants affecting voice pitch in humans Sci Adv. SomaScan Oddsson, A. et al. Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality Nat Commun. SomaScan 06/10/ DeBoer, E. et al. Cardiopulmonary Phenotypes and Protein Signatures in Children With Down Syndrome Clinical Pediatr. (Phila). SomaScan 06/12/ Lu, S. et al. Magnetically Detected Protein Binding Using Spin-Labeled Slow Off-Rate Modified Aptamers ACS Sens. SomaScan 06/10/ Hill, AC. et al. Large scale proteomic studies create novel privacy considerations Sci Rep. The authors of this paper sought to demonstrate the need for similar privacy protections in proteomic research as genomic research already has. Since the discovery that single nucleotide polymorphisms (SNPs) can genetically distinguish individuals, multiple privacy protection policies regarding genetic information have been passed in the United States. Notably, these policies only explicitly address genetic information, leaving proteomics in a grey area and legally unprotected. The authors use limited proteome profiles without peptide sequencing to link specific individuals by using prior independent knowledge of QTLs The authors used the COPDGene and Jackson Heart studies to train a model to predict genotypes based on SomaScan proteomic measurements. The model was validated using the MESA, SPIROMICS, and splits from the COPDGene and Jackson Heart studies. The model identified independent subjects of European ancestry with 83-92% accuracy and African American subjects with ~90% accuracy. The authors determined that the minimum number of protein-pQTL pairs necessary to match a proteome to a genome is 100 pairs. The authors assessed whether newer and larger proteome assays were more or less accurate at identifying genetic profiles. To do so, they split the COPDGene subjects who had 5k data into a 50/50 train-test split and generated a new list of protein-QTL pairs. These protein-QTL pairs were also used to match proteomes and genomes of participants in the ARIC study who have 5k SomaScan data. Identification accuracy improved to_>_98% in COPDGene and ARIC participants. This study is the first to demonstrate on a large scale that proteomic data are not identity protected because an individual proteome can be matched to a specific genome with high accuracy even without protein sequence information. SomaScan 06/07/ Sasamoto, S. et al. Plasma proteomic profiles of pain subtypes in adolescentsand young adults with endometriosis Hum Reprod SomaScan 05/17/ Debbs, J. et al. Evaluation of a New Aptamer-Based Array for Soluble Suppressor of Tumorgenicity (ST2) and N-terminal Pro-B-Type Natriuretic Peptide (NTproBNP) in Heart Failure Patients J Cardiovasc Transl Res. In this study, SomaScan and ELISA assays were used to measure NTproBNP and ST2 and the results and predictive performance of the two methods were compared. N-terminal pro-B-type natriuretic peptide (NTproBNP) and soluble suppressor of tumorgenicity 2 (ST2) are the two most widely used and recommended biomarkers used for the diagnosis and prognosis of heart failure. The SomaScan assay allows for the rapid detection of thousands of proteins simultaneously, including NTproBNP and ST2. Here, the authors wished to test the accuracy of the SomaScan method for detecting NTproBNP and ST2 by comparing the performance to commercial ELISA assays. EDTA plasma samples from participants from the Henry Ford Pharmacogenomic Registry who met Framingham criterion for HF and had an ejection fraction 0.70) correlations with Olink measurements. Protein associations with longitudinal glucose levels largely reflected those observed in the incident diabetes analyses. In the base model, 59 additional associations were statistically significant. Prospective protein associations were identified in a complementary analysis of multiple glucose homeostasis traits using intravenous glucose tolerance test (IVGTT). 52 significantly associated proteins from the main model were selected and their associations with the following four IVGTT traits in HERITAGE were tested: insulin sensitivity index, acute insulin response to glucose, disposition index, and glucose effectiveness. Insulin sensitivity index, acute insulin response to glucose, disposition index, and glucose effectiveness were respectively associated with 39, 9, 39, and 8 proteins. 90% of significantly associated proteins were associated with at least one IVGTT trait. The study overall observed three patterns of association: 1. Proteins reflecting higher insulin sensitivity were also markers of decreased diabetes risk and vice versa; 2. Proteins relating to pancreatic function had associations with diabetes and insulin secretion but not insulin sensitivity; 3. In the insulin-independent glucometabolic pathways, b-Glucuronidase (GUSB) was most strongly associated with incident diabetes. It is hypothesized that before the onset of overt diabetes, GUSB may be upregulated to compensate for hyperglycemia as the body becomes more insulin resistant. SomaScan 05/01/ Hou, R. et al. The role of inflammation in anxiety and depression in the European U-BIOPRED asthma cohorts Brain Behav Immun. In this study, the authors use data and samples from the largest European asthma cohort, the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) study, and utilize the largest proteomic assay on the market, SomaScan, to address the underlying mechanism between inflammation, asthma, anxiety, and depression. Studies have shown that people with asthma are more likely to experience anxiety, psychological distress, and depression which can lead to poor disease management and lower quality of life. Evidence suggests that inflammation is the link between asthma, anxiety, and depression; however, studies have been limited by small sample sizes, poor study design, and a limited number of available inflammatory markers. Here, behavioral data and serum samples from 198 non-smoking patients with severe asthma (SAn), 65 smoking patients with severe asthma (SAs), 61 non-smoking patients with mild-to-moderate asthma (MMA), and 20 healthy nonsmokers (HC) from the U-BIOPRED were analyzed. Average Hospital Anxiety and Depression Scale (HADS) scores for anxiety, depression, and HADS total scores from this cohort revealed a significantly higher levels in the SAn and SAs groups compared to the MMA and HC groups. Proteomic analysis of inflammatory markers revealed significantly higher levels of IL6, CCL18, MCP1, CCL17, and IL8 in the SAn and SAs groups. When looking at correlations between HADS scores and inflammatory markers, significant positive correlations were found between the depression score and IL6, MCP1, CCL18, and CCL17, the anxiety score and CCL17, and the total score and IL6, CCL18, and CCL17. Correlations between inflammatory markers for air flow obstruction and HADS scores were also analyzed, revealing a small negative correlation between eosinophil count and FeNO with depression and total HADS scores in the SAs group. The findings from this study confirmed higher rates of anxiety and depression in patients with severe asthma and using SomaScan found that certain inflammatory cytokines were significantly different in those patients, pointing to a possible underlying mechanism. SomaScan 05/03/ Slieker, RC. et al. Identification of biomarkers for glycaemic deterioration in type 2 diabetes Nat Commun. This study aimed to identify biomarkers for glycemic deteroriation in three type 2 diabetes cohorts encompassing 2,973 individuals across three molecular classes: metabolites, lipids and proteins. This represents the first study to use a multiomic approach for biomarker discovery and report systematically how metabolites of different classes impact progression of T2D. Individuals from three cohorts, DCS, GoDARTS and ANDIS were included. Protein data was generated using SomaScan 1.3k. In the investigated plasma proteins, the levels of 98 were nominally associated with time to insulin in the base model. The protein with the strongest association with time to insulin was GDF-15. Mendelian randomization was performed on six of the identified proteins to investigate casual associations. GDF15 is causally associated with diabetes progression and found a possible causal association for IL-18Ra and FAS. Metabolics data was generated using UHLPC-MS/MS. Two metabolites, Aminoadipic Acid (AADA) and Homocitrulline (Hcit) were significantly associated with diabetes progression. Lipid data was generated using mass spec. Nine lipids were associated with diabetes progression of which eight were associated with increased risk which all belonged to the Triacylglycerol (TAG) class. SomaStrengths: Biomarker identification, top proteins validated using ELISA SomaScan 05/03/ Maruszak, A. et al. Predicting progression to Alzheimer's disease with human hippocampal progenitors exposed to serum Brain In this study, the authors develop an in vitro model and a proteomic model using SomaScan data to predict progression of mild cognitive impairment (MCI) to Alzheimer’s disease using serum samples. Early intervention for Alzheimer’s disease is key and changes in hippocampal neurogenesis (HN) have been shown to be promising early markers for Alzheimer’s disease progression; however, results from previous studies have conflicting results on the directionality of those changes. Longitudinal studies are needed to address those discrepancies but are limited by the availability of viable techniques to study living human brains. In this study, an in vitro method to measure changes in HN is developed as a proxy by examining cell proliferation and differentiation of a human hippocampal progenitor cell line treated with longitudinal serum samples from MCI converters and non-converters. Cells treated with serum from MCI converters lead to decreased proliferation, increased cell death and increased neurogenesis. Using this in vitro system, a model was developed combining cell number, markers for cell proliferation, markers for cell differentiation, and education in years that was able to predict progression from MCI to Alzheimer’s with an AUC of 0.967 and an ability to predict disease progression up to 3.5 years before clinical diagnosis. Next, proteomics was employed to similarly explore development of a predictive model for conversion from MCI to Alzheimer’s. Samples were analyzed on SomaScan to measure unique proteins ( different protein epitopes) and, using machine learning, a panel of 15 proteins was identified that could distinguish between serum samples from MCI converters and non-converters with an AUC of 0.77. Pathway and network analysis was also performed on the differentially expressed proteins from the SomaScan data. Canonical pathways identified included Coagulation, Acute phase response signaling, Extrinsic prothrombin activation pathway, FXR/RXR activation, Notch signaling, Superpathway of methionine degradation, and Wnt/_-catenin Signaling. The top three networks identified were “Hematological System Development and Function, Organismal Functions, Organismal Injury and Abnormalities”, “Cell Death and Survival, Embryonic Development, Organismal Development”, and “Cell-to-Cell Signaling and Interaction, Cellular Function and Maintenance, Inflammatory Response”. This study demonstrates promising in vitro serum based models for predicting Alzheimer’s disease progression and provides insights into the underlying mechanisms of the disease in relation to changes in HN. SomaScan 05/02/ Butler, A. et al. High density lipoprotein-associated proteins in non-obese women with and without polycystic ovary syndrome Front Endocrinol. SomaScan 04/26/ Su CY. et al. Circulating proteins to predict COVID-19 severity Sci Rep. SomaScan 04/17/ Hwang M. et al. Quantitative proteomic screening uncovers candidate diagnostic and monitoring serum biomarkers of ankylosing spondylitis Arthritis Res Ther. SomaScan 04/11/ Govaere O. et al. A proteo-transcriptomic map of non-alcoholic fatty liver disease signatures Nat Metab. SomaScan 04/10/ Omenn G. et al. The Report on the Human Proteome from the HUPO Human Proteome Project J Proteome Res. SomaScan 04/07/ Xu Y. et al. An atlas of genetic scores to predict multi-omic traits Nature SomaScan Hirohama D. et al. Unbiased Human Kidney Tissue Proteomics Identifies Matrix Metalloproteinase 7 as a Kidney Disease Biomarker J Am Soc Nephrol. SomaScan 04/05/ Gomez-Lopez, N. et al. Pregnancy-specific responses to COVID-19 revealed by high-throughput proteomics of human plasma Commun Med (Lond) SomaScan 04/04/ Kalani R. et al. Plasma Proteomic Associations With Incident Ischemic Stroke in Older Adults: The Cardiovascular Health Study Neurology SomaScan 04/04/ Kim H. et al. Identification of Protein Biomarkers of the Dietary Approaches to Stop Hypertension Diet in Randomized Feeding Studies and Validation in an Observational Study J Am Heart Assoc. SomaScan 04/04/ Deo R. et al. Proteomic cardiovascular risk assessment in chronic kidney disease Eur Heart J. SomaScan 04/23/ Zhao Q. et al. Proteome and genome integration analysis of obesity Chinese Medical Journal SomaScan 03/31/ Perry TA. et al. Supportive Evidence For The Potential For Novel Biodiscovery In Osteoarthritis Through The Stepup Oa Consortium Osteoarthritis and Cartilage SomaScan Habet V. et al. Integrated Analysis of Tracheobronchial Fluid from Before and After Cardiopulmonary Bypass Reveals Activation of the Integrated Stress Response and Altered Pulmonary Microvascular Permeability Yale J Biol Med. SomaScan 03/31/ Vali Y. et al. Biomarkers for staging fibrosis and non-alcoholic steatohepatitis in non-alcoholic fatty liver disease (the LITMUS project): a comparative diagnostic accuracy study Lancet Gastroenterol Hepatol. SomaScan 03/20/ Wang S. et al. Associations between MICA and MICB genetic variants, protein levels, and colorectal cancer: Atherosclerosis Risk in Communities (ARIC) Cancer Epidemiol Biomarkers Prev. SomaScan 03/23/ Samorodnitsky S.et al. Lung proteome and metabolome endotype in HIV-associated obstructive lung disease ERJ Open Res. SomaScan 03/20/ Hooten NN et al. Plasma gelsolin levels are associated with diabetes, sex, race, and poverty J Transl Med. SomaScan 03/10/ Butler A. et al. HDL-Associated Proteins in Subjects with Polycystic Ovary Syndrome: A Proteomic Study Cells SomaScan 03/09/ Donlon T. et al. Proteomic basis of mortality resilience mediated by FOXO3 longevity genotype Geroscience SomaScan 03/07/ Moin ASM. et al. Coagulation factor dysregulation in polycystic ovary syndrome is an epiphenomenon of obesity Clin Endocrinol. (Oxf) SomaScan 03/01/ Emilsson OI, et al. Exhaled biomarkers in adults with non-productive cough Respir Res. SomaScan 03/01/ Berrone, E. et al. SOMAscan Proteomics Identifies Novel Plasma Proteins in Amyotrophic Lateral Sclerosis Patients Int J Mol Sci. SomaScan 01/18/ Chen, TK. et al. APOL1 Kidney Risk Variants and Proteomics Clin J Am Soc Nephrol. SomaScan 05/17/ Sher, A. et al. HLA-A, HSPA5, IGFBP5 and PSMA2 Are Restriction Factors for Zika Virus Growth in Astrocytic Cells Viruses SomaScan 12/29/ Naoko Sasamoto Plasma proteomic profiles of pain subtypes in adolescents and young adults with endometriosis Human Reproduction What are the similarities and differences in the systemic proteomic profiles by endometriosis-associated pain subtypes among adolescents and young adults with endometriosis? Naoko Sasamoto, Long Ngo, Allison F Vitonis, Simon T Dillon, Christine B Sieberg, Stacey A Missmer, Towia A Libermann, Kathryn L Terry SomaScan 05/17/ Itamar Sela Analytical validation of the PROphet computational model for clinical benefit prediction and decision-making tool in metastatic NSCLC bioRxiv https://doi.org/10./.04.20. Itamar Sela, Coren Lahav, Ben Yellin, Yehonatan Elon, Michal Harel SomaScan 04/24/ Chen-Yang Su Circulating proteins to predict COVID-19 severity Scientific Reports 13 https://doi.org/10./s-023--y Predicting COVID-19 severity is difficult, and the biological pathways involved are not fully understood. To approach this problem, we measured circulating human protein abundances in two independent cohorts totaling 986 individuals. We then trained prediction models including protein abundances and clinical risk factors to predict COVID-19 severity in 417 subjects and tested these models in a separate cohort of 569 individuals. For severe COVID-19, a baseline model including age and sex provided an area under the receiver operator curve (AUC) of 65% in the test cohort. Selecting 92 proteins from the unique protein abundances improved the AUC to 88% in the training cohort, which remained relatively stable in the testing cohort at 86%, suggesting good generalizability. Proteins selected from different COVID-19 severity were enriched for cytokine and cytokine receptors, but more than half of the enriched pathways were not immune-related. Taken together, these findings suggest that circulating proteins measured at early stages of disease progression are reasonably accurate predictors of COVID-19 severity. Further research is needed to understand how to incorporate protein measurement into clinical care. Chen-Yang Su, Sirui Zhou, Edgar Gonzalez-Kozlova, Guillaume Butler-Laporte, Elsa Brunet-Ratnasingham, Tomoko Nakanishi, Wonseok Jeon, David R. Morrison, Laetitia Laurent, Jonathan Afilalo, Marc Afilalo, Danielle Henry, Yiheng Chen, Julia Carrasco-Zanini, Yossi Farjoun, Maik Pietzner, Nofar Kimchi, Zaman Afrasiabi, Nardin Rezk, Meriem Bouab, Louis Petitjean, Charlotte Guzman, Xiaoqing Xue, Chris Tselios, Branka Vulesevic, Olumide Adeleye, Tala Abdullah, Noor Almamlouk, Yara Moussa, Chantal DeLuca, Naomi Duggan, Erwin Schurr, Nathalie Brassard, Madeleine Durand, Diane Marie Del Valle, Ryan Thompson, Mario A. Cedillo, Eric Schadt, Kai Nie, Nicole W. Simons, Konstantinos Mouskas, Nicolas Zaki, Manishkumar Patel, Hui Xie, Jocelyn Harris, Robert Marvin, Esther Cheng, Kevin Tuballes, Kimberly Argueta, Ieisha Scott, The Mount Sinai COVID-19 Biobank Team, Celia M. T. Greenwood, Clare Paterson, Michael A. Hinterberg, Claudia Langenberg, Vincenzo Forgetta, Joelle Pineau, Vincent Mooser, Thomas Marron, Noam D. Beckmann, Seunghee Kim-schulze, Alexander W. Charney, Sacha Gnjatic, Daniel E. Kaufmann, Miriam Merad & J. Brent Richards SomaScan 04/17/ Gisby J S, et al. Multi-omics identify falling LRRC15 as a COVID-19 severity marker and persistent pro-thrombotic signals in convalescence Nature Communications Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID19. Here, we perform longitudinal blood sampling of ESKD haemodialysis patients with COVID-19, collecting samples pre-infection, serially during infection, and after clinical recovery. Using plasma proteomics, and RNAsequencing and flow cytometry of immune cells, we identify transcriptomic and proteomic signatures of COVID-19 severity, and find distinct temporal molecular profiles in patients with severe disease. Jack S. Gisby, Norzawani B. Buiang, Artemis Papadaki, Candice L. Clarke, Talat H. Malik, Nicholas Medjeral-Thomas, Damiola Pinheiro, Page M. Mortimer, Shanice Lewis, Eleanor Sandhu, Stephen P McAdoo, Maria F. Prendecki, Michelle Willicombe, Matthew C. Pickering, Marina Botto, David C Thomas, James E. Peters SomaScan 12/15/ Yamada K, et al. Siglec-7 is a predictive biomarker for the efficacy of cancer vaccination against metastatic colorectal cancer Oncol Lett 21 1 10 https://doi.org/10./ol.. biomarker; colorectal cancer; peptide vaccine; protein expression analysis; sialic acid-binding immunoglobulin type lectin-7. Cancer immunotherapy, including vaccination, is considered a major scientific and medical breakthrough. However, cancer immunotherapy does not result in durable objective responses against colorectal cancer (CRC). To improve the efficacy of immunotherapy, the present study investigated several biomarkers for selecting patients who were expected to respond well to immunotherapy. Firstly, a comprehensive proteomic analysis was performed using tumor tissue lysates from patients enrolled in a phase II study, in which five human leukocyte antigen (HLA)-A*24:02-restricted peptides were administered. Sialic acid-binding immunoglobulin type lectin (Siglec)-7 was identified as a potential predictive biomarker. Subsequently, this biomarker was validated using western blot analysis, and immunofluorescence using tissue samples from the patients enrolled in the phase II study. The expression levels of Siglec-7 detected by immunofluorescence were quantified and their association with overall survival (OS) in patients treated with the peptide vaccine was examined. Furthermore, considering the important role of tumor-infiltrating lymphocytes (TILs) for CRC prognosis, the densities of CD3+, CD4+, CD8+ and forkhead box P3 (FOXP3)+ T cells in CRC tissues were examined and compared with Siglec-7 expression. The mean expression levels of Siglec-7 were significantly higher in patients with poor prognosis, with an OS of ≤2 years, as shown in comprehensive proteomic analysis (P=0.016) and western blot analysis (P=0.025). Immunofluorescence analysis demonstrated that Siglec-7 was expressed in intratumoral macrophages. The OS in patients with high Siglec-7 expression was significantly shorter than in that in patients with low Siglec-7 expression (P=0.017) in the HLA-A*24:02-matched patients. However, this difference was not observed in the HLA-unmatched patients. There was no significant difference in OS between patients according to the numbers of TILs, nor significant correlation between TILs and Siglec-7 expression. In conclusion, Siglec-7 expression in macrophages in tumor tissue may be a novel predictive biomarker for the efficacy of immunotherapy against metastatic CRC. Yamada K, Hazama S, Suzuki N, Xu M, Nakagami Y, Fujiwara N, Tsunedomi R, Yoshida S, Tomochika S, Matsukuma S, Matsui H, Tokumitsu Y, Kanekiyo S, Shindo Y, Watanabe Y, Iida M, Takeda S, Ioka T, Ueno T, Ogihara H, Hamamoto Y, Hoshii Y, Kawano H, Fujita T, Kawakami Y, Nagano H. SomaScan 11/03/ Blatt S, et al. High-Multiplex Aptamer-Based Serum Proteomics to Identify Candidate Serum Biomarkers of Oral Squamous Cell Carcinoma Cancers 15 7 https://doi.org/10./cancers oral cancer; SOMAscan; proteomics; liquid biopsy; biomarker; serum; prognosis; therapy Improved serological biomarkers are needed for the early detection, risk stratification and treatment surveillance of patients with oral squamous cell carcinoma (OSCC). We performed an exploratory study using advanced, highly specific, DNA-aptamer-based serum proteomics (SOMAscan, -plex) to identify distinct proteomic changes in patients with OSCC pre- vs. post-resection and compared to healthy controls. A total of 63 significantly differentially expressed serum proteins (each p human proteins to determine the impact of PSMA2 KD on A549 human lung epithelial cells. ... Meng Yu,  SomaScan 12/01/ Abdi IY, et al. Cross-sectional proteomic expression in Parkinson's disease-related proteins in drug-naive patients vs healthy controls with longitudinal clinical follow-up Neurobiol Dis There is an urgent need to find reliable and accessible blood-based biomarkers for early diagnosis of Parkinson's disease (PD) correlating with clinical symptoms and displaying predictive potential to improve future clinical trials. This led us to a conduct large-scale proteomics approach using an advanced high-throughput proteomics technology to create a proteomic profile for PD. Over proteins were measured in serum samples from a de novo Parkinson's (DeNoPa) cohort made up of 85 deep clinically phenotyped drug-naïve de novo PD patients and 93 matched healthy controls (HC) with longitudinal clinical follow-up available of up to 8 years.  Björn Österberg,  SomaScan 01/10/ Sykes R, et al. Adjudicated myocarditis and multisystem illness trajectory in healthcare workers post-COVID-19. Open Heart We investigated the associations of healthcare worker status with multisystem illness trajectory in hospitalised post-COVID-19 individuals. Muhammad Asghar,  SomaScan 02/10/ Rashid MU, et al. PSMA2 knockdown impacts expression of proteins involved in immune and cellular stress responses in human lung cells Biochim Biophys Acta Mol Basis Proteasome subunit alpha type-2 (PSMA2) is a critical component of the 20S proteasome, which is the core particle of the 26S proteasome complex and is involved in cellular protein quality control by recognizing and recycling defective proteins. PSMA2 expression dysregulation has been detected in different human diseases and viral infections. No study yet has reported PSMA2 knockdown (KD) effects on the cellular proteome. Penn Whitley,  SomaScan 12/05/ G Yang, et al. Multi-omics studies in historically excluded populations: the road to equity Clinical Pharmacology & Therapeutics Over the past few decades, genomewide association studies (GWASs) have identified the specific genetics variants contributing to many complex diseases by testing millions of genetic variations across the human genome against a variety of phenotypes. However, GWASs are limited in their ability to uncover mechanistic insight given that most significant associations are found in non-coding region of the genome. Jan Albert,  SomaScan 12/10/ R Dagher, et al. Proteomic profiling of serum identifies a molecular signature that correlates with clinical outcomes in COPD Plos One Novel biomarkers related to main clinical hallmarks of Chronic obstructive pulmonary disease (COPD), a heterogeneous disorder with pulmonary and extra-pulmonary manifestations, were investigated by profiling the serum levels of proteins using Slow Off-rate Modified Aptamers (SOMA)scan technology. Niclas Johansson,  SomaScan 12/08/ AK Cheema, et al. Radiation therapy induces innate immune responses in patients treated for prostate cancers Clinical Cancer Research Radiation therapy (RT) is a curative therapeutic modality used to treat cancers as a single agent or in combination with surgery and chemotherapy. Advanced RT technologies enable treatment with large fractions and highly conformal radiation doses to effect free-radical damage to cellular DNA leading to cell cycle arrest, cell death, and innate immune response (IIR) stimulation. Anna Färnert,  SomaScan 12/01/ P Kosa, et al. Molecular models of multiple sclerosis severity identify heterogeneity of pathogenic mechanisms Nature Communication While autopsy studies identify many abnormalities in the central nervous system (CNS) of subjects dying with neurological diseases, without their quantification in living subjects across the lifespan, pathogenic processes cannot be differentiated from epiphenomena. Using machine learning (ML), we searched for likely pathogenic mechanisms of multiple sclerosis (MS). Anna Smed-Sörensen SomaScan 12/12/ C Yang, et al. Mendelian randomization and genetic colocalization infer the effects of the multi-tissue proteome on 211 complex disease-related phenotypes Genome Medicine Human proteins are widely used as drug targets. Integration of large-scale protein-level genome-wide association studies (GWAS) and disease-related GWAS has thus connected genetic variation to disease mechanisms via protein. Previous proteome-by-phenome-wide Mendelian randomization (MR) studies have been mainly focused on plasma proteomes. C Yang, AM Fagan, RJ Perrin, H Rhinn, O Harari SomaScan 12/12/ Rooney Mary, et al. Comparison of Proteomic Measurements Across Platforms in the Atherosclerosis Risk in Communities (ARIC) Study. Clin Chem The plasma proteome can be quantified using different types of highly multiplexed technologies, including aptamer-based and proximity-extension immunoassay methods. There has been limited characterization of how these protein measurements correlate across platforms and with absolute measures from targeted immunoassays. Rooney MR, Chen J, Ballantyne CM, Hoogeveen RC, Tang O, Grams ME, Tin A, Ndumele CE, Zannad F, Couper DJ, Tang W, Selvin E, Coresh J. SomaScan 12/12/ Zhang Y, et al. Predicting AT(N) pathologies in Alzheimer's disease from blood-based proteomic data using neural networks. Front Aging Neurosci Blood-based biomarkers represent a promising approach to help identify early Alzheimer's disease (AD). Previous research has applied traditional machine learning (ML) to analyze plasma omics data and search for potential biomarkers, but the most modern ML methods based on deep learning has however been scarcely explored. In the current study, we aim to harness the power of state-of-the-art deep learning neural networks (NNs) to identify plasma proteins that predict amyloid, tau, and neurodegeneration (AT[N]) pathologies in AD. Zhang Y, Ghose U, Buckley NJ, Engelborghs S, Sleegers K, Frisoni GB, Wallin A, Lleó A, Popp J, Martinez-Lage P, Legido-Quigley C, Barkhof F, Zetterberg H, Visser PJ, Bertram L, Lovestone S, Nevado-Holgado AJ, Shi L. SomaScan 11/29/ Sanyal AJ, et al. Defining the serum proteomic signature of hepatic steatosis, inflammation, ballooning and fibrosis in nonalcoholic fatty liver disease. J Hepatol Despite recent progress, non-invasive tests for the diagnostic assessment and monitoring of non-alcoholic fatty liver disease (NAFLD) remain an unmet need. Herein, we aimed to identify diagnostic signatures of the key histological features of NAFLD. Sanyal AJ, Williams SA, Lavine JE, Tetri B, Alexander L, Ostroff R, Biegel H, Kowdley K, Chalasani N, Dasarathy S, Diehl AM, Loomba R, Hameed B, Behling C, Kleiner DE, Karpen SJ, Williams J, Jia Y, Yates KP, Tonascia J. SomaScan 12/14/ Bonaroti J, et al. Plasma proteomics reveals early, broad release of chemokine, cytokine, TNF, and interferon mediators following trauma with delayed increases in a subset of chemokines and cytokines in patients that remain critically ill. Front Immunol Severe injury is known to cause a systemic cytokine storm that is associated with adverse outcomes. However, a comprehensive assessment of the time-dependent changes in circulating levels of a broad spectrum of protein immune mediators and soluble immune mediator receptors in severely injured trauma patients remains uncharacterized.  Bonaroti J, Billiar I, Moheimani H, Wu J, Namas R, Li S, Kar UK, Vodovotz Y, Neal MD, Sperry JL, Billiar TR. SomaScan 11/30/ Piera-Velazquez S, et al. Aptamer proteomics of serum exosomes from patients with Primary Raynaud's and patients with Raynaud's at risk of evolving into Systemic Sclerosis. PLoS One A major unmet need for Systemic Sclerosis (SSc) clinical management is the lack of biomarkers for the early diagnosis of patients with Raynaud's Phenomenon at high risk of evolving into SSc. Piera-Velazquez S, Dillon ST, Gu X, Libermann TA, Jimenez SA. SomaScan 12/22/ Sanges S, et al. Biomarkers of haemodynamic severity of systemic sclerosis-associated pulmonary arterial hypertension by serum proteome analysis. Ann Rheum Dis To mine the serum proteome of patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) and to detect biomarkers that may assist in earlier and more effective diagnosis and treatment. Sanges S, Rice L, Tu L, Valenzi E, Cracowski JL, Montani D, Mantero JC, Ternynck C, Marot G, Bujor AM, Hachulla E, Launay D, Humbert M, Guignabert C, Lafyatis R. SomaScan 12/05/ Abu Saleh Md Moin, et al. Classical and alternate complement factor overexpression in non-obese weight matched women with polycystic ovary syndrome does not correlate with vitamin D. Front Endocrinol (Lausanne) Women with polycystic ovary syndrome (PCOS) exhibit complement factor expression changes that may be obesity-driven rather than an intrinsic facet of PCOS; furthermore, complement changes have been associated with vitamin D deficiency, a common feature of PCOS. Therefore, complement pathway proteins and vitamin D levels may be linked in PCOS. Abu Saleh Md Moin 1, Thozhukat Sathyapalan 2, Alexandra E Butler 1, Stephen L Atkin 1 SomaScan 12/31/ Pesutti CL, et al. Differential Proteins Expression Distinguished Between Patients With Infectious and Noninfectious Uveitis. Ocul Immunol Inflamm We investigated the aqueous humor proteome and associated plasma proteome in patients with infectious or noninfectious uveitis. Pessuti CL, Medley QG, Li N, Huang CL, Loureiro J, Banks A, Zhang Q, Costa DF, Ribeiro KS, Nascimento H, Muccioli C, Commodaro AG, Huang Q, Belfort R Jr. SomaScan 01/13/ Shuo Wang, et al. Abstract A022: Proteomic age acceleration associated with all-cause mortality in cancer survivors in the Atherosclerosis Risk in Communities (ARIC) Study.[R] Cancer Research Longer lifespan and improved cancer treatment led to a rapid rise in the number of cancer survivors. However, many cancer survivors have physiological dysregulations at earlier chronological ages than those without cancer, suggesting that cancer survivors’ biological age is higher than their chronological age, i.e., they have accelerated aging. Cancer survivors’ biological age may be estimated by a novel proteomic aging clock (PAC). Shuo Wang SomaScan 01/15/ Accortt E, et al. Perinatal Mood and Anxiety Disorders: biomarker discovery using plasma proteomics. Am J Obstet Gynecol Perinatal mood and anxiety disorders encompass a range of mental health disorders that occur during pregnancy and up to 1 year postpartum, affecting approximately 20% of women. Traditional risk factors, such as a history of depression and pregnancy complications including preeclampsia, are known. Their predictive utility, however, is not specific or sensitive enough to inform clinical decision-making or prevention strategies for perinatal mood and anxiety disorders. Better diagnostic and prognostic models are needed for early identification and referral to treatment. Accortt E, Mirocha J, Zhang D, Kilpatrick SJ, Libermann T, Karumanchi SA. SomaScan 01/14/ Rooney Mary, et al. Proteomic Predictors of Incident Diabetes: Results From the Atherosclerosis Risk in Communities (ARIC) Study Diabetes Care The plasma proteome preceding diabetes can improve our understanding of diabetes pathogenesis. SomaScan 01/27/ Winchester L, et al. Identification of a possible proteomic biomarker in Parkinson's disease: discovery and replication in blood, brain and cerebrospinal fluid. Brain Commun Biomarkers to aid diagnosis and delineate the progression of Parkinson's disease are vital for targeting treatment in the early phases of the disease. Here, we aim to discover a multi-protein panel representative of Parkinson's and make mechanistic inferences from protein expression profiles within the broader objective of finding novel biomarkers. Winchester L, Barber I, Lawton M, Ash J, Liu B, Evetts S, Hopkins-Jones L, Lewis S, Bresner C, Malpartida AB, Williams N, Gentlemen S, Wade-Martins R, Ryan B, Holgado-Nevado A, Hu M, Ben-Shlomo Y, Grosset D, Lovestone S. SomaScan 12/28/ Bakinowska L, et al. Exocrine Proteins Including Trypsin(ogen) as a Key Biomarker in Type 1 Diabetes. Diabetes Care Diabetes Proteomic profiling can identify useful biomarkers. Monozygotic (MZ) twins discordant for a condition represent an ideal test population. We aimed to investigate and validate proteomic profiling in twins with type 1 diabetes and in other well-characterized cohorts. Bakinowska L, Vartak T, Phuthego T, Taylor M, Chandler K, Jerram ST, Williams S, Feldmann M, Johnson DG, Patel KA, Williams AJK, Long AE, Leslie RD, Gillespie KM; Action LADA Consortium and BOX Study Group. SomaScan 01/26/ Dubin RF, et al. Analytical and Biological Variability of a Commercial Modified Aptamer Assay in Plasma Samples of Patients with Chronic Kidney Disease. J Appl Lab Med We carried out a study of the aptamer proteomic assay, SomaScan V4, to evaluate the analytical and biological variability of the assay in plasma samples of patients with moderate to severe chronic kidney disease (CKD). Dubin RF, Deo R, Ren Y, Lee H, Shou H, Feldman H, Kimmel P, Waikar SS, Rhee EP, Tin A, Chen J, Coresh J, Go AS, Kelly T, Rao PS, Chen TK, Segal MR, Ganz P. SomaScan 01/27/ Bellocchi C et al. Proteomic aptamer analysis reveals serum markers that characterize preclinical systemic sclerosis (SSc) patients at risk for progression toward definite SSc. Arthritis Res Ther. Bellocchi C, Assassi S, Lyons M, Marchini M, Mohan C, Santaniello A, Beretta L. SomaScan Sharma, M, et al. Abstract WMP101: Plasma Proteomic Determinants Of White Matter Hyperintensities And Covert Brain Infarction In The Cardiovascular Health Study Stroke Identification of novel biomarkers of cerebral small vessel disease is critical to elucidate pathophysiology and guide therapeutic development for prevention. We evaluated plasma proteomic associations of clinically asymptomatic … M Sharma, WT Longstreth, R Kalani, B Psaty, M Elkind SomaScan A Natu Aptamer-Based Plasma Proteomics Nominates Biomarkers Of Neurological Severity, Stroke Diagnosis And Age Stroke Plasma protein biomarkers measured in the hyperacute setting that are associated with stroke diagnosis or with clinical neurological severity, can be diagnostically and prognostically meaningful in patient care. We hypothesized that … A Natu, P Kumar, MR Frankel, S RANGARAJU SomaScan T Tanaka Proteomic Mediators of Overall Cardiovascular Health on All-Cause Mortality Nutrients … The hybridization controls, viral proteins, and flagged SOMAmer Reagents were removed, resulting in a total of SOMAmer Reagents that were used in the final analysis. Some of the SOMAmer Reagents are designed to capture multiplex … T Tanaka, SA Talegawkar, Y Jin, J Candia, G Fantoni… - Nutrients, SomaScan Gelinas AD Broadly neutralizing aptamers to SARS-CoV-2: a diverse panel of modified DNA antiviral agents. Mol Ther Nucleic Acids Gelinas AD, Tan TK, Liu S, Jaramillo JG, Chadwick J, Harding AC, Zhang C, Ream BE, Chase CN, Otis MR, Lee T, Schneider DJ, James WS, Janjic N. SomaScan Jozefczuk E, et al. Novel biomarkers and emerging tools to identify causal molecular pathways in hypertension and associated cardiovascular diseases. Kardiol Pol Józefczuk E, Guzik TJ, Siedlinski M. SomaScan Pierson SK, et al. CXCL13 is a predictive biomarker in idiopathic multicentric Castleman disease Nat Commun 13 1 https://www.doi.org/10./s-022--7 36,433,996 Humans *Castleman Disease/drug therapy Biomarkers Healthy Volunteers Immunotherapy Chemokine CXCL13 Idiopathic multicentric Castleman disease (iMCD) is a rare and poorly-understood cytokine storm-driven inflammatory disorder. Interleukin-6 (IL-6) is a known disease driver in some patients, but anti-IL-6 therapy with siltuximab is not effective in all patients, and biomarkers indicating success at an early time point following treatment initiation are lacking. Here we show, by comparison of levels of 1,178 proteins in sera of healthy participants (N = 42), patients with iMCD (N = 88), and with related diseases (N = 60), a comprehensive landscape of candidate disease mediators and predictors of siltuximab response. C-X-C Motif Chemokine Ligand-13 (CXCL13) is identified and validated as the protein most prominently up-regulated in iMCD. Early and significant decrease in CXCL13 levels clearly distinguishes siltuximab responders from non-responders; a 17% reduction by day 8 following siltuximab therapy initiation is predictive of response at later time points. Our study thus suggests that CXCL13 is a predictive biomarker of response to siltuximab in iMCD. Pierson, Sheila K Katz, Laura Williams, Reece Mumau, Melanie Gonzalez, Michael Guzman, Stacy Rubenstein, Ayelet Oromendia, Ana B Beineke, Philip Fossa, Alexander van Rhee, Frits Fajgenbaum, David C eng R01HL/U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ England Nat Commun. Nov 24;13(1):. doi: 10./s-022--7.I SomaScan 11/27/ Njunge JM, et al. The Childhood Acute Illness and Nutrition (CHAIN) network nested case-cohort study protocol: a multi-omics approach to understanding mortality among children in sub-Saharan Africa and South Asia Gates Open Res 6 77 https://www.doi.org/10./gatesopenres..2 36,415,883 Case-Cohort Children Lmic Mortality Omics Systems Biology Introduction: Many acutely ill children in low- and middle-income settings have a high risk of mortality both during and after hospitalisation despite guideline-based care. Understanding the biological mechanisms underpinning mortality may suggest optimal pathways to target for interventions to further reduce mortality. The Childhood Acute Illness and Nutrition (CHAIN) Network ( www.chainnnetwork.org) Nested Case-Cohort Study (CNCC) aims to investigate biological mechanisms leading to inpatient and post-discharge mortality through an integrated multi-omic approach. Methods and analysis; The CNCC comprises a subset of participants from the CHAIN cohort (/ hospitalised participants, including 350 children who died and 658 survivors, and 270/ well community children of similar age and household location) from nine sites in six countries across sub-Saharan Africa and South Asia. Systemic proteome, metabolome, lipidome, lipopolysaccharides, haemoglobin variants, toxins, pathogens, intestinal microbiome and biomarkers of enteropathy will be determined. Computational systems biology analysis will include machine learning and multivariate predictive modelling with stacked generalization approaches accounting for the different characteristics of each biological modality. This systems approach is anticipated to yield mechanistic insights, show interactions and behaviours of the components of biological entities, and help develop interventions to reduce mortality among acutely ill children. Ethics and dissemination. The CHAIN Network cohort and CNCC was approved by institutional review boards of all partner sites. Results will be published in open access, peer reviewed scientific journals and presented to academic and policy stakeholders. Data will be made publicly available, including uploading to recognised omics databases. Trial registration NCT. Njunge, James M Tickell, Kirkby Diallo, Abdoulaye Hama Sayeem Bin Shahid, Abu Sadat Mohammad Gazi, Md Amran Saleem, Ali Kazi, Zaubina Ali, Syed Tigoi, Caroline Mupere, Ezekiel Lancioni, Christina L Yoshioka, Emily Chisti, Mohammod Jobayer Mburu, Moses Ngari, Moses Ngao, Narshion Gichuki, Bonface Omer, Elisha Gumbi, Wilson Singa, Benson Bandsma, Robert Ahmed, Tahmeed Voskuijl, Wieger Williams, Thomas N Macharia, Alex Makale, Johnstone Mitchel, Anna Williams, Jessica Gogain, Joe Janjic, Nebojsa Mandal, Rupasri Wishart, David S Wu, Hang Xia, Lei Routledge, Michael Gong, Yun Yun Espinosa, Camilo Aghaeepour, Nima Liu, Jie Houpt, Eric Lawley, Trevor D Browne, Hilary Shao, Yan Rwigi, Doreen Kariuki, Kevin Kaburu, Timothy Uhlig, Holm H Gartner, Lisa Jones, Kelsey Koulman, Albert Walson, Judd Berkley, James eng Gates Open Res. Nov 3;6:77. doi: 10./gatesopenres..2. eCollection .I SomaScan 11/25/ Nawaz MS, et al. Thirty novel sequence variants impacting human intracranial volume Brain Commun 4 6 fcac271 https://www.doi.org/10./braincomms/fcac271 36,415,660 Mendelian randomization brain structure genetic correlation genome-wide association study intracranial volume Intracranial volume, measured through magnetic resonance imaging and/or estimated from head circumference, is heritable and correlates with cognitive traits and several neurological disorders. We performed a genome-wide association study meta-analysis of intracranial volume (n = 79 174) and found 64 associating sequence variants explaining 5.0% of its variance. We used coding variation, transcript and protein levels, to uncover 12 genes likely mediating the effect of these variants, including GLI3 and CDK6 that affect cranial synostosis and microcephaly, respectively. Intracranial volume correlates genetically with volumes of cortical and sub-cortical regions, cognition, learning, neonatal and neurological traits. Parkinson's disease cases have greater and attention deficit hyperactivity disorder cases smaller intracranial volume than controls. Our Mendelian randomization studies indicate that intracranial volume associated variants either increase the risk of Parkinson's disease and decrease the risk of attention deficit hyperactivity disorder and neuroticism or correlate closely with a confounder. Nawaz, Muhammad Sulaman Einarsson, Gudmundur Bustamante, Mariana Gisladottir, Rosa S Walters, G Bragi Jonsdottir, Gudrun A Skuladottir, Astros Th Bjornsdottir, Gyda Magnusson, Sigurdur H Asbjornsdottir, Bergrun Unnsteinsdottir, Unnur Sigurdsson, Engilbert Jonsson, Palmi V Palmadottir, Vala Kolbrun Gudjonsson, Sigurjon A Halldorsson, Gisli H Ferkingstad, Egil Jonsdottir, Ingileif Thorleifsson, Gudmar Holm, Hilma Thorsteinsdottir, Unnur Sulem, Patrick Gudbjartsson, Daniel F Stefansson, Hreinn Thorgeirsson, Thorgeir E Ulfarsson, Magnus O Stefansson, Kari eng England Brain Commun. Oct 25;4(6):fcac271. doi: 10./braincomms/fcac271. eCollection .I SomaScan 11/24/ Vorn R, et al. Are EPB41 and alpha-synuclein diagnostic biomarkers of sport-related concussion?Findings from the NCAA and Department of Defense CARE Consortium J Sport Health Sci epub ahead of print https://www.doi.org/10./j.jshs..11.007 36,403,906 Biomarkers College athletes Concussion Mild traumatic brain injury Sport injury BACKGROUND: Current protein biomarkers are only moderately predictive at identifying individuals with mild traumatic brain injury or concussion. Therefore, more accurate diagnostic markers are needed for sport-related concussion (SRC). METHODS: This was a multicenter, prospective, case-control study of athletes who provided blood samples and were diagnosed with a concussion or were a matched non-concussed control within the NCAA-DoD Concussion Assessment, Research, and Education (CARE) Consortium conducted between and . The blood was collected within 48 h of injury to identify protein abnormalities at the acute and subacute timepoints. Athletes with concussion were divided into 6 h post-injury (0-6 h post-injury) and after 6 h post-injury (7-48 hours post-injury) groups. We applied a highly multiplexed proteomic technique that used a DNA aptamers assay to target proteins in plasma samples from athletes with and without SRC. RESULTS: A total of 140 athletes with concussion (79.3% male; aged 18.71 +/- 1.10 years, mean +/- SD) and 21 non-concussed athletes (76.2% male; 19.14 +/- 1.10 years) were included in this study. We identified 338 plasma proteins that significantly differed in abundance (319 upregulated and 19 downregulated) in concussed athletes compared to non-concussed athletes. The top 20 most differentially abundant proteins discriminated concussed athletes from non-concussed athletes with an area under the curve (AUC) of 0.954 (95% confidence interval: 0.922_0.986). Specifically, after 6 h of injury, the individual AUC of plasma erythrocyte membrane protein band 4.1 (EPB41) and alpha-synuclein (SNCA) were 0.956 and 0.875, respectively. The combination of EPB41 and SNCA provided the best AUC (1.000), which suggests this combination of candidate plasma biomarkers is best for diagnosing concussion in athletes after 6 h of injury. CONCLUSION: Our data suggest that proteomic profiling may provide novel diagnostic protein markers and that a combination of EPB41 and SNCA is the most predictive biomarker of concussion after 6 h of injury. Vorn, Rany Devoto, Christina Meier, Timothy B Lai, Chen Yun, Sijung Broglio, Steven P Mithani, Sara McAllister, Thomas W Giza, Christopher C Kim, Hyung-Suk Huber, Daniel Harezlak, Jaroslaw Cameron, Kenneth L McGinty, Gerald Jackson, Jonathan Guskiewicz, Kevin M Mihalik, Jason P Brooks, Alison Duma, Stefan Rowson, Steven Nelson, Lindsay D Pasquina, Paul McCrea, Michael A Gill, Jessica M eng China J Sport Health Sci. Nov 17:S-(22)-4. doi: 10./j.jshs..11.007.I SomaScan 11/21/ Zaghlool SB, et al. Metabolic and proteomic signatures of type 2 diabetes subtypes in an Arab population Nat Commun 13 1 https://www.doi.org/10./s-022--z 36,402,758 Humans *Diabetes Mellitus, Type 2/genetics/metabolism Proteomics Arabs *Diabetes Mellitus, Type 1 Insulin Type 2 diabetes (T2D) has a heterogeneous etiology influencing its progression, treatment, and complications. A data driven cluster analysis in European individuals with T2D previously identified four subtypes: severe insulin deficient (SIDD), severe insulin resistant (SIRD), mild obesity-related (MOD), and mild age-related (MARD) diabetes. Here, the clustering approach was applied to individuals with T2D from the Qatar Biobank and validated in an independent set. Cluster-specific signatures of circulating metabolites and proteins were established, revealing subtype-specific molecular mechanisms, including activation of the complement system with features of autoimmune diabetes and reduced 1,5-anhydroglucitol in SIDD, impaired insulin signaling in SIRD, and elevated leptin and fatty acid binding protein levels in MOD. The MARD cluster was the healthiest with metabolomic and proteomic profiles most similar to the controls. We have translated the T2D subtypes to an Arab population and identified distinct molecular signatures to further our understanding of the etiology of these subtypes. Zaghlool, Shaza B Halama, Anna Stephan, Nisha Gudmundsdottir, Valborg Gudnason, Vilmundur Jennings, Lori L Thangam, Manonanthini Ahlqvist, Emma Malik, Rayaz A Albagha, Omar M E Abou-Samra, Abdul Badi Suhre, Karsten eng NPRP11C--/Qatar Foundation (Qatar Foundation for Education, Science and Community Development)/ England Nat Commun. Nov 19;13(1):. doi: 10./s-022--z.I SomaScan 11/20/ Dammer EB, et al. Multi-platform proteomic analysis of Alzheimer's disease cerebrospinal fluid and plasma reveals network biomarkers associated with proteostasis and the matrisome Alzheimers Res Ther 14 1 174 https://www.doi.org/10./s-022--5 36,384,809 Humans *Alzheimer Disease/cerebrospinal fluid Proteomics Proteostasis Amyloid beta-Peptides/cerebrospinal fluid Biomarkers/cerebrospinal fluid Robust and accessible biomarkers that can capture the heterogeneity of Alzheimer's disease and its diverse pathological processes are urgently needed. Here, we undertook an investigation of Alzheimer's disease cerebrospinal fluid (CSF) and plasma from the same subjects (n=18 control, n=18 AD) using three different proteomic platforms-SomaLogic SomaScan, Olink proximity extension assay, and tandem mass tag-based mass spectrometry-to assess which protein markers in these two biofluids may serve as reliable biomarkers of AD pathophysiology observed from unbiased brain proteomics studies. Median correlation of overlapping protein measurements across platforms in CSF (r~0.7) and plasma (r~0.6) was good, with more variability in plasma. The SomaScan technology provided the most measurements in plasma. Surprisingly, many proteins altered in AD CSF were found to be altered in the opposite direction in plasma, including important members of AD brain co-expression modules. An exception was SMOC1, a key member of the brain matrisome module associated with amyloid-beta deposition in AD, which was found to be elevated in both CSF and plasma. Protein co-expression analysis on greater than protein measurements in CSF and protein measurements in plasma across all proteomic platforms revealed strong changes in modules related to autophagy, ubiquitination, and sugar metabolism in CSF, and endocytosis and the matrisome in plasma. Cross-platform and cross-biofluid proteomics represents a promising approach for AD biomarker development. Dammer, Eric B Ping, Lingyan Duong, Duc M Modeste, Erica S Seyfried, Nicholas T Lah, James J Levey, Allan I Johnson, Erik C B eng K08 AG/AG/NIA NIH HHS/ P30 AG/AG/NIA NIH HHS/ U54 AG/AG/NIA NIH HHS/ England Alzheimers Res Ther. Nov 17;14(1):174. doi: 10./s-022--5.I SomaScan 11/18/ Carrasco-Zanini J, et al. Proteomic signatures for identification of impaired glucose tolerance Nat Med 28 11 - https://www.doi.org/10./s-022--z 36,357,677 Humans *Glucose Intolerance/diagnosis *Diabetes Mellitus, Type 2/diagnosis Blood Glucose/metabolism Proteomics Glucose Tolerance Test Fasting The implementation of recommendations for type 2 diabetes (T2D) screening and diagnosis focuses on the measurement of glycated hemoglobin (HbA1c) and fasting glucose. This approach leaves a large number of individuals with isolated impaired glucose tolerance (iIGT), who are only detectable through oral glucose tolerance tests (OGTTs), at risk of diabetes and its severe complications. We applied machine learning to the proteomic profiles of a single fasted sample from 11,546 participants of the Fenland study to test discrimination of iIGT defined using the gold-standard OGTTs. We observed significantly improved discriminative performance by adding only three proteins (RTN4R, CBPM and GHR) to the best clinical model (AUROC = 0.80 (95% confidence interval: 0.79-0.86), P = 0.004), which we validated in an external cohort. Increased plasma levels of these candidate proteins were associated with an increased risk for future T2D in an independent cohort and were also increased in individuals genetically susceptible to impaired glucose homeostasis and T2D. Assessment of a limited number of proteins can identify individuals likely to be missed by current diagnostic strategies and at high risk of T2D and its complications. Carrasco-Zanini, Julia Pietzner, Maik Lindbohm, Joni V Wheeler, Eleanor Oerton, Erin Kerrison, Nicola Simpson, Missy Westacott, Matthew Drolet, Dan Kivimaki, Mika Ostroff, Rachel Williams, Stephen A Wareham, Nicholas J Langenberg, Claudia eng MC_UU_/1/RCUK | Medical Research Council (MRC)/ R/RCUK | Medical Research Council (MRC)/ MC_PC_/RCUK | Medical Research Council (MRC)/ /Z/19/Z/Wellcome Trust (Wellcome)/ /Z/20/Z/Wellcome Trust (Wellcome)/ /Academy of Finland (Suomen Akatemia)/ /Academy of Finland (Suomen Akatemia)/ Nat Med. Nov;28(11):-. doi: 10./s-022--z. Epub Nov 10.I SomaScan 11/11/ Png G, et al. Identifying causal serum protein-cardiometabolic trait relationships using whole genome sequencing Hum Mol Genet epub ahead of print https://www.doi.org/10./hmg/ddac275 36,349,687 Cardiometabolic diseases, such as type 2 diabetes and cardiovascular disease, have a high public health burden. Understanding the genetically-determined regulation of proteins that are dysregulated in disease can help to dissect the complex biology underpinning them. Here, we perform a protein quantitative trait locus (pQTL) analysis of 255 serum proteins relevant to cardiometabolic processes in individuals. Meta-analysing whole-genome sequencing (WGS) data from two Greek cohorts, MANOLIS (n = ; 22.5x WGS) and Pomak (n = ; 18.4x WGS), we detect 302 independently-associated pQTL variants for 171 proteins, including 12 rare variants (minor allele frequency [MAF] 7,000 plasma proteins. IFNbeta-1a and pegIFNbeta-1a resulted in 248 and 528 differentially expressed protein analytes, respectively, between treatment and placebo groups over the time course. Thirty-one proteins were prioritized based on a maximal fold change >/= 2 from baseline, baseline adjusted area under the effect curve (AUEC) and overlap between the 2 products. Of these, the majority had a significant AUEC compared with placebo in response to either product; 8 proteins showed > 4-fold maximal change from baseline. We identified previously reported candidates, beta-2microglobulin and interferon-induced GTP-binding protein (Mx1) with ~ 50% coefficient of variation (CV) for AUEC, and many new candidates (including I-TAC, C1QC, and IP-10) with CVs ranging from 26%-129%. Upstream regulator analysis of differentially expressed proteins predicted activation of IFNbeta1 signaling as well as other cytokine, enzyme, and transcription signaling networks by both products. Although independent replication is required to confirm present results, our study demonstrates the utility of proteomics for the identification of individual and composite candidate PD biomarkers that may be leveraged to support clinical pharmacology studies for biosimilar approvals, especially when biologics have complex mechanisms of action or do not have previously characterized PD biomarkers. Hyland, Paula L Chekka, Lakshmi Manasa S Samarth, Deepti P Rosenzweig, Barry A Decker, Erica Mohamed, Esraa G Guo, Yan Matta, Murali K Sun, Qin Wheeler, William Sanabria, Carlos Weaver, James L Schrieber, Sarah J Florian, Jeffry Wang, Yow-Ming Strauss, David G eng Clin Pharmacol Ther. Oct 29. doi: 10./cpt..I SomaScan 10/30/ Butler AE, et al. Components of the Complement Cascade Differ in Polycystic Ovary Syndrome Int J Mol Sci 23 20 https://www.doi.org/10./ijms 36,293,087 Female Humans Properdin/metabolism Complement Factor H Complement Factor B/metabolism *Mannose-Binding Lectin CD55 Antigens *Polycystic Ovary Syndrome Complement Factor D *Insulin Resistance Cohort Studies Proteomics Complement C1q Complement C3b Fibrinogen Cytokines C3 complement factors factor B polycystic ovary syndrome properdin Complement pathway proteins are reported to be increased in polycystic ovary syndrome (PCOS) and may be affected by obesity and insulin resistance. To investigate this, a proteomic analysis of the complement system was undertaken, including inhibitory proteins. In this cohort study, plasma was collected from 234 women (137 with PCOS and 97 controls). SOMALogic proteomic analysis was undertaken for the following complement system proteins: C1q, C1r, C2, C3, C3a, iC3b, C3b, C3d, C3adesArg, C4, C4a, C4b, C5, C5a, C5b-6 complex, C8, properdin, factor B, factor D, factor H, factor I, mannose-binding protein C (MBL), complement decay-accelerating factor (DAF) and complement factor H-related protein 5 (CFHR5). The alternative pathway of the complement system was primarily overexpressed in PCOS, with increased C3 (p 8,000 individuals, testican-2 is associated with kidney health and prognosis, with higher levels associated with reduced risk of ESKD. Wen, Donghai Zhou, Linda Zheng, Zihe Surapaneni, Aditya Ballantyne, Christie Hoogeveen, Ron Shlipak, Michael Waikar, Sushrut Vasan, Ramachandra Kimmel, Paul Dubin, Ruth Deo, Rajat Feldman, Harold Ganz, Peter Coresh, Josef Grams, Morgan Rhee, Eugene eng J Am Soc Nephrol. Oct 26:ASN.. doi: 10./ASN..I SomaScan 10/27/ Sveinbjornsson G, et al. Multiomics study of nonalcoholic fatty liver disease Nat Genet 54 11 - https://www.doi.org/10./s-022--5 36,280,732 Humans *Non-alcoholic Fatty Liver Disease/genetics Proteomics Genome-Wide Association Study Liver/metabolism Liver Cirrhosis/genetics/metabolism/pathology *Liver Neoplasms/genetics/metabolism Nonalcoholic fatty liver (NAFL) and its sequelae are growing health problems. We performed a genome-wide association study of NAFL, cirrhosis and hepatocellular carcinoma, and integrated the findings with expression and proteomic data. For NAFL, we utilized 9,491 clinical cases and proton density fat fraction extracted from 36,116 liver magnetic resonance images. We identified 18 sequence variants associated with NAFL and 4 with cirrhosis, and found rare, protective, predicted loss-of-function variants in MTARC1 and GPAM, underscoring them as potential drug targets. We leveraged messenger RNA expression, splicing and predicted coding effects to identify 16 putative causal genes, of which many are implicated in lipid metabolism. We analyzed levels of 4,907 plasma proteins in 35,559 Icelanders and 1,459 proteins in 47,151 UK Biobank participants, identifying multiple proteins involved in disease pathogenesis. We show that proteomics can discriminate between NAFL and cirrhosis. The present study provides insights into the development of noninvasive evaluation of NAFL and new therapeutic options. Sveinbjornsson, Gardar Ulfarsson, Magnus O Thorolfsdottir, Rosa B Jonsson, Benedikt A Einarsson, Eythor Gunnlaugsson, Gylfi Rognvaldsson, Solvi Arnar, David O Baldvinsson, Magnus Bjarnason, Ragnar G Eiriksdottir, Thjodbjorg Erikstrup, Christian Ferkingstad, Egil Halldorsson, Gisli H Helgason, Hannes Helgadottir, Anna Hindhede, Lotte Hjorleifsson, Grimur Jones, David Knowlton, Kirk U Lund, Sigrun H Melsted, Pall Norland, Kristjan Olafsson, Isleifur Olafsson, Sigurdur Oskarsson, Gudjon R Ostrowski, Sisse Rye Pedersen, Ole Birger Snaebjarnarson, Auethunn S Sigurdsson, Emil Steinthorsdottir, Valgerdur Schwinn, Michael Thorgeirsson, Gudmundur Thorleifsson, Gudmar Jonsdottir, Ingileif Bundgaard, Henning Nadauld, Lincoln Bjornsson, Einar S Rulifson, Ingrid C Rafnar, Thorunn Norddahl, Gudmundur L Thorsteinsdottir, Unnur Sulem, Patrick Gudbjartsson, Daniel F Holm, Hilma Stefansson, Kari eng Nat Genet. Nov;54(11):-. doi: 10./s-022--5. Epub Oct 24.I SomaScan 10/26/ Lu T, et al. Circulating Proteins Influencing Psychiatric Disease: A Mendelian Randomization Study Biol Psychiatry epub ahead of print https://www.doi.org/10./j.biopsych..08.015 36,280,454 Blood-brain barrier Circulating proteins Genome-wide association studies Mendelian randomization Psychiatric diseases Quantitative trait loci BACKGROUND: There is a pressing need for novel drug targets for psychiatric disorders. Circulating proteins are potential candidates because they are relatively easy to measure and modulate and play important roles in signaling. METHODS: We performed two-sample Mendelian randomization analyses to estimate the associations between circulating protein abundances and risk of 10 psychiatric disorders. Genetic variants associated with circulating protein abundances identified in 6 large-scale proteomic studies were used as genetic instruments. Effects of the circulating proteins on psychiatric disorders were estimated by Wald ratio or inverse variance-weighted ratio tests. Horizontal pleiotropy, colocalization, and protein-altering effects were examined to validate the assumptions of Mendelian randomization. RESULTS: Nine circulating protein-to-disease associations withstood multiple sensitivity analyses. Among them, 2 circulating proteins had associations replicated in 3 proteomic studies. A 1 standard deviation increase in the genetically predicted circulating TIMP4 level was associated with a reduced risk of anorexia nervosa (minimum odds ratio [OR] = 0.83; 95% CI, 0.76-0.91) and bipolar disorder (minimum OR = 0.88; 95% CI, 0.82-0.94). A 1 standard deviation increase in the genetically predicted circulating ESAM level was associated with an increased risk of schizophrenia (maximum OR = 1.32; 95% CI, 1.22-1.43). In addition, 58 suggestive protein-to-disease associations warrant validation with observational or experimental evidence. For instance, a 1 standard deviation increase in the ERLEC1-201-to-ERLEC1-202 splice variant ratio was associated with a reduced risk of schizophrenia (OR = 0.94; 95% CI, 0.90-0.97). CONCLUSIONS: Prioritized circulating proteins appear to influence the risk of psychiatric disease and may be explored as intervention targets. Lu, Tianyuan Forgetta, Vincenzo Greenwood, Celia M T Zhou, Sirui Richards, J Brent eng Biol Psychiatry. Aug 22:S-(22)-4. doi: 10./j.biopsych..08.015.I SomaScan 10/25/ Mofrad RB, et al. Plasma proteome profiling identifies changes associated to AD but not to FTD Acta Neuropathol Commun 10 1 148 https://www.doi.org/10./s-022--w 36,273,219 Humans Female Middle Aged Aged Male *Frontotemporal Dementia/diagnosis/genetics Proteome Proteomics *Frontotemporal Lobar Degeneration/diagnosis/pathology *Pick Disease of the Brain Biomarkers Ad Alzheimer's disease Ftd Frontotemporal dementia Plasma biomarkers Somascan BACKGROUND: Frontotemporal dementia (FTD) is caused by frontotemporal lobar degeneration (FTLD), characterized mainly by inclusions of Tau (FTLD-Tau) or TAR DNA binding43 (FTLD-TDP) proteins. Plasma biomarkers are strongly needed for specific diagnosis and potential treatment monitoring of FTD. We aimed to identify specific FTD plasma biomarker profiles discriminating FTD from AD and controls, and between FTD pathological subtypes. In addition, we compared plasma results with results in post-mortem frontal cortex of FTD cases to understand the underlying process. METHODS: Plasma proteins (n = ) from pathologically and/or genetically confirmed FTD patients (n = 56; FTLD-Tau n = 16; age = 58.2 +/- 6.2; 44% female, FTLD-TDP n = 40; age = 59.8 +/- 7.9; 45% female), AD patients (n = 57; age = 65.5 +/- 8.0; 39% female), and non-demented controls (n = 148; 61.3 +/- 7.9; 41% female) were measured using an aptamer-based proteomic technology (SomaScan). In addition, exploratory analysis in post-mortem frontal brain cortex of FTD (n = 10; FTLD-Tau n = 5; age = 56.2 +/- 6.9, 60% female, and FTLD-TDP n = 5; age = 64.0 +/- 7.7, 60% female) and non-demented controls (n = 4; age = 61.3 +/- 8.1; 75% female) were also performed. Differentially regulated plasma and tissue proteins were identified by global testing adjusting for demographic variables and multiple testing. Logistic lasso regression was used to identify plasma protein panels discriminating FTD from non-demented controls and AD, or FTLD-Tau from FTLD-TDP. Performance of the discriminatory plasma protein panels was based on predictions obtained from bootstrapping with resampled analysis. RESULTS: Overall plasma protein expression profiles differed between FTD, AD and controls (6 proteins; p = 0.005), but none of the plasma proteins was specifically associated to FTD. The overall tissue protein expression profile differed between FTD and controls (7-proteins; p = 0.003). There was no difference in overall plasma or tissue expression profile between FTD subtypes. Regression analysis revealed a panel of 12-plasma proteins discriminating FTD from AD with high accuracy (AUC: 0.99). No plasma protein panels discriminating FTD from controls or FTD pathological subtypes were identified. CONCLUSIONS: We identified a promising plasma protein panel as a minimally-invasive tool to aid in the differential diagnosis of FTD from AD, which was primarily associated to AD pathophysiology. The lack of plasma profiles specifically associated to FTD or its pathological subtypes might be explained by FTD heterogeneity, calling for FTD studies using large and well-characterize cohorts. Mofrad, R Babapour Del Campo, M Peeters, C F W Meeter, L H H Seelaar, H Koel-Simmelink, M Ramakers, I H G B Middelkoop, H A M De Deyn, P P Claassen, J A H R van Swieten, J C Bridel, C Hoozemans, J J M Scheltens, P van der Flier, W M Pijnenburg, Y A L Teunissen, Charlotte E eng /ZONMW_/ZonMw/Netherlands ToBike4Alzheimer/Alzheimer Nederland/ England Acta Neuropathol Commun. Oct 22;10(1):148. doi: 10./s-022--w.I SomaScan 10/24/ Cai Y, et al. Association of mTORC1_dependent circulating protein levels with cataract formation: a mendelian randomization study BMC Genomics 23 1 719 https://www.doi.org/10./s-022--7 36,271,348 Humans *Cataract/genetics Eukaryotic Initiation Factor-4A Eukaryotic Initiation Factor-4E/genetics *Eukaryotic Initiation Factor-4G Genome-Wide Association Study Mechanistic Target of Rapamycin Complex 1/genetics Mendelian Randomization Analysis Polymorphism, Single Nucleotide Sirolimus TOR Serine-Threonine Kinases/genetics Cataract Circulating Eif4ebp Mendelian randomization mTOR BACKGROUND: The mechanistic target of rapamycin (mTOR) signal pathway plays a critical regulating role in the occurrence and development of cataract. However, the role of mTORC1 downstream proteins, including ribosomal protein S6K (RP-S6K), eukaryotic initiation factor 4E-binding protein (EIF4EBP), eukaryotic initiation factor 4G (EIF-4G), eukaryotic initiation factor 4E (EIF-4E), and eukaryotic initiation factor 4A (EIF-4A), in regulating cataract development is still unknown. Herein, we conducted a mendelian randomization (MR) study to understand the function of mTORC1 signaling in the process of cataract development. RESULTS: The causal estimate was evaluated with inverse-variance weighted (IVW) estimate, weighted median estimator, MR-Egger and MR robust adjusted profile score (MR. RAPS). The single-nucleotide polymorphisms (SNPs), P 5.2 x 10(9)/L) had a significantly increased chance of requiring IMT during follow-up (hazard ratio, 3.2; 95% confidence interval, 1.5-6.8; P = 0.002). We validated these findings in a third cohort of 67 United States patients. CONCLUSIONS: A serum protein signature correlating with neutrophil levels was highly predictive for IMT use in noninfectious uveitis. We developed a routinely available tool that may serve as a novel objective biomarker to aid in clinical decision-making for noninfectious uveitis. Kuiper, Jonas J W Verhagen, Fleurieke H Hiddingh, Sanne Wennink, Roos A W Hansen, Anna M Casey, Kerry A Hoefer, Imo E Haitjema, Saskia Drylewicz, Julia Yakin, Mehmet Sen, H Nida Radstake, Timothy R D J de Boer, Joke H eng Netherlands Ophthalmol Sci. May 31;2(3):. doi: 10./j.xops... eCollection Sep.I SomaScan 10/18/ Candia J, et al. Assessment of variability in the plasma 7k SomaScan proteomics assay Sci Rep 12 1 https://www.doi.org/10./s-022--0 36,229,504 Biomarkers/metabolism Humans *Proteomics/methods SomaScan is a high-throughput, aptamer-based proteomics assay designed for the simultaneous measurement of thousands of proteins with a broad range of endogenous concentrations. In its most current version, the 7k SomaScan assay v4.1 is capable of measuring human proteins. In this work, we present an extensive technical assessment of this platform based on a study of samples across 22 plates. Included in the study design were inter-plate technical duplicates from 102 human subjects, which allowed us to characterize different normalization procedures, evaluate assay variability by multiple analytical approaches, present signal-over-background metrics, and discuss potential specificity issues. By providing detailed performance assessments on this wide range of technical aspects, we aim for this work to serve as a valuable resource for the growing community of SomaScan users. Candia, Julian Daya, Gulzar N Tanaka, Toshiko Ferrucci, Luigi Walker, Keenan A eng ZIAAG-14/AG/NIA NIH HHS/ ZIAAG-01/AG/NIA NIH HHS/ England Sci Rep. Oct 13;12(1):. doi: 10./s-022--0.I SomaScan 10/14/ Moin ASM, et al. The severity and duration of Hypoglycemia affect platelet-derived protein responses in Caucasians Cardiovasc Diabetol 21 1 202 https://www.doi.org/10./s-022--w 36,203,210 Blood Glucose/metabolism CD40 Ligand *Diabetes Mellitus, Type 2/diagnosis Humans *Hypoglycemia Plasminogen Plasminogen Activator Inhibitor 1 Thromboplastin von Willebrand Factor Hypoglycemia Inflammation Platelet-associated proteins Type 2 diabetes conflict of interest or competing interests to declare. OBJECTIVE: Severe hypoglycemia is associated with increased cardiovascular death risk, and platelet responses to hypoglycemia (hypo) have been described. However, the impact of deep transient hypo (deep-hypo) versus prolonged milder hypo (mild-hypo) on platelet response is unclear. RESEARCH DESIGN AND METHODS: Two hypo studies were compared; firstly, mild-hypo in 18-subjects (10 type-2-diabetes (T2D), 8 controls), blood glucose to 2.8mmoL/L (50 mg/dL) for 1-hour; secondly deep-hypo in 46-subjects (23 T2D, 23 controls), blood glucose to 1.5 (INR-TIC), TEG maximum amplitude 10 units of red blood cells in 24 hours or > 4 units RBC/hour during the first 4 hr. SomaLogic proteomic analysis of 1,305 proteins was performed. Pathways associated with proteins dysregulated in patients with each TIC definition and MT were identified. RESULTS: Patients (n=211) had a mean injury severity score of 24, with a MT and mortality rate of 22% and 12%, respectively. We identified 578 SOMAscan analytes dysregulated among MT patients, of which INR-TIC, TEG-TIC, and Clin-TIC patients showed dysregulation only in 25%, 3%, and 4% of these, respectively. TIC definitions jointly failed to show changes in 73% of the protein levels associated with MT, and failed to identify 26% of patients that received a massive transfusion. INR-TIC and TEG-TIC patients showed dysregulation of proteins significantly associated with complement activity. Proteins dysregulated in Clin-TIC or massive transfusion patients were not significantly associated with any pathway. CONCLUSION: These data indicate there are unexplored opportunities to identify patients at risk for massive bleeding. Only a small subset of proteins that are dysregulated in patients receiving MT are statistically significantly dysregulated among patients whose TIC is defined based solely on laboratory measurements or clinical assessment. Moore, Hunter B Neal, Matthew D Bertolet, Marnie Joughin, Brian A Yaffe, Michael B Barrett, Christopher D Bird, Molly A Tracy, Russell P Moore, Ernest E Sperry, Jason L Zuckerbraun, Brian S Park, Myung S Cohen, Mitchell J Wisniewski, Stephen R Morrissey, James H eng R00 HL/HL/NHLBI NIH HHS/ R35 GM/GM/NIGMS NIH HHS/ R35 HL/HL/NHLBI NIH HHS/ K99 HL/HL/NHLBI NIH HHS/ UM1 HL/HL/NHLBI NIH HHS/ Ann Surg Open. Jun;3(2):e167. doi: 10./as9.. Epub May 25.I SomaScan 10/01/ Butler-Laporte G, et al. The dynamic changes and sex differences of 147 immune-related proteins during acute COVID-19 in 580 individuals Clin Proteomics 19 1 34 https://www.doi.org/10./s-022--z 36,171,541 Covid-19 Immunity Proteomics SOMAscan the Founder of 5 Prime Sciences. The Lady Davis Institute has previously received funding from GlaxoSmithKline, Eli Lilly, and Biogen for research programs at Dr. Richards' laboratory unrelated to this manuscript. C.P. and M.H. are employees of SomaLogic. INTRODUCTION: Severe COVID-19 leads to important changes in circulating immune-related proteins. To date it has been difficult to understand their temporal relationship and identify cytokines that are drivers of severe COVID-19 outcomes and underlie differences in outcomes between sexes. Here, we measured 147 immune-related proteins during acute COVID-19 to investigate these questions. METHODS: We measured circulating protein abundances using the SOMAscan nucleic acid aptamer panel in two large independent hospital-based COVID-19 cohorts in Canada and the United States. We fit generalized additive models with cubic splines from the start of symptom onset to identify protein levels over the first 14 days of infection which were different between severe cases and controls, adjusting for age and sex. Severe cases were defined as individuals with COVID-19 requiring invasive or non-invasive mechanical respiratory support. RESULTS: 580 individuals were included in the analysis. Mean subject age was 64.3 (sd 18.1), and 47% were male. Of the 147 proteins, 69 showed a significant difference between cases and controls (p 4-fold higher risk (odds ratio: 4.88; 95%-CI: 2.47-9.63; p-value /=14-days relative to recovery /= 15 vs. AHI 0.9). sTREM2 had a fair correlation (r > 0.6), whereas SNAP-25 showed weak correlation (r = 0.06). Measures in both platforms provided similar predicted performance for all biomarkers except SNAP-25 and one of the sTREM2 analytes. sTREM2 showed higher AUC for SOMAscan based measures. CONCLUSION: Our data indicate that SOMAscan performs as well as immunoassay approaches for NfL, Neurogranin, VILIP-1, and sTREM2. Our study shows promise for using SOMAscan as an alternative to traditional immunoassay-based measures. Follow-up investigation will be required for SNAP-25 and additional established biomarkers. Timsina, Jigyasha Gomez-Fonseca, Duber Wang, Lihua Do, Anh Western, Dan Alvarez, Ignacio Aguilar, Miquel Pastor, Pau Henson, Rachel L Herries, Elizabeth Xiong, Chengjie Schindler, Suzanne E Fagan, Anne M Bateman, Randall J Farlow, Martin Morris, John C Perrin, Richard J Moulder, Krista Hassenstab, Jason Voglein, Jonathan Chhatwal, Jasmeer Mori, Hiroshi Sung, Yun Ju Cruchaga, Carlos eng R01 AG/AG/NIA NIH HHS/ RF1 AG/AG/NIA NIH HHS/ RF1 AG/AG/NIA NIH HHS/ P01 AG/AG/NIA NIH HHS/ RF1 AG/AG/NIA NIH HHS/ P30 AG/AG/NIA NIH HHS/ P01 AG/AG/NIA NIH HHS/ U19 AG/AG/NIA NIH HHS/ Comparative Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Netherlands J Alzheimers Dis. ;89(1):193-207. doi: 10./JAD-.I SomaScan 07/25/ Surapaneni A, et al. Identification of 969 protein quantitative trait loci in an African American population with kidney disease attributed to hypertension Kidney Int 102 5 - https://www.doi.org/10./j.kint..07.005 35,870,639 Humans Quantitative Trait Loci African Americans/genetics Proteome Genome-Wide Association Study Polymorphism, Single Nucleotide *Hypertension/genetics *Kidney Diseases/genetics Genetic Predisposition to Disease pQTL protein quantitative trait loci Investigations into the causal underpinnings of disease processes can be aided by the incorporation of genetic information. Genetic studies require populations varied in both ancestry and prevalent disease in order to optimize discovery and ensure generalizability of findings to the global population. Here, we report the genetic determinants of the serum proteome in 466 African Americans with chronic kidney disease attributed to hypertension from the richly phenotyped African American Study of Kidney Disease and Hypertension (AASK) study. Using the largest aptamer-based protein profiling platform to date (6,790 proteins or protein complexes), we identified 969 genetic associations with 900 unique proteins; including 52 novel cis (local) associations and 379 novel trans (distant) associations. The genetic effects of previously published cis-protein quantitative trait loci (pQTLs) were found to be highly reproducible, and we found evidence that our novel genetic signals colocalize with gene expression and disease processes. Many trans- pQTLs were found to reflect associations mediated by the circulating cis protein, and the common trans-pQTLs are enriched for processes involving extracellular vesicles, highlighting a plausible mechanism for distal regulation of the levels of secreted proteins. Thus, our study generates a valuable resource of genetic associations linking variants to protein levels and disease in an understudied patient population to inform future studies of drug targets and physiology. Surapaneni, Aditya Schlosser, Pascal Zhou, Linda Liu, Celina Chatterjee, Nilanjan Arking, Dan E Dutta, Diptavo Coresh, Josef Rhee, Eugene P Grams, Morgan E eng Kidney Int. Nov;102(5):-. doi: 10./j.kint..07.005. Epub Jul 21.I SomaScan 07/24/ Luther J, et al. The circulating proteomic signature of alcohol-associated liver disease JCI Insight 7 14 https://www.doi.org/10./jci.insight. 35,866,482 Biomarkers Humans *Liver Diseases, Alcoholic/metabolism Proteome *Proteomics Hepatitis Hepatology Proteomics Despite being a leading cause of advanced liver disease, alcohol-associated liver disease (ALD) has no effective medical therapies. The circulating proteome, which comprises proteins secreted by different cells and tissues in the context of normal physiological function or in the setting of disease and illness, represents an attractive target for uncovering novel biology related to the pathogenesis of ALD. In this work, we used the aptamer-based SomaScan proteomics platform to quantify the relative concentration of over proteins in a well-characterized cohort of patients with the spectrum of ALD. We found a distinct circulating proteomic signature that correlated with ALD severity, including over 600 proteins that differed significantly between ALD stages, many of which have not previously been associated with ALD to our knowledge. Notably, certain proteins that were markedly dysregulated in patients with alcohol-associated hepatitis were also altered, to a lesser degree, in patients with subclinical ALD and may represent early biomarkers for disease progression. Taken together, our work highlights the vast and distinct changes in the circulating proteome across the wide spectrum of ALD, identifies potentially novel biomarkers and therapeutic targets, and provides a proteomic resource atlas for ALD researchers and clinicians. Luther, Jay Vannier, Augustin Gl Schaefer, Esperance A Goodman, Russell P eng K08 DK/DK/NIDDK NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't JCI Insight. Jul 22;7(14):e. doi: 10./jci.insight..I SomaScan 07/23/ Hedou J, et al. Proteomic biomarkers of Kleine-Levin syndrome Sleep 45 9 https://www.doi.org/10./sleep/zsac097 35,859,339 Biomarkers *Cognitive Dysfunction *Disorders of Excessive Somnolence Humans *Kleine-Levin Syndrome Proteomics Csf Kleine-Levine syndrome aptamers brain immunity hypersomnia microglia serum STUDY OBJECTIVES: Kleine-Levin syndrome (KLS) is characterized by relapsing-remitting episodes of hypersomnia, cognitive impairment, and behavioral disturbances. We quantified cerebrospinal fluid (CSF) and serum proteins in KLS cases and controls. METHODS: SomaScan was used to profile CSF proteins in 30 KLS cases and 134 controls, while serum proteins were profiled in serum from 26 cases and 65 controls. CSF and serum proteins were both measured in seven cases. Univariate and multivariate analyses were used to find differentially expressed proteins (DEPs). Pathway and tissue enrichment analyses (TEAs) were performed on DEPs. RESULTS: Univariate analyses found 28 and 141 proteins differentially expressed in CSF and serum, respectively (false discovery rate 50%) to explain the survival benefit of early TP in E2-TBI patients. The multivariate latent-factor regression analyses also uncovered 5 latent clusters of features with a proportion effect >30%, many in common with the observable features. Among the observable and latent features were protease inhibitors known to inhibit activated protein C and block fibrinolysis (SERPINA5 and CPB2), a clotting factor (factor XI), as well as proteins involved in lipid transport and metabolism (APOE3 and sPLA(2)-XIIA). CONCLUSIONS: These findings suggest that severely injured patients with TBI process exogenous plasma differently than those without TBI. The beneficial effects of early TP in E2-TBI patients may be the result of improved blood clotting and the effect of brain protective factors independent of coagulation. Wu, Junru Moheimani, Hamed Li, Shimena Kar, Upendra K Bonaroti, Jillian Miller, Richard S Daley, Brian J Harbrecht, Brian G Claridge, Jeffrey A Gruen, Danielle S Phelan, Herbert A Guyette, Francis X Neal, Matthew D Das, Jishnu Sperry, Jason L Billiar, Timothy R eng R35 GM/GM/NIGMS NIH HHS/ R01 HL/HL/NHLBI NIH HHS/ R38 HL/HL/NHLBI NIH HHS/ T32 GM/GM/NIGMS NIH HHS/ R35 GM/GM/NIGMS NIH HHS/ DP2 AI/AI/NIAID NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Ann Surg. Oct 1;276(4):673-683. doi: 10./SLA.. Epub Jul 19.I SomaScan 07/22/ Grams ME, et al. Development and Validation of Prediction Models of Adverse Kidney Outcomes in the Population With and Without Diabetes Diabetes Care 45 9 - https://www.doi.org/10./dc22- 35,856,507 Albuminuria *Diabetes Mellitus/epidemiology Glomerular Filtration Rate Humans Kidney *Renal Insufficiency *Renal Insufficiency, Chronic/epidemiology OBJECTIVE: To predict adverse kidney outcomes for use in optimizing medical management and clinical trial design. RESEARCH DESIGN AND METHODS: In this meta-analysis of individual participant data, 43 cohorts (N = 1,621,817) from research studies, electronic medical records, and clinical trials with global representation were separated into development and validation cohorts. Models were developed and validated within strata of diabetes mellitus (presence or absence) and estimated glomerular filtration rate (eGFR; >/=60 or /=40% decline in eGFR or kidney failure (i.e., receipt of kidney replacement therapy) over 2-3 years. RESULTS: There were 17,399 and 24,591 events in development and validation cohorts, respectively. Models predicting >/=40% eGFR decline or kidney failure incorporated age, sex, eGFR, albuminuria, systolic blood pressure, antihypertensive medication use, history of heart failure, coronary heart disease, atrial fibrillation, smoking status, and BMI, and, in those with diabetes, hemoglobin A1c, insulin use, and oral diabetes medication use. The median C-statistic was 0.774 (interquartile range [IQR] = 0.753, 0.782) in the diabetes and higher-eGFR validation cohorts; 0.769 (IQR = 0.758, 0.808) in the diabetes and lower-eGFR validation cohorts; 0.740 (IQR = 0.717, 0.763) in the no diabetes and higher-eGFR validation cohorts; and 0.750 (IQR = 0.731, 0.785) in the no diabetes and lower-eGFR validation cohorts. Incorporating the previous 2-year eGFR slope minimally improved model performance, and then only in the higher-eGFR cohorts. CONCLUSIONS: Novel prediction equations for a decline of >/=40% in eGFR can be applied successfully for use in the general population in persons with and without diabetes with higher or lower eGFR. Grams, Morgan E Brunskill, Nigel J Ballew, Shoshana H Sang, Yingying Coresh, Josef Matsushita, Kunihiro Surapaneni, Aditya Bell, Samira Carrero, Juan J Chodick, Gabriel Evans, Marie Heerspink, Hiddo J L Inker, Lesley A Iseki, Kunitoshi Kalra, Philip A Kirchner, H Lester Lee, Brian J Levin, Adeera Major, Rupert W Medcalf, James Nadkarni, Girish N Naimark, David M J Ricardo, Ana C Sawhney, Simon Sood, Manish M Staplin, Natalie Stempniewicz, Nikita Stengel, Benedicte Sumida, Keiichi Traynor, Jamie P van den Brand, Jan Wen, Chi-Pang Woodward, Mark Yang, Jae Won Wang, Angela Yee-Moon Tangri, Navdeep Chalmers, John Hsu, Chi-Yuan Anderson, Amanda Rao, Panduranga Feldman, Harold Chang, Alex R Ho, Kevin Green, Jamie Siddiqui, Moneeza Palmer, Colin Shalev, Varda Metzger, Marie Flamant, Martin Houillier, Pascal Haymann, Jean-Philippe Cuddeback, John Ciemins, Elizabeth Kovesdy, Csaba P Trevisan, Marco Elinder, Carl Gustaf Wettermark, Bjorn Kalra, Philip Chinnadurai, Rajkumar Tollitt, James Green, Darren Gansevoort, Ron T Gutierrez, Orlando Konta, Tsuneo Kottgen, Anna Levey, Andrew S Polkinghorne, Kevan Schaffner, Elke Zhang, Luxia Chen, Jingsha eng R01 DK/DK/NIDDK NIH HHS/ Meta-Analysis Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Diabetes Care. Sep 1;45(9):-. doi: 10./dc22-.I SomaScan 07/21/ Luo P, et al. Exploring the genetic relationship between deep vein thrombosis and plasma protein: a new research idea Expert Rev Hematol 15 9 867-873 https://www.doi.org/10./.. 35,857,435 Blood Proteins/genetics Chromogranins Complement Factor B Humans Mendelian Randomization Analysis Proteome *Venous Thrombosis/genetics Deep venous thrombosis (DVT) causality genetic correlation genetics plasma protein BACKGROUND: The aim of this article is to scan and analyze the genetic correlation between plasma proteome and deep venous thrombosis (DVT), and to explore the correlation between plasma protein and DVT. RESEARCH DESIGN AND METHODS: GWAS data of DVT and plasma proteins were analyzed with linkage disequilibrium scores, and plasma proteins that were genetically associated with DVT were screened out. To ascertain the causal link between potential plasma proteins and DVT, a Mendelian randomized (MR) study was used. This study used STRING to examine the pathogenesis of DVT in connection with the gene encoding plasma protein. RESULTS: Several suggestive plasma proteins were detected for DVT, such as Complement factor B (P value=0.), Chromogranin-A (P value=0.). Through MR analysis, we found that there was a significant positive causal relationship between Chromogranin-A (exposure) and DVT(outcome) (beta=-0., P89%), with a sensitivity of 48% for RA classification. An 8-analyte model provided superior sensitivity (69%), with comparable specificity relative to ReA (>82%). CONCLUSION: Our findings demonstrate that imminent RA diagnosis could be classified with high specificity, relative to healthy controls and ReA cases, using a panel of cytokines measured in serum samples collected within 6 months before actual diagnosis. Loza, Matthew J Nagpal, Sunil Cole, Suzanne Laird, Renee M Alcala, Ashley Rao, Navin L Riddle, Mark S Porter, Chad K eng Research Support, Non-U.S. Gov't Arthritis Rheumatol. Nov;74(11):-. doi: 10./art.. Epub Oct 7.I SomaScan 06/08/ Nocera AL, et al. Cystatin SN is a potent upstream initiator of epithelial-derived type 2 inflammation in chronic rhinosinusitis J Allergy Clin Immunol 150 4 872-881 https://www.doi.org/10./j.jaci..04.034 35,660,375 Allergens Animals Chronic Disease Cysteine Proteinase Inhibitors Cytokines Inflammation Mice *Nasal Polyps/pathology Peptide Hydrolases Proteomics *Rhinitis/metabolism *Salivary Cystatins/genetics/metabolism *Sinusitis/pathology Epithelium P-glycoprotein cystatin SA cystatin SN exome posttranslational modification sinonasal mucus transcriptome from the MEEI Curing Kids Fund, Cook Medical, Medtronics has consultant arrangements with Olympus, Medtronics, 3D Matrix, Third Wave Therapeutics, Bear-ENT, and Karl Storz has provided expert testimony on ear, nose, and throat-related cases has a patent for P-gp and cystatin inhibition for chronic rhinosinusitis and receives royalties from this patent and has stock and/or stock options in Interscope, Inquis Medical, and Diceros Therapeutics. The rest of the authors declare that they have no relevant conflicts of interest. BACKGROUND: Cystatin SN (CST1) and cystatin SA (CST2) are cysteine protease inhibitors that protect against allergen, viral, and bacterial proteases. Cystatins are overexpressed in the setting of allergic rhinitis and chronic rhinosinusitis with nasal polyps (CRSwNP); however, their role in promoting type 2 inflammation remains poorly characterized. OBJECTIVE: The purpose of this study was to use integrated poly-omics and a murine exposure model to explore the link between cystatin overexpression in CRSwNP and type 2 inflammation. METHODS: In this institutional review board- and institutional animal care and use committee-approved study, we compared tissue, exosome, and mucus CST1 and CST2 between CRSwNP and controls (n = 10 per group) by using matched whole exome sequencing, transcriptomic, proteomic, posttranslational modification, histologic, functional, and bioinformatic analyses. C57/BL6 mice were dosed with 3.9 mug/mL of CST1 or PBS intranasally for 5 to 18 days in the presence or absence of epithelial ABCB1a knockdown. Inflammatory cytokines were quantified by using Quansys multiplex assays or ELISAs. RESULTS: Of the proteins quantified, CST1 and CST2 were among the most overexpressed protease inhibitors in tissue, exosome, and mucus samples; they were localized to the epithelial layer. Multiple posttranslational modifications were identified in the polyp tissue. Exosomal CST1 and CST2 were strongly and significantly correlated with eosinophils and Lund-Mackay scores. Murine type 2 cytokine secretion and T(H)2 cell infiltration increased in a time-dependent manner following CST1 exposure and was abrogated by epithelial knockdown of ABCB1a, a regulator of epithelial cytokine secretion. CONCLUSION: CST1 is a potent upstream initiator of epithelial-derived type 2 inflammation in CRSwNP. Therapeutic strategies targeting CST activity and its associated posttranslational modifications deserve further interrogation. Nocera, Angela L Mueller, Sarina K Workman, Alan D Wu, Dawei McDonnell, Kristen Sadow, Peter M Amiji, Mansoor M Bleier, Benjamin S eng P01 CA/CA/NCI NIH HHS/ R01 NS/NS/NINDS NIH HHS/ Research Support, N.I.H., Extramural J Allergy Clin Immunol. Oct;150(4):872-881. doi: 10./j.jaci..04.034. Epub May 31.I SomaScan 06/07/ Ostling J, et al. A novel non-invasive method allowing for discovery of pathologically relevant proteins from small airways Clin Proteomics 19 1 20 https://www.doi.org/10./s-022--y 35,668,386 Asthma Biomarker Breath Exhaled air Non-invasive Non-volatiles Precision medicine Proteomics Small airways of the PExA method, and boardmember and chairholder of PExA AB. Emilia Viklund is reporting a minor chairhold in PExA AB. Dr Ostling reports personal fees from PExA AB during the conduct of the study and Employed by PExA AB while writing the manuscript but not during the planning and completion of the study. BACKGROUND: There is a lack of early and precise biomarkers for personalized respiratory medicine. Breath contains an aerosol of droplet particles, which are formed from the epithelial lining fluid when the small airways close and re-open during inhalation succeeding a full expiration. These particles can be collected by impaction using the PExA((R)) method (Particles in Exhaled Air), and are derived from an area of high clinical interest previously difficult to access, making them a potential source of biomarkers reflecting pathological processes in the small airways. RESEARCH QUESTION: Our aim was to investigate if PExA method is useful for discovery of biomarkers that reflect pathology of small airways. METHODS AND ANALYSIS: Ten healthy controls and 20 subjects with asthma, of whom 10 with small airway involvement as indicated by a high lung clearance index (LCI >/= 2.9 z-score), were examined in a cross-sectional design, using the PExA instrument. The samples were analysed with the SOMAscan proteomics platform (SomaLogic Inc.). RESULTS: Two hundred-seven proteins were detected in up to 80% of the samples. Nine proteins showed differential abundance in subjects with asthma and high LCI as compared to healthy controls. Two of these were less abundant (ALDOA4, C4), and seven more abundant (FIGF, SERPINA1, CD93, CCL18, F10, IgM, IL1RAP). sRAGE levels were lower in ex-smokers (n = 14) than in never smokers (n = 16). Gene Ontology (GO) annotation database analyses revealed that the PEx proteome is enriched in extracellular proteins associated with extracellular exosome-vesicles and innate immunity. CONCLUSION: The applied analytical method was reproducible and allowed identification of pathologically interesting proteins in PEx samples from asthmatic subjects with high LCI. The results suggest that PEx based proteomics is a novel and promising approach to study respiratory diseases with small airway involvement. Ostling, Jorgen Van Geest, Marleen Olsson, Henric K Dahlen, Sven-Erik Viklund, Emilia Gustafsson, Per M Mirgorodskaya, Ekaterina Olin, Anna-Carin eng England Clin Proteomics. Jun 6;19(1):20. doi: 10./s-022--y.I SomaScan 06/07/ Oskarsson GR, et al. Genetic architecture of band neutrophil fraction in Iceland Commun Biol 5 1 525 https://www.doi.org/10./s-022--1 35,650,273 Genome-Wide Association Study Granulocytes/metabolism Humans Iceland Neutrophils/metabolism *Pelger-Huet Anomaly/genetics The characteristic lobulated nuclear morphology of granulocytes is partially determined by composition of nuclear envelope proteins. Abnormal nuclear morphology is primarily observed as an increased number of hypolobulated immature neutrophils, called band cells, during infection or in rare envelopathies like Pelger-Huet anomaly. To search for sequence variants affecting nuclear morphology of granulocytes, we performed a genome-wide association study using band neutrophil fraction from 88,101 Icelanders. We describe 13 sequence variants affecting band neutrophil fraction at nine loci. Five of the variants are at the Lamin B receptor (LBR) locus, encoding an inner nuclear membrane protein. Mutations in LBR are linked to Pelger-Huet anomaly. In addition, we identify cosegregation of a rare stop-gain sequence variant in LBR and Pelger Huet anomaly in an Icelandic eight generation pedigree, initially reported in . Two of the other loci include genes which, like LBR, play a role in the nuclear membrane function and integrity. These GWAS results highlight the role proteins of the inner nuclear membrane have as important for neutrophil nuclear morphology. Oskarsson, Gudjon R Magnusson, Magnus K Oddsson, Asmundur Jensson, Brynjar O Fridriksdottir, Run Arnadottir, Gudny A Katrinardottir, Hildigunnur Rognvaldsson, Solvi Halldorsson, Gisli H Sveinbjornsson, Gardar Ivarsdottir, Erna V Stefansdottir, Lilja Ferkingstad, Egil Norland, Kristjan Tragante, Vinicius Saemundsdottir, Jona Jonasdottir, Aslaug Jonasdottir, Adalbjorg Sigurjonsdottir, Svanhvit Petursdottir, Karen O Davidsson, Olafur B Rafnar, Thorunn Holm, Hilma Olafsson, Isleifur Onundarson, Pall T Vidarsson, Brynjar Sigurdardottir, Olof Masson, Gisli Gudbjartsson, Daniel F Jonsdottir, Ingileif Norddahl, Gudmundur L Thorsteinsdottir, Unnur Sulem, Patrick Stefansson, Kari eng England Commun Biol. Jun 1;5(1):525. doi: 10./s-022--1.I SomaScan 06/02/ Komarova N, et al. Aptamers Targeting Cardiac Biomarkers as an Analytical Tool for the Diagnostics of Cardiovascular Diseases: A Review Biomedicines 10 5 https://www.doi.org/10./biomedicines 35,625,822 aptamer biosensor cardiac biomarkers cardiovascular disease detection diagnostics The detection of cardiac biomarkers is used for diagnostics, prognostics, and the risk assessment of cardiovascular diseases. The analysis of cardiac biomarkers is routinely performed with high-sensitivity immunological assays. Aptamers offer an attractive alternative to antibodies for analytical applications but, to date, are not widely practically implemented in diagnostics and medicinal research. This review summarizes the information on the most common cardiac biomarkers and the current state of aptamer research regarding these biomarkers. Aptamers as an analytical tool are well established for troponin I, troponin T, myoglobin, and C-reactive protein. For the rest of the considered cardiac biomarkers, the isolation of novel aptamers or more detailed characterization of the known aptamers are required. More attention should be addressed to the development of dual-aptamer sandwich detection assays and to the studies of aptamer sensing in alternative biological fluids. The universalization of aptamer-based biomarker detection platforms and the integration of aptamer-based sensing to clinical studies are demanded for the practical implementation of aptamers to routine diagnostics. Nevertheless, the wide usage of aptamers for the diagnostics of cardiovascular diseases is promising for the future, with respect to both point-of-care and laboratory testing. Komarova, Natalia Panova, Olga Titov, Alexey Kuznetsov, Alexander eng 21-79-/Russian Science Foundation/ Review Switzerland Biomedicines. May 6;10(5):. doi: 10./biomedicines.I SomaScan 05/29/ Kobayashi H, et al. Results of untargeted analysis using the SOMAscan proteomics platform indicates novel associations of circulating proteins with risk of progression to kidney failure in diabetes Kidney Int 102 2 370-381 https://www.doi.org/10./j.kint..04.022 35,618,095 Biomarkers/metabolism *Diabetes Mellitus, Type 2/complications *Diabetic Nephropathies/complications/etiology Disease Progression Endostatins Humans Lectins, C-Type Proteomics/methods *Renal Insufficiency circulating biomarker diabetes diabetic kidney disease end-stage kidney disease proteomics analysis patent for predicting risk of ESRD This study applies a large proteomics panel to search for new circulating biomarkers associated with progression to kidney failure in individuals with diabetic kidney disease. Four independent cohorts encompassing 754 individuals with type 1 and type 2 diabetes and early and late diabetic kidney disease were followed to ascertain progression to kidney failure. During ten years of follow-up, 227 of 754 individuals progressed to kidney failure. Using the SOMAscan proteomics platform, we measured baseline concentration of circulating proteins. In our previous publications, we analyzed 334 of these proteins that were members of specific candidate pathways involved in diabetic kidney disease and found 35 proteins strongly associated with risk of progression to kidney failure. Here, we examined the remaining 795 proteins using an untargeted approach. Of these remaining proteins, 11 were significantly associated with progression to kidney failure. Biological processes previously reported for these proteins were related to neuron development (DLL1, MATN2, NRX1B, KLK8, RTN4R and ROR1) and were implicated in the development of kidney fibrosis (LAYN, DLL1, MAPK11, MATN2, endostatin, and ROR1) in cellular and animal studies. Specific mechanisms that underlie involvement of these proteins in progression of diabetic kidney disease must be further investigated to assess their value as targets for kidney-protective therapies. Using multivariable LASSO regression analysis, five proteins (LAYN, ESAM, DLL1, MAPK11 and endostatin) were found independently associated with risk of progression to kidney failure. Thus, our study identified proteins that may be considered as new candidate prognostic biomarkers to predict risk of progression to kidney failure in diabetic kidney disease. Furthermore, three of these proteins (DLL1, ESAM, and MAPK11) were selected as candidate biomarkers when all SOMAscan results were evaluated. Kobayashi, Hiroki Looker, Helen C Satake, Eiichiro Saulnier, Pierre Jean Md Dom, Zaipul I O'Neil, Kristina Ihara, Katsuhito Krolewski, Bozena Galecki, Andrzej T Niewczas, Monika A Wilson, Jonathan M Doria, Alessandro Duffin, Kevin L Nelson, Robert G Krolewski, Andrzej S eng ZIA DK/ImNIH/Intramural NIH HHS/ R01 DK/DK/NIDDK NIH HHS/ P30 DK/DK/NIDDK NIH HHS/ R01 DK/DK/NIDDK NIH HHS/ R01 DK/DK/NIDDK NIH HHS/ Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Kidney Int. Aug;102(2):370-381. doi: 10./j.kint..04.022. Epub May 23.I SomaScan 05/27/ Matsuno H, et al. Association between vascular endothelial growth factor-mediated blood-brain barrier dysfunction and stress-induced depression Mol Psychiatry 27 9 - https://www.doi.org/10./s-022--3 35,618,888 Animals Mice Blood-Brain Barrier/metabolism Vascular Endothelial Growth Factor A/metabolism Endothelial Cells/metabolism *Depressive Disorder, Major/metabolism Depression *Brain Diseases/pathology Mice, Inbred BALB C Capillary Permeability/physiology Several lines of evidence suggest that stress induces the neurovascular dysfunction associated with increased blood-brain barrier (BBB) permeability, which could be an important pathology linking stress and psychiatric disorders, including major depressive disorder (MDD). However, the detailed mechanism resulting in BBB dysfunction associated in the pathophysiology of MDD still remains unclear. Herein, we demonstrate the role of vascular endothelial growth factor (VEGF), a key mediator of vascular angiogenesis and BBB permeability, in stress-induced BBB dysfunction and depressive-like behavior development. We implemented an animal model of depression, chronic restraint stress (RS) in BALB/c mice, and found that the BBB permeability was significantly increased in chronically stressed mice. Immunohistochemical and electron microscopic observations revealed that increased BBB permeability was associated with both paracellular and transcellular barrier alterations in the brain endothelial cells. Pharmacological inhibition of VEGF receptor 2 (VEGFR2) using a specific monoclonal antibody (DC101) prevented chronic RS-induced BBB permeability and anhedonic behavior. Considered together, these results indicate that VEGF/VEGFR2 plays a crucial role in the pathogenesis of depression by increasing the BBB permeability, and suggest that VEGFR2 inhibition could be a potential therapeutic strategy for the MDD subtype associated with BBB dysfunction. Matsuno, Hitomi Tsuchimine, Shoko O'Hashi, Kazunori Sakai, Kazuhisa Hattori, Kotaro Hidese, Shinsuke Nakajima, Shingo Chiba, Shuichi Yoshimura, Aya Fukuzato, Noriko Kando, Mayumi Tatsumi, Megumi Ogawa, Shintaro Ichinohe, Noritaka Kunugi, Hiroshi Sohya, Kazuhiro eng 17K/MEXT | Japan Society for the Promotion of Science (JSPS)/ 20K/MEXT | Japan Society for the Promotion of Science (JSPS)/ 19K/MEXT | Japan Society for the Promotion of Science (JSPS)/ 16KT/MEXT | Japan Society for the Promotion of Science (JSPS)/ 19akh/Japan Agency for Medical Research and Development (AMED)/ 19akh/Japan Agency for Medical Research and Development (AMED)/ England Mol Psychiatry. Sep;27(9):-. doi: 10./s-022--3. Epub May 26.I SomaScan 05/27/ Haslam DE, et al. Stability and reproducibility of proteomic profiles in epidemiological studies: comparing the Olink and SOMAscan platforms Proteomics 22 13 e https://www.doi.org/10./pmic. 35,598,103 Epidemiologic Studies Follow-Up Studies Humans *Proteomics Reproducibility of Results *Specimen Handling Aptamers biomarkers epidemiology studies laboratory methods and tools multiplexing systems biology Limited data exist on the performance of high-throughput proteomics profiling in epidemiological settings, including the impact of specimen collection and within-person variability over time. Thus, the Olink (972 proteins) and SOMAscan7Kv4.1 ( proteoforms of proteins) assays were utilized to measure protein concentrations in archived plasma samples from the Nurses' Health Studies and Health Professionals Follow-Up Study. Spearman's correlation coefficients (r) and intraclass correlation coefficients (ICCs) were used to assess agreement between (1) 42 triplicate samples processed immediately, 24-h or 48-h after blood collection from 14 participants; and (2) 80 plasma samples from 40 participants collected 1-year apart. When comparing samples processed immediately, 24-h, and 48-h later, 55% of assays had an ICC/r >/= 0.75 and 87% had an ICC/r >/= 0.40 in Olink compared to 44% with an ICC/r >/= 0.75 and 72% with an ICC/r >/= 0.40 in SOMAscan7K. For both platforms, >90% of the assays were stable (ICC/r >/= 0.40) in samples collected 1-year apart. Among 817 proteins measured with both platforms, Spearman's correlations were high (r > 0.75) for 14.7% and poor (r analytes in the media conditioned by NOK cells and HNSCC cells +/- PI3K inhibitor. These results demonstrated that NOK cells release abundant levels of ligands that activate epidermal growth factor receptor (EGFR) and fibroblast growth factor receptor (FGFR), two receptor tyrosine kinases with oncogenic activity. Inhibition of EGFR, but not FGFR, blunted PI3K inhibitor resistance and CSC phenotypes induced by NOK cells. Our results demonstrate that precancerous keratinocytes can directly support neighboring HNSCC by activating EGFR. Importantly, PI3K inhibitor sensitivity was not necessarily a cancer cell-intrinsic property, and the tumor microenvironment impacts therapeutic response and supports CSCs. Additionally, combined inhibition of EGFR with PI3K inhibitor diminished EGFR activation induced by PI3K inhibitor and potently inhibited cancer cell proliferation and CSC maintenance." Nguyen, Khoa A Keith, Madison J Keysar, Stephen B Hall, Spencer C Bimali, Anamol Jimeno, Antonio Wang, Xiao-Jing Young, Christian D eng P50 CA/CA/NCI NIH HHS/ R01 DE/DE/NIDCR NIH HHS/ I01 BX/BX/BLRD VA/ IK6 BX/BX/BLRD VA/ P30 CA/CA/NCI NIH HHS/ R01 DE/DE/NIDCR NIH HHS/ R01 DE/DE/NIDCR NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Mol Carcinog. Jul;61(7):664-676. doi: 10./mc.. Epub Apr 13.I SomaScan 04/14/ Aid M, et al. Ad26.COV2.S prevents upregulation of SARS-CoV-2 induced pathways of inflammation and thrombosis in hamsters and rhesus macaques PLoS Pathog 18 4 e https://www.doi.org/10./journal.ppat. 35,395,058 Ad26COVS1 Animals Antibodies, Neutralizing *covid-19 COVID-19 Vaccines Cricetinae Humans Inflammation Macaca mulatta SARS-CoV-2 Spike Glycoprotein, Coronavirus *Thrombosis Up-Regulation Syrian golden hamsters exhibit features of severe disease after SARS-CoV-2 WA1/ challenge and are therefore useful models of COVID-19 pathogenesis and prevention with vaccines. Recent studies have shown that SARS-CoV-2 infection stimulates type I interferon, myeloid, and inflammatory signatures similar to human disease and that weight loss can be prevented with vaccines. However, the impact of vaccination on transcriptional programs associated with COVID-19 pathogenesis and protective adaptive immune responses is unknown. Here we show that SARS-CoV-2 WA1/ challenge in hamsters stimulates myeloid and inflammatory programs as well as signatures of complement and thrombosis associated with human COVID-19. Notably, immunization with Ad26.COV2.S, an adenovirus serotype 26 vector (Ad26)-based vaccine expressing a stabilized SARS-CoV-2 spike protein, prevents the upregulation of these pathways, such that the mRNA expression profiles of vaccinated hamsters are comparable to uninfected animals. Using proteomics profiling, we validated these findings in rhesus macaques challenged with SARS-CoV-2 WA1/ or SARS-CoV-2 B.1.351. Finally, we show that Ad26.COV2.S vaccination induces T and B cell signatures that correlate with binding and neutralizing antibody responses weeks following vaccination. These data provide insights into the molecular mechanisms of Ad26.COV2.S protection against severe COVID-19 in animal models. Aid, Malika Vidal, Samuel J Piedra-Mora, Cesar Ducat, Sarah Chan, Chi N Bondoc, Stephen Colarusso, Alessandro Starke, Carly E Nekorchuk, Michael Busman-Sahay, Kathleen Estes, Jacob D Martinot, Amanda J Barouch, Dan H eng P51 OD/OD/NIH HHS/ Research Support, Non-U.S. Gov't PLoS Pathog. Apr 8;18(4):e. doi: 10./journal.ppat.. eCollection Apr.I SomaScan 04/09/ Harbaum L, et al. Mining the Plasma Proteome for Insights into the Molecular Pathology of Pulmonary Arterial Hypertension Am J Respir Crit Care Med 205 12 - https://www.doi.org/10./rccm.-OC 35,394,406 Blood Proteins/genetics Familial Primary Pulmonary Hypertension Humans *Hypertension, Pulmonary Netrins Pathology, Molecular Proteome *Pulmonary Arterial Hypertension Thrombospondins Mendelian randomization case-control studies genome protein quantitative trait loci Rationale: Pulmonary arterial hypertension (PAH) is characterized by structural remodeling of pulmonary arteries and arterioles. Underlying biological processes are likely reflected in a perturbation of circulating proteins. Objectives: To quantify and analyze the plasma proteome of patients with PAH using inherited genetic variation to inform on underlying molecular drivers. Methods: An aptamer-based assay was used to measure plasma proteins in 357 patients with idiopathic or heritable PAH, 103 healthy volunteers, and 23 relatives of patients with PAH. In discovery and replication subgroups, the plasma proteomes of PAH and healthy individuals were compared, and the relationship to transplantation-free survival in PAH was determined. To examine causal relationships to PAH, protein quantitative trait loci (pQTL) that influenced protein levels in the patient population were used as instruments for Mendelian randomization (MR) analysis. Measurements and Main Results: From 4,152 annotated plasma proteins, levels of 208 differed between patients with PAH and healthy subjects, and 49 predicted long-term survival. MR based on cis-pQTL located in proximity to the encoding gene for proteins that were prognostic and distinguished PAH from health estimated an adverse effect for higher levels of netrin-4 (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.16-2.08) and a protective effect for higher levels of thrombospondin-2 (OR, 0.83; 95% CI, 0.74-0.94) on PAH. Both proteins tracked the development of PAH in previously healthy relatives and changes in thrombospondin-2 associated with pulmonary arterial pressure at disease onset. Conclusions: Integrated analysis of the plasma proteome and genome implicates two secreted matrix-binding proteins, netrin-4 and thrombospondin-2, in the pathobiology of PAH. Harbaum, Lars Rhodes, Christopher J Wharton, John Lawrie, Allan Karnes, Jason H Desai, Ankit A Nichols, William C Humbert, Marc Montani, David Girerd, Barbara Sitbon, Olivier Boehm, Mario Novoyatleva, Tatyana Schermuly, Ralph T Ghofrani, H Ardeschir Toshner, Mark Kiely, David G Howard, Luke S Swietlik, Emilia M Graf, Stefan Pietzner, Maik Morrell, Nicholas W Wilkins, Martin R eng R01HL/NIH/NHLBI/ R01 HL/HL/NHLBI NIH HHS/ FS/13/48//BHF_/British Heart Foundation/United Kingdom FS/15/59//BHF_/British Heart Foundation/United Kingdom R24 HL/HL/NHLBI NIH HHS/ SP/12/12//BHF_/British Heart Foundation/United Kingdom K01HL/NIH/NHLBI/ R01 HL/HL/NHLBI NIH HHS/ RE/18/4//BHF_/British Heart Foundation/United Kingdom R01 HL/HL/NHLBI NIH HHS/ MR/K/1/MRC_/Medical Research Council/United Kingdom DH_/Department of Health/United Kingdom FS/18/52//BHF_/British Heart Foundation/United Kingdom Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Am J Respir Crit Care Med. Jun 15;205(12):-. doi: 10./rccm.-OC.I SomaScan 04/09/ Dillon ST, et al. Patterns and Persistence of Perioperative Plasma and Cerebrospinal Fluid Neuroinflammatory Protein Biomarkers After Elective Orthopedic Surgery Using SOMAscan Anesth Analg epub ahead of print https://www.doi.org/10./ANE. 35,389,379 BACKGROUND: The neuroinflammatory response to surgery can be characterized by peripheral acute plasma protein changes in blood, but corresponding, persisting alterations in cerebrospinal fluid (CSF) proteins remain mostly unknown. Using the SOMAscan assay, we define acute and longer-term proteome changes associated with surgery in plasma and CSF. We hypothesized that biological pathways identified by these proteins would be in the categories of neuroinflammation and neuronal function and define neuroinflammatory proteome changes associated with surgery in older patients. METHODS: SOMAscan analyzed proteins in blood plasma (n = 14) and CSF (n = 15) samples from older patients enrolled in the Role of Inflammation after Surgery for Elders (RISE) study undergoing elective hip and knee replacement surgery with spinal anesthesia. Systems biology analysis identified biological pathways enriched among the surgery-associated differentially expressed proteins in plasma and CSF. RESULTS: Comparison of postoperative day 1 (POD1) to preoperative (PREOP) plasma protein levels identified 343 proteins with postsurgical changes (P 1.2). Comparing postoperative 1-month (PO1MO) plasma and CSF with PREOP identified 67 proteins in plasma and 79 proteins in CSF with altered levels (P 1.2). In plasma, 21 proteins, primarily linked to immune response and inflammation, were similarly changed at POD1 and PO1MO. Comparison of plasma to CSF at PO1MO identified 8 shared proteins. Comparison of plasma at POD1 to CSF at PO1MO identified a larger number, 15 proteins in common, most of which are regulated by interleukin-6 (IL-6) or transforming growth factor beta-1 (TGFB1) and linked to the inflammatory response. Of the 79 CSF PO1MO-specific proteins, many are involved in neuronal function and neuroinflammation. CONCLUSIONS: SOMAscan can characterize both short- and long-term surgery-induced protein alterations in plasma and CSF. Acute plasma protein changes at POD1 parallel changes in PO1MO CSF and suggest 15 potential biomarkers for longer-term neuroinflammation that warrant further investigation. Dillon, Simon T Otu, Hasan H Ngo, Long H Fong, Tamara G Vasunilashorn, Sarinnapha M Xie, Zhongcong Kunze, Lisa J Vlassakov, Kamen V Abdeen, Ayesha Lange, Jeffrey K Earp, Brandon E Cooper, Zara R Schmitt, Eva M Arnold, Steven E Hshieh, Tammy T Jones, Richard N Inouye, Sharon K Marcantonio, Edward R Libermann, Towia A eng R01 AG/AG/NIA NIH HHS/ R03 AG/AG/NIA NIH HHS/ K24 AG/AG/NIA NIH HHS/ K01 AG/AG/NIA NIH HHS/ P01 AG/AG/NIA NIH HHS/ R21 AG/AG/NIA NIH HHS/ R24 AG/AG/NIA NIH HHS/ Anesth Analg. Apr 7:10./ANE.. doi: 10./ANE..I SomaScan 04/08/ Williams SA, et al. A proteomic surrogate for cardiovascular outcomes that is sensitive to multiple mechanisms of change in risk Sci Transl Med 14 639 eabj https://www.doi.org/10./scitranslmed.abj 35,385,337 Biomarkers *Cardiovascular Diseases *Heart Failure/drug therapy Humans *Myocardial Infarction/drug therapy Proteomics *Stroke/complications A reliable, individualized, and dynamic surrogate of cardiovascular risk, synoptic for key biologic mechanisms, could shorten the path for drug development, enhance drug cost-effectiveness and improve patient outcomes. We used highly multiplexed proteomics to address these objectives, measuring about proteins in each of 32,130 archived plasma samples from 22,849 participants in nine clinical studies. We used machine learning to derive a 27-protein model predicting 4-year likelihood of myocardial infarction, stroke, heart failure, or death. The 27 proteins encompassed 10 biologic systems, and 12 were associated with relevant causal genetic traits. We independently validated results in 11,609 participants. Compared to a clinical model, the ratio of observed events in quintile 5 to quintile 1 was 6.7 for proteins versus 2.9 for the clinical model, AUCs (95% CI) were 0.73 (0.72 to 0.74) versus 0.64 (0.62 to 0.65), c-statistics were 0.71 (0.69 to 0.72) versus 0.62 (0.60 to 0.63), and the net reclassification index was +0.43. Adding the clinical model to the proteins only improved discrimination metrics by 0.01 to 0.02. Event rates in four predefined protein risk categories were 5.6, 11.2, 20.0, and 43.4% within 4 years; median time to event was 1.71 years. Protein predictions were directionally concordant with changed outcomes. Adverse risks were predicted for aging, approaching an event, anthracycline chemotherapy, diabetes, smoking, rheumatoid arthritis, cancer history, cardiovascular disease, high systolic blood pressure, and lipids. Reduced risks were predicted for weight loss and exenatide. The 27-protein model has potential as a universal" surrogate end point for cardiovascular risk." Williams, Stephen A Ostroff, Rachel Hinterberg, Michael A Coresh, Josef Ballantyne, Christie M Matsushita, Kunihiro Mueller, Christian E Walter, Joan Jonasson, Christian Holman, Rury R Shah, Svati H Sattar, Naveed Taylor, Roy Lean, Michael E Kato, Shintaro Shimokawa, Hiroaki Sakata, Yasuhiko Nochioka, Kotaro Parikh, Chirag R Coca, Steven G Omland, Torbjorn Chadwick, Jessica Astling, David Hagar, Yolanda Kureshi, Natasha Loupy, Kelsey Paterson, Clare Primus, Jeremy Simpson, Missy Trujillo, Nelson P Ganz, Peter eng R01 HL/HL/NHLBI NIH HHS/ HHSNI/HL/NHLBI NIH HHS/ HHSNI/HL/NHLBI NIH HHS/ HHSNI/HL/NHLBI NIH HHS/ HHSNI/HL/NHLBI NIH HHS/ HHSNI/HL/NHLBI NIH HHS/ R01 HL/HL/NHLBI NIH HHS/ R01 HL/HL/NHLBI NIH HHS/ U01 HG/HG/NHGRI NIH HHS/ R01 HL/HL/NHLBI NIH HHS/ U01 DK/DK/NIDDK NIH HHS/ R01 HL/HL/NHLBI NIH HHS/ U01 DK/DK/NIDDK NIH HHS/ R01 AG/AG/NIA NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Sci Transl Med. Apr 6;14(639):eabj. doi: 10./scitranslmed.abj. Epub Apr 6.I SomaScan 04/07/ Hardy-Sosa A, et al. Diagnostic Accuracy of Blood-Based Biomarker Panels: A Systematic Review Front Aging Neurosci 14 https://www.doi.org/10./fnagi.. 35,360,215 Alzheimer's disease (AD) biomarker panel blood-based biomarker diagnosis preclinical AD commercial or financial relationships that could be construed as a potential conflict of interest. BACKGROUND: Because of high prevalence of Alzheimer's disease (AD) in low- and middle-income countries (LMICs), there is an urgent need for inexpensive and minimally invasive diagnostic tests to detect biomarkers in the earliest and asymptomatic stages of the disease. Blood-based biomarkers are predicted to have the most impact for use as a screening tool and predict the onset of AD, especially in LMICs. Furthermore, it has been suggested that panels of markers may perform better than single protein candidates. METHODS: Medline/Pubmed was searched to identify current relevant studies published from January to December . We included all full-text articles examining blood-based biomarkers as a set of protein markers or panels to aid in AD's early diagnosis, prognosis, and characterization. RESULTS: Seventy-six articles met the inclusion criteria for systematic review. Majority of the studies reported plasma and serum as the main source for biomarker determination in blood. Protein-based biomarker panels were reported to aid in AD diagnosis and prognosis with better accuracy than individual biomarkers. Conventional (amyloid-beta and tau) and neuroinflammatory biomarkers, such as amyloid beta-42, amyloid beta-40, total tau, phosphorylated tau-181, and other tau isoforms, were the most represented. We found the combination of amyloid beta-42/amyloid beta-40 ratio and APOEepsilon4 status to be most represented with high accuracy for predicting amyloid beta-positron emission tomography status. CONCLUSION: Assessment of Alzheimer's disease biomarkers in blood as a non-invasive and cost-effective alternative will potentially contribute to early diagnosis and improvement of therapeutic interventions. Given the heterogeneous nature of AD, combination of markers seems to perform better in the diagnosis and prognosis of the disease than individual biomarkers. Hardy-Sosa, Anette Leon-Arcia, Karen Llibre-Guerra, Jorge J Berlanga-Acosta, Jorge Baez, Saiyet de la C Guillen-Nieto, Gerardo Valdes-Sosa, Pedro A eng Switzerland Front Aging Neurosci. Mar 11;14:. doi: 10./fnagi... eCollection .I SomaScan 04/02/ Honey S, et al. Acceptability and experience of a personalised proteomic risk intervention for type 2 diabetes in primary care: qualitative interview study with patients and healthcare providers Prim Health Care Res Dev 23 e24 https://www.doi.org/10./S 35,361,303 *Diabetes Mellitus, Type 2/prevention & control Health Personnel Humans Primary Health Care Proteomics Qualitative Research behaviour change pre-diabetes proteomic risk assessment type 2 diabetes AIM: We explored the acceptability of a personalised proteomic risk intervention for patients at increased risk of type 2 diabetes and their healthcare providers, as well as their experience of participating in the delivery of proteomic-based risk feedback in UK primary care. BACKGROUND: Advances in proteomics now allow the provision of personalised proteomic risk reports, with the intention of achieving positive behaviour change. This technology has the potential to encourage behaviour change in people at risk of developing type 2 diabetes. METHODS: A semi-structured interview study was carried out with patients at risk of type 2 diabetes and their healthcare providers in primary care in the North of England. Participants (n = 17) and healthcare provider (n = 4) were interviewed either face to face or via . Data were analysed using thematic analysis. This qualitative study was nested within a single-arm pilot trial and undertaken in primary care. FINDINGS: The personalised proteomic risk intervention was generally acceptable and the experience was positive. The personalised nature of the report was welcomed, especially the way it provided a holistic approach to risks of organ damage and lifestyle factors. Insights were provided as to how this may change behaviour. Some participants reported difficulties in understanding the format of the presentation of risk and expressed surprise at receiving risk estimates for conditions other than type 2 diabetes. Personalised proteomic risk interventions have the potential to provide holistic and comprehensive assessments of risk factors and lifestyle factors which may lead to positive behaviour change. Honey, Stephanie Neal, Richard D Messenger, Michael Smith, Samuel G eng DH_/Department of Health/United Kingdom Research Support, Non-U.S. Gov't England Prim Health Care Res Dev. Apr 1;23:e24. doi: 10./S.I SomaScan 04/02/ Liu S, et al. Translation of aptamers toward clinical diagnosis and commercialization Biosens Bioelectron 208 https://www.doi.org/10./j.bios.. 35,364,525 *Aptamers, Nucleotide *Biosensing Techniques Point-of-Care Testing SELEX Aptamer Technique Aptamer Aptasensor Clinical diagnostic Point-of-care test Translation The dominance of antibodies in diagnostics has gradually changed following the discovery of aptamers in the early s. Aptamers offer inherent advantages over traditional antibodies, including higher specificity, higher affinity, smaller size, greater stability, ease of manufacture, and low immunogenicity, rendering them the best candidates for point-of-care testing (POCT). In the past 20 years, the research community and pharmaceutical companies have made great efforts to promote the development of aptamer technology. Macugen(R) (pegaptanib) was the first aptamer drug approved by the US Food and Drug Administration (FDA), and various aptamer-based diagnostics show great promise in preclinical research and clinical trials. In this review, we introduce recent literature, ongoing clinical trials, commercial reagents of aptamer-based diagnostics, discuss the FDA regulatory mechanisms, and highlight the prospects and challenges in translating these studies into viable clinical diagnostic tools. Liu, Shan Xu, Yixin Jiang, Xin Tan, Hong Ying, Binwu eng Review England Biosens Bioelectron. Jul 15;208:. doi: 10./j.bios... Epub Mar 16.I SomaScan 04/02/ Osawa Y, et al. Plasma Growth and Differentiation Factor 15 Predict Longitudinal Changes in Bone Parameters in Women, but Not in Men J Gerontol A Biol Sci Med Sci 77 10 - https://www.doi.org/10./gerona/glac079 35,363,860 Aged Aged, 80 and over Bone Density/physiology *Bone Diseases, Metabolic *Calcium Female Growth Differentiation Factor 15 Humans Male Parathyroid Hormone Radius/physiology Tibia/diagnostic imaging/physiology Cortical bone Growth/differentiation factor 15 Osteopenia Sex difference Trabecular bone Bone fragility can progress with aging, but biomarkers to detect emerging osteopenia have not been fully elucidated. Growth/differentiation factor 15 (GDF-15) has pleiotropic roles in a broad range of age-related conditions, but its association with osteopenia is unknown. We examined the relationship between plasma GDF-15 levels and rate of change in bone parameters over 9 years of follow-up in 596 adults in the InCHIANTI study (baseline age, 65-94 years; women, 52.4%; mean follow-up, 7.0 +/- 3.0 years). Plasma GDF-15 concentrations were measured using the 1.3k HTS SOMAscan assay. Eight bone parameters were measured in the right tibia by peripheral quantitative computed tomography; total bone density, trabecular bone density, medullary plus trabecular bone density, cortical bone density, total bone area, cortical bone area, medullary bone area, and minimum moment of inertia (mMOI). We ran sex-specific linear mixed-effect models with random intercepts and slopes adjusted for age, age-squared, education, body mass index, the rate of change in weight, smoking, sedentary behavior, cross-sectional areas of calf muscles and fat, 25-hydroxyvitamin D, parathyroid hormone, calcium, diabetes mellitus, and follow-up time. We found a significant association of baseline GDF-15 x time" in models predicting cortical bone density and the mMOI in women, suggesting that the rates of decline in these bone parameters increased with higher GDF-15 (false discovery rate /=75th percentile) was more common in people with diabetes compared with those without diabetes (32.8% vs 23.6%, p analytes per sample, offering a high-throughput alternative to traditional immunoassays in biomarker discovery. However, the specificity for distinct proteins has not been thoroughly studied in the context of CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We assessed the use of SOMAscan, an aptamer-based technology, for the quantification of eight immune activation biomarkers and cystatin C among 498 African American Study of Kidney Disease and Hypertension (AASK) participants using immunoassays as the gold standard. We evaluated correlations of serum proteins as measured by SOMAscan versus immunoassays with each other and with iothalamate-measured GFR. We then compared associations between proteins measurement with risks of incident kidney failure and all-cause mortality. RESULTS: Six biomarkers (IL-8, soluble TNF receptor superfamily member 1B [TNFRSF1B], cystatin C, soluble TNF receptor superfamily member 1A [TNFRSF1A], IL-6, and soluble urokinase-type plasminogen activator receptor [suPAR]) had non-negligible correlations (r=0.94, 0.93, 0.89, 0.85, 0.46, and 0.23, respectively) between SOMAscan and immunoassay measurements, and three (IL-10, IFN-gamma, and TNF-alpha) were uncorrelated (r=0.08, 0.07, and 0.02, respectively). Of the six biomarkers with non-negligible correlations, TNFRSF1B, cystatin C, TNFRSF1A, and suPAR were negatively correlated with measured GFR and associated with higher risk of kidney failure. IL-8, TNFRSF1B, cystatin C, TNFRSF1A, and suPAR were associated with a higher risk of mortality via both methods. On average, immunoassay measurements were more strongly associated with adverse outcomes than their SOMAscan counterparts. CONCLUSIONS: SOMAscan is an efficient and relatively reliable technique for quantifying IL-8, TNFRSF1B, cystatin C, and TNFRSF1A in CKD and detecting their potential associations with clinical outcomes. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/_02_23_CJN.mp3. Lopez-Silva, Carolina Surapaneni, Aditya Coresh, Josef Reiser, Jochen Parikh, Chirag R Obeid, Wassim Grams, Morgan E Chen, Teresa K eng U01 DK/DK/NIDDK NIH HHS/ P20 RR/RR/NCRR NIH HHS/ P30 DK/DK/NIDDK NIH HHS/ U01 DK/DK/NIDDK NIH HHS/ K08 DK/DK/NIDDK NIH HHS/ M01 RR/RR/NCRR NIH HHS/ P20 RR/RR/NCRR NIH HHS/ K24 HL/HL/NHLBI NIH HHS/ R01 DK/DK/NIDDK NIH HHS/ M01 RR/RR/NCRR NIH HHS/ UL1 RR/RR/NCRR NIH HHS/ K24 DK/DK/NIDDK NIH HHS/ M01 RR/RR/NCRR NIH HHS/ M01 RR/RR/NCRR NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Clin J Am Soc Nephrol. Mar;17(3):350-360. doi: 10./CJN.. Epub Feb 23.I SomaScan 02/25/ Schubert R, et al. Protein prediction for trait mapping in diverse populations PLoS One 17 2 e https://www.doi.org/10./journal.pone. 35,202,437 Atherosclerosis/ethnology/*genetics Female Gene Frequency *Genetic Association Studies Humans Male *Models, Genetic Pilot Projects Polymorphism, Single Nucleotide Proteins/*genetics Proteome/*genetics Quantitative Trait Loci Genetically regulated gene expression has helped elucidate the biological mechanisms underlying complex traits. Improved high-throughput technology allows similar interrogation of the genetically regulated proteome for understanding complex trait mechanisms. Here, we used the Trans-omics for Precision Medicine (TOPMed) Multi-omics pilot study, which comprises data from Multi-Ethnic Study of Atherosclerosis (MESA), to optimize genetic predictors of the plasma proteome for genetically regulated proteome-wide association studies (PWAS) in diverse populations. We built predictive models for protein abundances using data collected in TOPMed MESA, for which we have measured 1,305 proteins by a SOMAscan assay. We compared predictive models built via elastic net regression to models integrating posterior inclusion probabilities estimated by fine-mapping SNPs prior to elastic net. In order to investigate the transferability of predictive models across ancestries, we built protein prediction models in all four of the TOPMed MESA populations, African American (n = 183), Chinese (n = 71), European (n = 416), and Hispanic/Latino (n = 301), as well as in all populations combined. As expected, fine-mapping produced more significant protein prediction models, especially in African ancestries populations, potentially increasing opportunity for discovery. When we tested our TOPMed MESA models in the independent European INTERVAL study, fine-mapping improved cross-ancestries prediction for some proteins. Using GWAS summary statistics from the Population Architecture using Genomics and Epidemiology (PAGE) study, which comprises approximately 50,000 Hispanic/Latinos, African Americans, Asians, Native Hawaiians, and Native Americans, we applied S-PrediXcan to perform PWAS for 28 complex traits. The most protein-trait associations were discovered, colocalized, and replicated in large independent GWAS using proteome prediction model training populations with similar ancestries to PAGE. At current training population sample sizes, performance between baseline and fine-mapped protein prediction models in PWAS was similar, highlighting the utility of elastic net. Our predictive models in diverse populations are publicly available for use in proteome mapping methods at https://doi.org/10./zenodo.. Schubert, Ryan Geoffroy, Elyse Gregga, Isabelle Mulford, Ashley J Aguet, Francois Ardlie, Kristin Gerszten, Robert Clish, Clary Van Den Berg, David Taylor, Kent D Durda, Peter Johnson, W Craig Cornell, Elaine Guo, Xiuqing Liu, Yongmei Tracy, Russell Conomos, Matthew Blackwell, Tom Papanicolaou, George Lappalainen, Tuuli Mikhaylova, Anna V Thornton, Timothy A Cho, Michael H Gignoux, Christopher R Lange, Leslie Lange, Ethan Rich, Stephen S Rotter, Jerome I Manichaikul, Ani Im, Hae Kyung Wheeler, Heather E eng R15 HG/HG/NHGRI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't PLoS One. Feb 24;17(2):e. doi: 10./journal.pone.. eCollection .I SomaScan 02/25/ Povero D, et al. Protein and miRNA profile of circulating extracellular vesicles in patients with primary sclerosing cholangitis Sci Rep 12 1 https://www.doi.org/10./s-022--0 35,194,091 Adult Aged Biomarkers/blood Cholangitis, Sclerosing/*diagnosis Extracellular Vesicles/*genetics/*metabolism Female Gene Expression Humans Interleukin-13 Receptor alpha1 Subunit/*genetics/*metabolism Liver Cirrhosis/diagnosis Male MicroRNAs/*genetics/*metabolism Middle Aged Young Adult Primary sclerosing cholangitis (PSC) is an idiopathic and heterogenous cholestatic liver disease characterized by chronic inflammation and fibrosis of the biliary tree. Currently, no effective therapies are available for this condition, whose incidence is rising. At present, specificity and sensitivity of current serum markers used to diagnose PSC are limited and often unreliable. In this study, we characterize circulating extracellular vesicles and provide supporting data on their potential use as novel surrogate biomarkers for PSC. EVs are membrane surrounded structures, 100- nm in size, released by cells under various conditions and which carry a variety of bioactive molecules, including small non-coding RNAs, lipids and proteins. In recent years, a large body of evidence has pointed to diagnostic implications of EVs and relative cargo in various human diseases. We isolated EVs from serum of well-characterized patients with PSC or control subjects by differential centrifugation and size-exclusion chromatography. A complete characterization identified elevated levels of circulating EVs in PSC patients compared to healthy control subjects ( vs. 500 Calcein-FITC + EVs/muL). Tissue and cell specificity of circulating EVs was assessed by identification of liver-specific markers and cholangiocyte marker CK-19. Further molecular characterization identified 282 proteins that were differentially regulated in PSC-derived compared to healthy control-EVs. Among those, IL-13Ra1 was the most significantly and differentially expressed protein in PSC-derived EVs and correlated with the degree of liver fibrosis. In addition to protein profiling, we performed a miRNA-sequencing analysis which identified 11 among established, liver-specific (e.g., miR-122 and miR-192) and novel miRNAs. One of the newly identified miRNAs, miR--3p, was significantly up-regulated fourfold in PSC-derived EVs compared to circulating EVs isolated from healthy controls. This study provides supporting evidence of the potential role of circulating EVs and associated protein and miRNA cargo as surrogate noninvasive and reliable biomarker for PSC. Povero, Davide Tameda, Masahiko Eguchi, Akiko Ren, Wenhua Kim, Jihoon Myers, Robert Goodman, Zachary D Harrison, Stephen A Sanyal, Arun J Bosch, Jaime Ohno-Machado, Lucila Feldstein, Ariel E eng Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England Sci Rep. Feb 22;12(1):. doi: 10./s-022--0.I SomaScan 02/24/ Chen G, et al. Identification of Distinct Inflammatory Programs and Biomarkers in Systemic Juvenile Idiopathic Arthritis and Related Lung Disease by Serum Proteome Analysis Arthritis Rheumatol 74 7 - https://www.doi.org/10./art. 35,189,047 *Arthritis, Juvenile/complications Biomarkers Humans *Lung Diseases/epidemiology *Macrophage Activation Syndrome Matrix Metalloproteinase 7 Proteome OBJECTIVE: Recent observations in systemic juvenile idiopathic arthritis (JIA) suggest an increasing incidence of high-mortality interstitial lung disease often characterized by a variant of pulmonary alveolar proteinosis (PAP). Co-occurrence of macrophage activation syndrome (MAS) and PAP in systemic JIA suggests a shared pathology, but patients with lung disease associated with systemic JIA (designated SJIA-LD) also commonly experience features of drug reaction such as atypical rashes and eosinophilia. This study was undertaken to investigate immunopathology and identify biomarkers in systemic JIA, MAS, and SJIA-LD. METHODS: We used SOMAscan to measure ~1,300 analytes in sera from healthy controls and patients with systemic JIA, MAS, SJIA-LD, or other related diseases. We verified selected findings by enzyme-linked immunosorbent assay and lung immunostaining. Because the proteome of a sample may reflect multiple states (systemic JIA, MAS, or SJIA-LD), we used regression modeling to identify subsets of altered proteins associated with each state. We tested key findings in a validation cohort. RESULTS: Proteome alterations in active systemic JIA and MAS overlapped substantially, including known systemic JIA biomarkers such as serum amyloid A and S100A9, and novel elevations in the levels of heat-shock proteins and glycolytic enzymes. Interleukin-18 levels were elevated in all systemic JIA groups, particularly MAS and SJIA-LD. We also identified an MAS-independent SJIA-LD signature notable for elevated levels of intercellular adhesion molecule 5 (ICAM-5), matrix metalloproteinase 7 (MMP-7), and allergic/eosinophilic chemokines, which have been previously associated with lung damage. Immunohistochemistry localized ICAM-5 and MMP-7 in the lungs of patients with SJIA-LD. The ability of ICAM-5 to distinguish SJIA-LD from systemic JIA/MAS was independently validated. CONCLUSION: Serum proteins support a systemic JIA-to-MAS continuum; help distinguish systemic JIA, systemic JIA/MAS, and SJIA-LD; and suggest etiologic hypotheses. Select biomarkers, such as ICAM-5, could aid in early detection and management of SJIA-LD. Chen, Guangbo Deutsch, Gail H Schulert, Grant S Zheng, Hong Jang, SoRi Trapnell, Bruce Lee, Pui Y Macaubas, Claudia Ho, Katherine Schneider, Corinne Saper, Vivian E de Jesus, Adriana Almeida Krasnow, Mark A Grom, Alexei Goldbach-Mansky, Raphaela Khatri, Purvesh Mellins, Elizabeth D Canna, Scott W eng R01 HD/HD/NICHD NIH HHS/ R01 AR/AR/NIAMS NIH HHS/ R01 AR/AR/NIAMS NIH HHS/ U19 AI/AI/NIAID NIH HHS/ R01 AI/AI/NIAID NIH HHS/ U19 AI/AI/NIAID NIH HHS/ K22 AI/AI/NIAID NIH HHS/ Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Arthritis Rheumatol. Jul;74(7):-. doi: 10./art.. Epub May 31.I SomaScan 02/22/ Sacco K, et al. Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19 Nat Med 28 5 - https://www.doi.org/10./s-022--3 35,177,862 *COVID-19/complications/genetics Child Humans SARS-CoV-2 Systemic Inflammatory Response Syndrome/genetics T-Lymphocytes Pediatric Coronavirus Disease (pCOVID-19) is rarely severe; however, a minority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might develop multisystem inflammatory syndrome in children (MIS-C), with substantial morbidity. In this longitudinal multi-institutional study, we applied multi-omics (analysis of soluble biomarkers, proteomics, single-cell gene expression and immune repertoire analysis) to profile children with COVID-19 (n = 110) and MIS-C (n = 76), along with pediatric healthy controls (pHCs; n = 76). pCOVID-19 was characterized by robust type I interferon (IFN) responses, whereas prominent type II IFN-dependent and NF-kappaB-dependent signatures, matrisome activation and increased levels of circulating spike protein were detected in MIS-C, with no correlation with SARS-CoV-2 PCR status around the time of admission. Transient expansion of TRBV11-2 T cell clonotypes in MIS-C was associated with signatures of inflammation and T cell activation. The association of MIS-C with the combination of HLA A*02, B*35 and C*04 alleles suggests genetic susceptibility. MIS-C B cells showed higher mutation load than pCOVID-19 and pHC. These results identify distinct immunopathological signatures in pCOVID-19 and MIS-C that might help better define the pathophysiology of these disorders and guide therapy. Sacco, Keith Castagnoli, Riccardo Vakkilainen, Svetlana Liu, Can Delmonte, Ottavia M Oguz, Cihan Kaplan, Ian M Alehashemi, Sara Burbelo, Peter D Bhuyan, Farzana de Jesus, Adriana A Dobbs, Kerry Rosen, Lindsey B Cheng, Aristine Shaw, Elana Vakkilainen, Mikko S Pala, Francesca Lack, Justin Zhang, Yu Fink, Danielle L Oikonomou, Vasileios Snow, Andrew L Dalgard, Clifton L Chen, Jinguo Sellers, Brian A Montealegre Sanchez, Gina A Barron, Karyl Rey-Jurado, Emma Vial, Cecilia Poli, Maria Cecilia Licari, Amelia Montagna, Daniela Marseglia, Gian Luigi Licciardi, Francesco Ramenghi, Ugo Discepolo, Valentina Lo Vecchio, Andrea Guarino, Alfredo Eisenstein, Eli M Imberti, Luisa Sottini, Alessandra Biondi, Andrea Mato, Sayonara Gerstbacher, Dana Truong, Meng Stack, Michael A Magliocco, Mary Bosticardo, Marita Kawai, Tomoki Danielson, Jeffrey J Hulett, Tyler Askenazi, Manor Hu, Shaohui Cohen, Jeffrey I Su, Helen C Kuhns, Douglas B Lionakis, Michail S Snyder, Thomas M Holland, Steven M Goldbach-Mansky, Raphaela Tsang, John S Notarangelo, Luigi D eng ZIA AI/ImNIH/Intramural NIH HHS/ Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Nat Med. May;28(5):-. doi: 10./s-022--3. Epub Feb 17.I SomaScan 02/19/ Ding Z, et al. Proteomics technologies for cancer liquid biopsies Mol Cancer 21 1 53 https://www.doi.org/10./s-022--8 35,168,611 Early Detection of Cancer Humans Liquid Biopsy *Neoplasms/diagnosis/genetics Proteome/metabolism *Proteomics/methods Antibody arrays Aptamer Cancer liquid biopsy Mass spectrometry (MS) Proteomics Proximity extension assay (PEA) Reverse phase protein arrays (RPPA) declare no conflicts of interests and no competing interests of this work. Alterations in DNAs could not reveal what happened in proteins. The accumulated alterations of DNAs would change the manifestation of proteins. Therefore, as is the case in cancer liquid biopsies, deep proteome profiling will likely provide invaluable and clinically relevant information in real-time throughout all stages of cancer progression. However, due to the great complexity of proteomes in liquid biopsy samples and the limitations of proteomic technologies compared to high-plex sequencing technologies, proteomic discoveries have yet lagged behind their counterpart, genomic technologies. Therefore, novel protein technologies are in urgent demand to fulfill the goals set out for biomarker discovery in cancer liquid biopsies.Notably, conventional and innovative technologies are being rapidly developed for proteomic analysis in cancer liquid biopsies. These advances have greatly facilitated early detection, diagnosis, prognosis, and monitoring of cancer evolution, adapted or adopted in response to therapeutic interventions. In this paper, we review the high-plex proteomics technologies that are capable of measuring at least hundreds of proteins simultaneously from liquid biopsy samples, ranging from traditional technologies based on mass spectrometry (MS) and antibody/antigen arrays to innovative technologies based on aptamer, proximity extension assay (PEA), and reverse phase protein arrays (RPPA). Ding, Zhiyong Wang, Nan Ji, Ning Chen, Zhe-Sheng eng Research Support, Non-U.S. Gov't Review England Mol Cancer. Feb 15;21(1):53. doi: 10./s-022--8.I SomaScan 02/17/ Essone PN, et al. Creatine kinase-(MB) and hepcidin as candidate biomarkers for early diagnosis of pulmonary tuberculosis: a proof-of-concept study in Lambarene, Gabon Infection 50 4 897-905 https://www.doi.org/10./s-022--8 35,133,607 Biomarkers Creatine Kinase, MB Form Early Diagnosis Gabon Hepcidins Humans *Mycobacterium tuberculosis ROC Curve Sensitivity and Specificity *Tuberculosis/diagnosis *Tuberculosis, Pulmonary/diagnosis Creatine kinase-MB Diagnosis Hepcidin Tuberculosis BACKGROUND: The present study aimed to evaluate the diagnostic utility of creatine kinase-MB (CK-MB), hepcidin (HEPC), phospholipase A2 group IIA (PLa2G2A), and myosin-binding protein C (MYBPC1) for tuberculosis (TB). These four biomarkers are differentially regulated between quiescent Mycobacterium tuberculosis (Mtb) infected individuals (non-progressors to TB disease) and Mtb-infected TB disease progressors 6 months before the onset of symptoms. METHODS: We enrolled samples from patients experiencing moderate-to-severe pulmonary infections diseases including 23 TB cases confirmed by smear microscopy and culture, and 34 TB-negative cases. For each participant, the serum levels of the four biomarkers were measured using ELISA. RESULTS: The levels of CK-MB and HEPC were significantly reduced in patients with active TB disease. CK-MB median level was pg/ml (- pg/ml) in active TB cases and pg/ml (- pg/ml) in non-TB pulmonary diseases. Using the receiver operating characteristic curve (ROC) analysis, HEPC and CK-MB had the Area Under the Curve (AUC) of 79% (95% CI 67-91%) and 81% (95% CI 69-93%), respectively. Both markers correlated with TB diagnosis as a single marker. PLa2G2A and MYBPC1 with AUCs of 48% (95% CI 36-65%) and 62% (95% CI 48-76%) did not performed well as single biomarkers. The three markers'model (CK-MB-HEPC-PLa2G2A) had the highest diagnostic accuracy at 82% (95% CI 56-82%) after cross-validation. CONCLUSION: CK-MB and HEPC levels were statistically different between confirmed TB cases and non-TB cases. This study yields promising results for the rapid diagnosis of TB disease using a single marker or three biomarkers model. Essone, Paulin N Adegbite, Bayode R Mbadinga, Marien J M Mbouna, Armel V Lotola-Mougeni, Fabrice Alabi, Ayodele Edoa, Jean R Lell, Bertrand Alabi, Abraham S Adegnika, Ayola A Ramharter, Michael Siawaya, Joel F D Grobusch, Martin P Kremsner, Peter G Agnandji, Selidji T eng EDCTP-TMA-SF--VARSAF/European and Developing Countries Clinical Trials Partnership/ Germany Infection. Aug;50(4):897-905. doi: 10./s-022--8. Epub Feb 8.I SomaScan 02/09/ Schreiner C, et al. Placental proteins with predicted roles in fetal development decrease in premature infants Pediatr Res 92 5 - https://www.doi.org/10./s-022--y 35,132,128 Female Humans Infant, Newborn Pregnancy Fetal Blood Fetal Development *Infant, Premature Placenta/metabolism *Pregnancy Proteins BACKGROUND: Emerging evidence from animal experiments indicate that factors secreted by the placenta are critical for normal fetal organ development. Our objective was to characterize the umbilical vein and artery proteome in preterm infants and identify proteins that decrease in the neonatal circulation following delivery. METHODS: Cord blood at delivery and neonatal blood at 48-72 h of life was collected in 25 preterm infants. Plasma protein abundance was determined using the SomaLogic platform. RESULTS: When comparing protein levels of umbilical venous to arterial cord blood, 434 proteins were significantly higher indicating placental secretion into the fetal circulation. Moreover, when comparing neonatal blood to umbilical vein levels, 142 proteins were significantly lower. These proteins included Endoplasmic reticulum resident protein 29, CD59, Fibroblast growth factor 2 and Dynactin subunit 2, which are involved in brain development and prevention of brain damage as well as Fibroblast growth factor 1 which prevents lung fibrosis. CONCLUSIONS: The late second trimester human placenta secretes proteins into the fetal circulation which decrease following delivery. Many of these proteins are predicted to be important in the development of fetal organs. Further studies are needed to directly link placental proteins to organ development and poor outcomes in preterm infants. IMPACT: Prematurity remains a leading cause of morbidity and mortality requiring the development of novel treatments. Emerging evidence from animal studies suggest that factors secreted from the placenta may be critical in the development of the fetus. We report that the preterm human placenta secretes an array of proteins into the fetal circulation. Some of these proteins are predicted to be involved in the development of the brain and the lung. When born prematurely, infants are deprived of these placental proteins, which may contribute to their poor outcomes. Schreiner, Cynthia Powell, Theresa L Palmer, Claire Jansson, Thomas eng R21 HD/HD/NICHD NIH HHS/ Pediatr Res. Nov;92(5):-. doi: 10./s-022--y. Epub Feb 7.I SomaScan 02/09/ Mookherjee N, et al. Defining the effects of traffic-related air pollution on the human plasma proteome using an aptamer proteomic array: A dose-dependent increase in atherosclerosis-related proteins Environ Res 209 https://www.doi.org/10./j.envres.. 35,120,890 *Air Pollutants/analysis/toxicity *Air Pollution/adverse effects/analysis *Atherosclerosis/chemically induced/etiology/metabolism Humans Proteome Proteomics Random Allocation Vehicle Emissions/analysis/toxicity Air pollution Atherosclerosis Biomarkers Diesel exhaust BACKGROUND: Traffic-related air pollution (TRAP) is a critical risk factor and major contributor to respiratory and cardiovascular disease (CVD). The effects of TRAP beyond the lungs can be related to changes in circulatory proteins. However, such TRAP-mediated changes have not been defined in an unbiased manner using a controlled human model. OBJECTIVE: To detail global protein changes (the proteome) in plasma following exposure to inhaled diesel exhaust (DE), a paradigm of TRAP, using controlled human exposures. METHODS: In one protocol, ex-smokers and never-smokers were exposed to filtered air (FA) and DE (300 mug PM(2.5)/m(3)), on order-randomized days, for 2 h. In a second protocol, independent never-smoking participants were exposed to lower concentrations of DE (20, 50 or 150 mug PM(2.5)/m(3)) and FA, for 4 h, on order-randomized days. Each exposure was separated by 4 weeks of washout. Plasma samples obtained 24 h post-exposure from ex-smokers (n = 6) were first probed using Slow off-rate modified aptamer proteomic array. Plasma from never-smokers (n = 11) was used for independent assessment of proteins selected from the proteomics study by immunoblotting. RESULTS: Proteomics analyses revealed that DE significantly altered 342 proteins in plasma of ex-smokers (n = 6). The top 20 proteins therein were primarily associated with inflammation and CVD. Plasma from never-smokers (n = 11) was used for independent assessment of 6 proteins, amongst the top 10 proteins increased by DE in the proteomics study, for immunoblotting. The abundance of all six proteins (fractalkine, apolipoproteins (APOB and APOM), IL18R1, MIP-3 and MMP-12) was significantly increased by DE in plasma of these never-smokers. DE-mediated increase was shown to be concentration-dependent for fractalkine, APOB and MMP-12, all biomarkers of atherosclerosis, which correlated with plasma levels of IL-6, a subclinical marker of CVD, in independent participants. CONCLUSION: This investigation details changes in the human plasma proteome due to TRAP. We identify specific atherosclerosis-related proteins that increase concentration-dependently across a range of TRAP levels applicable worldwide. Mookherjee, Neeloffer Ryu, Min Hyung Hemshekhar, Mahadevappa Orach, Juma Spicer, Victor Carlsten, Christopher eng Netherlands Environ Res. Jun;209:. doi: 10./j.envres... Epub Feb 1.I SomaScan 02/06/ Bjornsdottir G, et al. Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology Nat Commun 13 1 634 https://www.doi.org/10./s-022--1 35,110,524 3' Untranslated Regions Bone and Bones/metabolism Genome-Wide Association Study Humans Intervertebral Disc/*metabolism Intervertebral Disc Degeneration/*genetics Intervertebral Disc Displacement/*genetics Sodium Sulfate Cotransporter/*genetics/*metabolism Sulfates/*metabolism Symporters/genetics/metabolism Back pain is a common and debilitating disorder with largely unknown underlying biology. Here we report a genome-wide association study of back pain using diagnoses assigned in clinical practice; dorsalgia (119,100 cases, 909,847 controls) and intervertebral disc disorder (IDD) (58,854 cases, 922,958 controls). We identify 41 variants at 33 loci. The most significant association (OR(IDD) = 0.92, P = 1.6 x 10(-39); OR(dorsalgia) = 0.92, P = 7.2 x 10(-15)) is with a 3'UTR variant (rs-T) in CHST3, encoding a sulfotransferase enzyme expressed in intervertebral discs. The largest effects on IDD are conferred by rare (MAF = 0.07 - 0.32%) loss-of-function (LoF) variants in SLC13A1, encoding a sodium-sulfate co-transporter (LoF burden OR = 1.44, P = 3.1 x 10(-11)); variants that also associate with reduced serum sulfate. Genes implicated by this study are involved in cartilage and bone biology, as well as neurological and inflammatory processes. Bjornsdottir, Gyda Stefansdottir, Lilja Thorleifsson, Gudmar Sulem, Patrick Norland, Kristjan Ferkingstad, Egil Oddsson, Asmundur Zink, Florian Lund, Sigrun H Nawaz, Muhammad S Bragi Walters, G Skuladottir, Astros Th Gudjonsson, Sigurjon A Einarsson, Gudmundur Halldorsson, Gisli H Bjarnadottir, Valgerdur Sveinbjornsson, Gardar Helgadottir, Anna Styrkarsdottir, Unnur Gudmundsson, Larus J Pedersen, Ole B Hansen, Thomas Folkmann Werge, Thomas Banasik, Karina Troelsen, Anders Skou, Soren T Thorner, Lise Wegner Erikstrup, Christian Nielsen, Kaspar Rene Mikkelsen, Susan Jonsdottir, Ingileif Bjornsson, Aron Olafsson, Ingvar H Ulfarsson, Elfar Blondal, Josep Vikingsson, Arnor Brunak, Soren Ostrowski, Sisse R Ullum, Henrik Thorsteinsdottir, Unnur Stefansson, Hreinn Gudbjartsson, Daniel F Thorgeirsson, Thorgeir E Stefansson, Kari eng Research Support, Non-U.S. Gov't England Nat Commun. Feb 2;13(1):634. doi: 10./s-022--1.I SomaScan 02/04/ Schunkert H, et al. Linking Genetics and Proteomics: Gene-Protein Associations Built on Diversity Circulation 145 5 371-374 https://www.doi.org/10./CIRCULATIONAHA.121. 35,100,019 Genome-Wide Association Study *Genomics Humans *Proteomics Editorials cardiovascular disease ethnic diversity genomics proteomics Schunkert, Heribert Mayr, Manuel eng SP/17/10//BHF_/British Heart Foundation/United Kingdom RG/16/14//BHF_/British Heart Foundation/United Kingdom CH/16/3//BHF_/British Heart Foundation/United Kingdom Comment Editorial Research Support, Non-U.S. Gov't Circulation. Feb;145(5):371-374. doi: 10./CIRCULATIONAHA.121.. Epub Jan 31.I SomaScan 02/01/ Vanarsa K, et al. Aptamer-Based Screen of Neuropsychiatric Lupus Cerebrospinal Fluid Reveals Potential Biomarkers That Overlap With the Choroid Plexus Transcriptome Arthritis Rheumatol 74 7 - https://www.doi.org/10./art. 35,099,126 *Biomarkers/cerebrospinal fluid Choroid Plexus/metabolism Complement C3/metabolism Humans Immunoglobulin M/metabolism Lipocalin-2/metabolism *Lupus Vasculitis, Central Nervous System/cerebrospinal fluid/diagnosis Macrophage Colony-Stimulating Factor/metabolism Proteomics Transcriptome OBJECTIVE: As no gold-standard diagnostic test exists for neuropsychiatric systemic lupus erythematosus (NPSLE), we undertook this study to execute a broad screen of NPSLE cerebrospinal fluid (CSF) using an aptamer-based platform. METHODS: CSF was obtained from NPSLE patients and subjected to proteomic assay using the aptamer-based screen. Potential biomarkers were identified and validated in independent NPSLE cohorts in comparison to other neurologic diseases. RESULTS: Forty proteins out of the 1,129 screened were found to be elevated in NPSLE CSF. Based on enzyme-linked immunosorbent assay validation, CSF levels of angiostatin, alpha2-macroglobulin, DAN, fibronectin, hepatocellular carcinoma clone 1, IgM, lipocalin 2, macrophage colony-stimulating factor (M-CSF), and serine protease inhibitor G1 were significantly elevated in a predominantly White NPSLE cohort (n = 24), compared to patients with other neurologic diseases (n = 54), with CSF IgM (area under the curve [AUC] 0.95) and M-CSF (AUC 0.91) being the most discriminatory proteins. In a second Hong Kong-based NPSLE cohort, CSF IgM (AUC 0.78) and lipocalin 2 (AUC 0.85) were the most discriminatory proteins. Several CSF proteins exhibited high diagnostic specificity for NPSLE in both cohorts. Elevated CSF complement C3 was associated with an acute confusional state. Eleven molecules elevated in NPSLE CSF exhibited concordant elevation in the choroid plexus, suggesting shared origins. CONCLUSION: Lipocalin 2, M-CSF, IgM, and complement C3 emerge as promising CSF biomarkers of NPSLE with diagnostic potential. Vanarsa, Kamala Sasidharan, Prashanth Duran, Valeria Gokaraju, Sirisha Nidhi, Malavika Titus, Anto Sam Crosslee Louis Sam Soomro, Sanam Stock, Ariel D Der, Evan Putterman, Chaim Greenberg, Benjamin Mok, Chi Chiu Hanly, John G Mohan, Chandra eng R01 AR/GF/NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Arthritis Rheumatol. Jul;74(7):-. doi: 10./art.. Epub May 18.I SomaScan 02/01/ Emilsson V, et al. Coding and regulatory variants are associated with serum protein levels and disease Nat Commun 13 1 481 https://www.doi.org/10./s-022--6 35,079,000 Aged Blood Proteins/*genetics Disease/classification/*genetics Exome/*genetics Female *Genetic Predisposition to Disease *Genotype Humans Iceland Male *Polymorphism, Single Nucleotide Proteome/*metabolism Circulating proteins can be used to diagnose and predict disease-related outcomes. A deep serum proteome survey recently revealed close associations between serum protein networks and common disease. In the current study, 54,469 low-frequency and common exome-array variants were compared to protein measurements in the serum of individuals from the AGES Reykjavik cohort. This analysis identifies a large number of serum proteins with genetic signatures overlapping those of many diseases. More specifically, using a study-wide significance threshold, we find that independent exome array variants are associated with serum levels of proteins. These variants reside in genetic loci shared by hundreds of complex disease traits, highlighting serum proteins' emerging role as biomarkers and potential causative agents of a wide range of diseases. Emilsson, Valur Gudmundsdottir, Valborg Gudjonsson, Alexander Jonmundsson, Thorarinn Jonsson, Brynjolfur G Karim, Mohd A Ilkov, Marjan Staley, James R Gudmundsson, Elias F Launer, Lenore J Lindeman, Jan H Morton, Nicholas M Aspelund, Thor Lamb, John R Jennings, Lori L Gudnason, Vilmundur eng N01AG/AG/NIA NIH HHS/ /WT_/Wellcome Trust/United Kingdom R01 AG/AG/NIA NIH HHS/ WT_/Wellcome Trust/United Kingdom HHSNC/DA/NIDA NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England Nat Commun. Jan 25;13(1):481. doi: 10./s-022--6.I SomaScan 01/27/ Gudjonsson A, et al. A genome-wide association study of serum proteins reveals shared loci with common diseases Nat Commun 13 1 480 https://www.doi.org/10./s-021--z 35,078,996 Aged Aged, 80 and over Blood Proteins/*genetics Cohort Studies Disease/classification/*genetics Female *Genetic Predisposition to Disease *Genome, Human Genome-Wide Association Study/*methods Humans Iceland Male *Polymorphism, Single Nucleotide *Quantitative Trait Loci With the growing number of genetic association studies, the genotype-phenotype atlas has become increasingly more complex, yet the functional consequences of most disease associated alleles is not understood. The measurement of protein level variation in solid tissues and biofluids integrated with genetic variants offers a path to deeper functional insights. Here we present a large-scale proteogenomic study in 5,368 individuals, revealing 4,035 independent associations between genetic variants and 2,091 serum proteins, of which 36% are previously unreported. The majority of both cis- and trans-acting genetic signals are unique for a single protein, although our results also highlight numerous highly pleiotropic genetic effects on protein levels and demonstrate that a protein's genetic association profile reflects certain characteristics of the protein, including its location in protein networks, tissue specificity and intolerance to loss of function mutations. Integrating protein measurements with deep phenotyping of the cohort, we observe substantial enrichment of phenotype associations for serum proteins regulated by established GWAS loci, and offer new insights into the interplay between genetics, serum protein levels and complex disease. Gudjonsson, Alexander Gudmundsdottir, Valborg Axelsson, Gisli T Gudmundsson, Elias F Jonsson, Brynjolfur G Launer, Lenore J Lamb, John R Jennings, Lori L Aspelund, Thor Emilsson, Valur Gudnason, Vilmundur eng HHSNC/DA/NIDA NIH HHS/ N01AG/AG/NIA NIH HHS/ R01 AG/AG/NIA NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England Nat Commun. Jan 25;13(1):480. doi: 10./s-021--z.I SomaScan 01/27/ Rhodes CJ, et al. Using the Plasma Proteome for Risk Stratifying Patients with Pulmonary Arterial Hypertension Am J Respir Crit Care Med 205 9 - https://www.doi.org/10./rccm.-OC 35,081,018 Area Under Curve Biomarkers Familial Primary Pulmonary Hypertension Humans Natriuretic Peptide, Brain Peptide Fragments Prognosis Proteome *Pulmonary Arterial Hypertension clinical outcomes Rationale: NT-proBNP (N-terminal pro-brain natriuretic peptide), a biomarker of cardiac origin, is used to risk stratify patients with pulmonary arterial hypertension (PAH). Its limitations include poor sensitivity to early vascular pathology. Other biomarkers of vascular or systemic origin may also be useful in the management of PAH. Objectives: Identify prognostic proteins in PAH that complement NT-proBNP and clinical risk scores. Methods: An aptamer-based assay (SomaScan version 4) targeting 4,152 proteins was used to measure plasma proteins in patients with idiopathic, heritable, or drug-induced PAH from the UK National Cohort of PAH (n = 357) and the French EFORT (Evaluation of Prognostic Factors and Therapeutic Targets in PAH) study (n = 79). Prognostic proteins were identified in discovery-replication analyses of UK samples. Proteins independent of 6-minute-walk distance and NT-proBNP entered least absolute shrinkage and selection operator modeling, and the best combination in a single score was evaluated against clinical targets in EFORT. Measurements and Main Results: Thirty-one proteins robustly informed prognosis independent of NT-proBNP and 6-minute-walk distance in the UK cohort. A weighted combination score of six proteins was validated at baseline (5-yr mortality; area under the curve [AUC], 0.73; 95% confidence interval [CI], 0.63-0.85) and follow-up in EFORT (AUC, 0.84; 95% CI, 0.75-0.94; P = 9.96 x 10(-6)). The protein score risk stratified patients independent of established clinical targets and risk equations. The addition of the six-protein model score to NT-proBNP improved prediction of 5-year outcomes from AUC 0.762 (0.702-0.821) to 0.818 (0.767-0.869) by receiver operating characteristic analysis (P = 0. for difference in AUC) in the UK replication and French samples combined. Conclusions: The plasma proteome informs prognosis beyond established factors in PAH and may provide a more sensitive measure of therapeutic response. Rhodes, Christopher J Wharton, John Swietlik, Emilia M Harbaum, Lars Girerd, Barbara Coghlan, J Gerry Lordan, James Church, Colin Pepke-Zaba, Joanna Toshner, Mark Wort, Stephen J Kiely, David G Condliffe, Robin Lawrie, Allan Graf, Stefan Montani, David Boucly, Athenais Sitbon, Olivier Humbert, Marc Howard, Luke S Morrell, Nicholas W Wilkins, Martin R eng FS/15/59//BHF_/British Heart Foundation/United Kingdom MR/K/1/MRC_/Medical Research Council/United Kingdom FS/13/48//BHF_/British Heart Foundation/United Kingdom FS/18/52//BHF_/British Heart Foundation/United Kingdom RE/18/4//BHF_/British Heart Foundation/United Kingdom SP/12/12//BHF_/British Heart Foundation/United Kingdom DH_/Department of Health/United Kingdom SP/18/10//BHF_/British Heart Foundation/United Kingdom Research Support, Non-U.S. Gov't Am J Respir Crit Care Med. May 1;205(9):-. doi: 10./rccm.-OC.I SomaScan 01/27/ Sproull M, et al. Comparison of Proteomic Expression Profiles after Radiation Exposure across Four Different Species Radiat Res 197 4 315-323 https://www.doi.org/10./RADE-21-.1 35,073,400 Animals Biomarkers/metabolism Dose-Response Relationship, Radiation Histones Humans Mice Mice, Inbred C57BL *Proteomics *Radiation Exposure/adverse effects/analysis Swine Swine, Miniature There is a need to identify biomarkers of radiation exposure for use in development of circulating biodosimeters for radiation exposure and for clinical use as markers of radiation injury. Most research approaches for biomarker discovery rely on a single animal model. The current study sought to take advantage of a novel aptamer-based proteomic assay which has been validated for use in many species to characterize changes to the blood proteome after total-body irradiation (TBI) across four different mammalian species including humans. Plasma was collected from C57BL6 mice, Sinclair minipigs, and Rhesus non-human primates (NHPs) receiving a single dose of TBI at a range of 3.3 Gy to 4.22 Gy at 24 h postirradiation. NHP and minipig models were irradiated using a 60Co source at a dose rate of 0.6 Gy/min, the C57BL6 mouse model using an X-ray source at a dose rate of 2.28 Gy/min and clinical samples from a photon source at 10 cGy/min. Plasma was collected from human patients receiving a single dose of 2 Gy TBI collected 6 h postirradiation. Plasma was screened using the aptamer-based SomaLogic SomaScan(R) proteomic assay technology to evaluate changes in the expression of 1,310 protein analytes. Confirmatory analysis of protein expression of biomarker HIST1H1C, was completed using plasma from C57BL6 mice receiving a 2, 3.5 or 8 Gy TBI collected at days 1, 3, and 7 postirradiation by singleplex ELISA. Summary of key pathways with altered expression after radiation exposure across all four mammalian species was determined using Ingenuity Pathway Analysis (IPA). Detectable values were obtained for all 1,310 proteins in all samples included in the SomaScan assay. A subset panel of protein biomarkers which demonstrated significant (p 2 or /= 0.90. Immunostaining was used to characterize the cellular localization of the new biomarker proteins in liver tissues. We identified nine proteins in the discovery cohort (n = 40 subjects) and five proteins in the validation cohort (n = 80 subjects) that individually or in combination predicted clinical PHT with AUROCs >/= 0.90. Merging the two cohorts, we found that semaphorin 6B (SEMA6B) alone and three other protein combinations (SEMA6B+secreted frizzle protein 3 [SFRP3], SEMA6B+COMM domain containing 7 [COMMD7], and vascular cell adhesion molecule 1 [VCAM1]+BMX nonreceptor tyrosine kinase [BMX]) had AUROCs >/= 0.90 in both cohorts, with high positive- and negative-predictive values. Immunostaining of the new protein biomarkers showed increased expression in hepatic endothelial cells, cholangiocytes, and immune cells within portal triads in BA livers with clinical PHT compared to healthy livers. Conclusion: Large-scale proteomics identified SEMA6B, SFRP3, COMMD7, BMX, and VCAM1 as biomarkers highly associated with clinical PHT in BA. The expression of the biomarkers in hepatic epithelial, endothelial, and immune cells support their potential role in the pathophysiology of PHT. Osborn, Julie Mourya, Reena Thanekar, Unmesha Su, Weizhe Fei, Lin Shivakumar, Pranavkumar Bezerra, Jorge A eng T32 DK/DK/NIDDK NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Hepatol Commun. May;6(5):995-. doi: 10./hep4.. Epub Dec 27.I SomaScan 12/29/ Rahman ML, et al. Proteomic analysis of serum in workers exposed to diesel engine exhaust Environ Mol Mutagen 63 1 18-28 https://www.doi.org/10./em. 34,894,159 *Air Pollutants, Occupational/analysis/toxicity Carbon/analysis/metabolism Cross-Sectional Studies Group IB Phospholipases A2/metabolism Humans Inflammation/metabolism *Occupational Exposure/adverse effects/analysis Proteomics RNA-Binding Proteins/analysis Vehicle Emissions/analysis/toxicity SOMAscan carcinogenesis diesel engine exhaust elemental carbon lung cancer Diesel engine exhaust (DEE) is classified as a Group 1 human carcinogen. Using a targeted proteomics approach, we aimed to identify proteins associated with DEE and characterize these markers to understand the mechanisms of DEE-induced carcinogenicity. In this cross-sectional molecular epidemiology study, we measured elemental carbon (EC) using a personal air monitor and quantified targeted proteins in the serum using the SOMAScan assay (SOMALogic) among 19 diesel exposed factory workers and 19 unexposed controls. We used linear regressions to identify proteins associated with DEE and examined their exposure-response relationship across levels of EC using linear trend tests. We further examined pathway enrichment of DEE-related proteins using MetaCore. Occupational exposure to DEE was associated with altered levels of 22 serum proteins (permutation p /=5. Results were validated using an alternative, antibody-based, proteomic platform (Olink) as well as replicated in the Multi-Ethnic Study of Atherosclerosis and the HERITAGE Family Study (Health, Risk Factors, Exercise Training and Genetics). RESULTS: We identify 569 genetic associations between 479 proteins and 438 unique genetic regions at a Bonferroni-adjusted significance level of 3.8x10(-11). These associations include 114 novel locus-protein relationships and an additional 217 novel sentinel variant-protein relationships. Novel cardiovascular findings include new protein associations at the APOE gene locus including ZAP70 (sentinel single nucleotide polymorphism [SNP] rs-T, beta=0.61+/-0.05, P=3.27x10(-30)) and MMP-3 (beta=-0.60+/-0.05, P=1.67x10(-32)), as well as a completely novel pleiotropic locus at the HPX gene, associated with 9 proteins. Further, the associations suggest new mechanisms of genetically mediated cardiovascular disease linked to African ancestry; we identify a novel association between variants linked to APOL1-associated chronic kidney and heart disease and the protein CKAP2 (rs-G, beta=0.34+/-0.04, P=1.34x10(-17)) as well as an association between ATTR amyloidosis and RBP4 levels in community-dwelling individuals without heart failure. CONCLUSIONS: Taken together, these results provide evidence for the functional importance of variants in non-European populations, and suggest new biological mechanisms for ancestry-specific determinants of lipids, coagulation, and myocardial function. Katz, Daniel H Tahir, Usman A Bick, Alexander G Pampana, Akhil Ngo, Debby Benson, Mark D Yu, Zhi Robbins, Jeremy M Chen, Zsu-Zsu Cruz, Daniel E Deng, Shuliang Farrell, Laurie Sinha, Sumita Schmaier, Alec A Shen, Dongxiao Gao, Yan Hall, Michael E Correa, Adolfo Tracy, Russell P Durda, Peter Taylor, Kent D Liu, Yongmei Johnson, W Craig Guo, Xiuqing Yao, Jie Ida Chen, Yii-Der Manichaikul, Ani W Jain, Deepti Bouchard, Claude Sarzynski, Mark A Rich, Stephen S Rotter, Jerome I Wang, Thomas J Wilson, James G Natarajan, Pradeep Gerszten, Robert E (Trans-Omics for Precision Medicine) eng R01 NR/NR/NINR NIH HHS/ DP5 OD/OD/NIH HHS/ R01 DK/DK/NIDDK NIH HHS/ R01 HL/HL/NHLBI NIH HHS/ R01 HL/HL/NHLBI NIH HHS/ R01 HL/HL/NHLBI NIH HHS/ T32 HL/HL/NHLBI NIH HHS/ F32 HL/HL/NHLBI NIH HHS/ K08 HL/HL/NHLBI NIH HHS/ U01 DK/DK/NIDDK NIH HHS/ KL2 TR/TR/NCATS NIH HHS/ K08 HL/HL/NHLBI NIH HHS/ RF1 AG/AG/NIA NIH HHS/ K23 DK/DK/NIDDK NIH HHS/ R01 HL/HL/NHLBI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Circulation. Feb;145(5):357-370. doi: 10./CIRCULATIONAHA.121.. Epub Nov 24.I SomaScan 11/25/ Schuppan D, et al. Liquid biomarkers for fibrotic NASH - progress in a complex field J Hepatol 76 1 7-May https://www.doi.org/10./j.jhep..11.005 34,801,249 Biomarkers Fibrosis Humans *Non-alcoholic Fatty Liver Disease/diagnosis Companion biomarker Nafld fibrogenesis liver biopsy liver fibrosis prediction serum marker arrangement or affiliation with any organization that may have a direct influence on their work. Please refer to the accompanying ICMJE disclosure forms for further details. Schuppan, Detlef Myneni, Sudharani Surabattula, Rambabu eng Comment Editorial Research Support, Non-U.S. Gov't Netherlands J Hepatol. Jan;76(1):5-7. doi: 10./j.jhep..11.005. Epub Nov 17.I SomaScan 11/22/ Chelliah SS, et al. Identification of blood-based biomarkers for diagnosis and prognosis of Parkinson's disease: A systematic review of proteomics studies Ageing Res Rev 73 https://www.doi.org/10./j.arr.. 34,798,300 Biomarkers Dopaminergic Neurons Humans *Parkinson Disease/diagnosis Prognosis Proteomics Apolipoprotein A-I Apolipoproteins Blood-based biomarkers Parkinson's disease Systematic review Parkinson's Disease (PD), a neurodegenerative disorder, is characterised by the loss of motor function and dopamine neurons. Therapeutic avenues remain a challenge due to lack of accuracy in early diagnosis, monitoring of disease progression and limited therapeutic options. Proteomic platforms have been utilised to discover biomarkers for numerous diseases, a tool that may benefit the diagnosis and monitoring of disease progression in PD patients. Therefore, this systematic review focuses on analysing blood-based candidate biomarkers (CB) identified via proteomics platforms for PD. This study systematically reviewed articles across six databases (EMBASE, Cochrane, Ovid Medline, Scopus, Science Direct and PubMed) published between and . Of the 504 articles identified, 12 controlled-PD studies were selected for further analysis. A total of 115 candidate biomarkers (CB) were identified across selected 12-controlled studies, of which 23 CB were found to be replicable in more than two cohorts. Using the PANTHER Go-Slim classification system and STRING network, the gene function and protein interactions between biomarkers were analysed. Our analysis highlights Apolipoprotein A-I (ApoA-I), which is essential in lipid metabolism, oxidative stress, and neuroprotection demonstrates high replicability across five cohorts with consistent downregulation across four cohorts. Since ApoA-I was highly replicable across blood fractions, proteomic platforms and continents, its relationship with cholesterol, statin and oxidative stress as PD biomarker, its role in the pathogenesis of PD is discussed in this paper. The present study identified ApoA-I as a potential biomarker via proteomics analysis of PD for the early diagnosis and prediction of disease progression. Chelliah, Shalini Sundramurthi Bhuvanendran, Saatheeyavaane Magalingam, Kasthuri Bai Kamarudin, Muhamad Noor Alfarizal Radhakrishnan, Ammu Kutty eng Research Support, Non-U.S. Gov't Review Systematic Review England Ageing Res Rev. Jan;73:. doi: 10./j.arr... Epub Nov 16.I SomaScan 11/20/ Yousri NA, et al. Proteome-wide associations with short- and long-term weight loss and regain after Roux-en-Y gastric bypass surgery Obesity (Silver Spring) 30 1 129-141 https://www.doi.org/10./oby. 34,796,696 Body Mass Index Follow-Up Studies *Gastric Bypass/methods Humans *Obesity, Morbid/complications/surgery Proteome Retrospective Studies Treatment Outcome Weight Loss OBJECTIVE: Gastric bypass surgery results in long-term weight loss. Small studies have examined protein changes during rapid weight loss (up to 1 or 2 years post surgery). This study tested whether short-term changes were maintained after 12 years. METHODS: A 12-year follow-up, protein-wide association study of 1,297 SomaLogic aptamer-based plasma proteins compared short- (2-year) and long-term (12-year) protein changes in 234 individuals who had gastric bypass surgery with 144 nonintervened individuals with severe obesity. RESULTS: There were 51 replicated 12-year protein changes that differed between the surgery and nonsurgery groups. Adjusting for change in BMI, only 12 proteins remained significant, suggesting that BMI change was the primary reason for most protein changes and not non-BMI-related surgical effects. Protein changes were related to BMI changes during both weight-loss and weight-regain periods. The significant proteins were associated primarily with lipid, uric acid, or resting energy expenditure clinical variables and metabolic pathways. Eight protein changes were associated with 12-year diabetes remission, including apolipoprotein M, sex hormone binding globulin, and adiponectin (p /=65 y participating in the Invecchiare in Chianti (InCHIANTI) Study, plasma alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, zeaxanthin, and lycopene were measured using HPLC. The SOMAscan assay was used to measure plasma proteins. Multivariable linear regression models were used to examine the relationship of individual carotenoids and retinol with plasma proteins. A false discovery rate approach was used to deal with multiple comparisons using a q-value 5/16 atherosclerotic segments (CAD(+)) or completely clean arteries (CAD(-)) and either = 1 risk factor (RF(+)) or >/=3 risk factors (RF(-)) (based on history, blood pressure, glycemia, lipids, and smoking). RESULTS: Of 544 individuals, 39% were atypical (93 CAD(+)/RF(-); 120 CAD(-)/RF(+)) and 61% typical (102 CAD(+)/RF(+); 229 CAD(-)/RF(-)). In the comparison with CAD(+)/RF(-) adjusted for sex and age, CAD(-)/RF(+) was associated with increased atrial myosin regulatory light chain 2 (MYO) and C-C motif chemokine-22 (C-C-22), and reduced protein shisa-3 homolog (PS-3) and platelet-activating factor acetylhydrolase (PAF-AH). Extending the analysis to the entire cohort, an additional 8 proteins were independently associated with CAD or RF; by logistic regression, the 12-protein panel alone discriminated the four groups with AUC(ROC)'s of 0.72-0.81 (overall p = 1.0e(-38)). Among them, insulin-like growth factor binding protein-3 is positively associated with RF, lower BMI, and HDL-cholesterol, renin with CAD higher glycated hemoglobin HbA(1c), and smoking. CONCLUSIONS: In a CCTA-based cohort, four proteins, involved in opposing vascular processes (healing vs. adverse remodeling), are specifically associated with low CAD burden in high CV-risk individuals (high MYO and C-C-22) and high CAD burden in low-risk subjects (high PS-3 and PAF-AH), in interaction with BMI, smoking, diabetes, HDL-cholesterol, and HbA(1c). These findings could contribute to a deeper understanding of the atherosclerotic process beyond traditional risk profile assessment and potentially constitute new treatment targets. Ferrannini, Ele Manca, Maria Laura Ferrannini, Giulia Andreotti, Felicita Andreini, Daniele Latini, Roberto Magnoni, Marco Williams, Stephen A Maseri, Attilio Maggioni, Aldo P eng Switzerland Front Cardiovasc Med. Feb 4;8:. doi: 10./fcvm... eCollection .I SomaScan 02/22/ Wu L, et al. Integrated Multi-Omics for Novel Aging Biomarkers and Antiaging Targets Biomolecules 12 1 https://www.doi.org/10./biom 35,053,186 Aging/genetics Biomarkers *Genomics/methods Humans Metabolomics/methods *Proteomics/methods aging aging biomarkers aging clock antiaging targets multi-omics Aging is closely related to the occurrence of human diseases; however, its exact biological mechanism is unclear. Advancements in high-throughput technology provide new opportunities for omics research to understand the pathological process of various complex human diseases. However, single-omics technologies only provide limited insights into the biological mechanisms of diseases. DNA, RNA, protein, metabolites, and microorganisms usually play complementary roles and perform certain biological functions together. In this review, we summarize multi-omics methods based on the most relevant biomarkers in single-omics to better understand molecular functions and disease causes. The integration of multi-omics technologies can systematically reveal the interactions among aging molecules from a multidimensional perspective. Our review provides new insights regarding the discovery of aging biomarkers, mechanism of aging, and identification of novel antiaging targets. Overall, data from genomics, transcriptomics, proteomics, metabolomics, integromics, microbiomics, and systems biology contribute to the identification of new candidate biomarkers for aging and novel targets for antiaging interventions. Wu, Lei Xie, Xinqiang Liang, Tingting Ma, Jun Yang, Lingshuang Yang, Juan Li, Longyan Xi, Yu Li, Haixin Zhang, Jumei Chen, Xuefeng Ding, Yu Wu, Qingping eng Research Support, Non-U.S. Gov't Review Switzerland Biomolecules. Dec 28;12(1):39. doi: 10./biom.I SomaScan 01/22/ Wu J, et al. Multi-omic analysis in injured humans: Patterns align with outcomes and treatment responses Cell Rep Med 2 12 https://www.doi.org/10./j.xcrm.. 35,028,617 Brain Injuries, Traumatic/*genetics/*therapy Cluster Analysis Cohort Studies *Genomics Humans Metabolome Plasma Proteome/metabolism Time Factors Treatment Outcome PAMPer trial endotype host response metabolomics multi-omics outcome proteomics systemic storm thawed plasma trauma Avita Medical and Spectral MD. M.D.N. holds an equity stake in Haima Therapeutics. He has received research support and/or honoraria from Haemonetics, Instrumentation Laboratories, and Janssen Pharmaceuticals. T.R.B. is a stakeholder in Immunetrics. Other authors declare no conflict of interests. Trauma is a leading cause of death and morbidity worldwide. Here, we present the analysis of a longitudinal multi-omic dataset comprising clinical, cytokine, endotheliopathy biomarker, lipidome, metabolome, and proteome data from severely injured humans. A systemic storm" pattern with release of 1,061 markers, together with a pattern suggestive of the "massive consumption" of 892 constitutive circulating markers, is identified in the acute phase post-trauma. Data integration reveals two human injury response endotypes, which align with clinical trajectory. Prehospital thawed plasma rescues only endotype 2 patients with traumatic brain injury (30-day mortality: 30.3 versus 75.0%; p = 0.). Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) was identified as the most predictive circulating biomarker to identify endotype 2-traumatic brain injury (TBI) patients. These response patterns refine the paradigm for human injury, while the datasets provide a resource for the study of critical illness, trauma, and human stress responses." Wu, Junru Vodovotz, Yoram Abdelhamid, Sultan Guyette, Francis X Yaffe, Michael B Gruen, Danielle S Cyr, Anthony Okonkwo, David O Kar, Upendra K Krishnamoorthi, Neha Voinchet, Robert G Billiar, Isabel M Yazer, Mark H Namas, Rami A Daley, Brian J Miller, Richard S Harbrecht, Brian G Claridge, Jeffrey A Phelan, Herbert A Zuckerbraun, Brian S Johansson, Par I Stensballe, Jakob Morrissey, James H Tracy, Russell P Wisniewski, Stephen R Neal, Matthew D Sperry, Jason L Billiar, Timothy R eng T32 GM/GM/NIGMS NIH HHS/ UM1 HL/HL/NHLBI NIH HHS/ R35 GM/GM/NIGMS NIH HHS/ R35 GM/GM/NIGMS NIH HHS/ R01 HL/HL/NHLBI NIH HHS/ Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Cell Rep Med. Dec 21;2(12):. doi: 10./j.xcrm... eCollection Dec 21.I SomaScan 01/15/ Ghodsian N, et al. Blood Levels of the SMOC1 Hepatokine Are Not Causally Linked with Type 2 Diabetes: A Bidirectional Mendelian Randomization Study Nutrients 13 12 https://www.doi.org/10./nu 34,959,760 Blood Glucose/metabolism Body Mass Index Case-Control Studies Diabetes Mellitus, Type 2/blood/*genetics Fasting/blood Gene Expression/physiology Genome-Wide Association Study Glycated Hemoglobin A/metabolism Humans Insulin/blood Insulin Resistance/genetics Liver/metabolism Mendelian Randomization Analysis Non-alcoholic Fatty Liver Disease/blood/*genetics Osteonectin/*blood Polymorphism, Single Nucleotide Risk Factors Waist-Hip Ratio Mendelian randomization Smoc1 hepatokine type 2 diabetes research contracts from Pfizer, Ionis Pharmaceuticals and Silence Therapeutics. Hepatokines are liver-derived proteins that may influence metabolic pathways such as insulin sensitivity. Recently, Sparc-related modular calcium-binding protein 1 (SMOC1) was identified as glucose-responsive hepatokine that is dysregulated in the setting of non-alcoholic fatty liver disease (NAFLD). While SMOC1 may influence glucose-insulin homeostasis in rodents, it is unknown if SMOC1 is influenced by NAFLD in humans. It is also unknown if SMOC1 is causally associated with metabolic and disease traits in humans. Therefore, we aimed to determine the effect of NAFLD on SMOC1 gene expression in the liver and aimed to explore the potential causal associations of SMOC1 levels with NAFLD, T2D, and glycemic traits in humans. Using an RNA sequencing dataset from a cohort of 216 patients with NAFLD, we assessed SMOC1 expression levels across the NAFLD spectrum. We performed a series of bidirectional inverse-variance weighted Mendelian randomization (MR) analyses on blood SMOC1 levels using two sources of genome-wide association studies (GWAS) (Fenland study, n = 10,708 and INTERVAL study, n = ). We utilized GWAS summary statistics for NAFLD in cases and 770,180 controls, as well as publicly available GWAS for type 2 diabetes (T2D), body mass index (BMI), waist-to-hip ratio (WHR), fasting blood insulin (FBI), fasting blood glucose (FBG), homeostatic Model Assessment of Insulin Resistance (HOMA-B and HOMA-IR), and hemoglobin A1c (HbA1C). We found that SMOC1 expression showed no significant differences across NAFLD stages. We also identified that the top single-nucleotide polymorphism associated with blood SMOC1 levels, was associated with SMOC1 gene expression in the liver, but not in other tissues. Using MR, we did not find any evidence that genetically predicted NAFLD, T2D, and glycemic traits influenced SMOC1 levels. We also did not find evidence that blood SMOC1 levels were causally associated with T2D, NAFLD, and glycemic traits. In conclusion, the hepatokine SMOC1 does not appear to be modulated by the presence of NAFLD and may not regulate glucose-insulin homeostasis in humans. Results of this study suggest that blood factors regulating metabolism in rodents may not always translate to human biology. Ghodsian, Nooshin Gagnon, Eloi Bourgault, Jerome Gobeil, Emilie Manikpurage, Hasanga D Perrot, Nicolas Girard, Arnaud Mitchell, Patricia L Arsenault, Benoit J eng Switzerland Nutrients. Nov 24;13(12):. doi: 10./nu.I SomaScan 12/29/ Suzuki M, et al. Large-scale plasma proteomics can reveal distinct endotypes in chronic obstructive pulmonary disease and severe asthma Clin Transl Allergy 11 10 e https://www.doi.org/10./clt2. 34,962,717 Bpco Copd Epoc asma severa asthme severe endotipos endotypen endotypes exosomas exosome exosomen exosomes proteomic proteomics proteomica proteomique schweres Asthma severe asthma ______ ______ _______ ____ Masaru Suzuki has received lecture fees from AstraZeneca, Boehringer Ingelheim, Novartis, and GlaxoSmithKline. Satoshi Konno has received grants from AstraZeneca, Boehringer Ingelheim, KYORIN Pharmaceutical, Novartis, and Japan Allergy Foundation during the conduct of the study, and has received lecture fees from AstraZeneca and Boehringer Ingelheim. Masaharu Nishimura has received grants from AstraZeneca, Boehringer Ingelheim, KYORIN Pharmaceutical, and MSD during the conduct of the study. John J. Cole, Hironi Makita, and Hiroki Kimura have no relevant conflicts of interest. BACKGROUND: Chronic airway diseases including chronic obstructive pulmonary disease (COPD) and asthma are heterogenous in nature and endotypes within are underpinned by complex biology. This study aimed to investigate the utility of proteomic profiling of plasma combined with bioinformatic mining, and to define molecular endotypes and expand our knowledge of the underlying biology in chronic respiratory diseases. METHODS: The plasma proteome was evaluated using an aptamer-based affinity proteomics platform (SOMAscan(R)), representing proteins in 34 subjects with stable COPD and 51 subjects with stable but severe asthma. For each disease, we evaluated a range of clinical/demographic characteristics including bronchodilator reversibility, blood eosinophilia levels, and smoking history. We applied modified bioinformatic approaches used in the evaluation of RNA transcriptomics. RESULTS: Subjects with COPD and severe asthma were distinguished from each other by 365 different protein abundancies, with differential pathway networks and upstream modulators. Furthermore, molecular endotypes within each disease could be defined. The protein groups that defined these endotypes had both known and novel biology including groups significantly enriched in exosomal markers derived from immune/inflammatory cells. Finally, we observed associations to clinical characteristics that previously have been under-explored. CONCLUSION: This investigational study evaluating the plasma proteome in clinically-phenotyped subjects with chronic airway diseases provides support that such a method can be used to define molecular endotypes and pathobiological mechanisms that underpins these endotypes. It provided new concepts about the complexity of molecular pathways that define these diseases. In the longer term, such information will help to refine treatment options for defined groups. Suzuki, Masaru Cole, John J Konno, Satoshi Makita, Hironi Kimura, Hiroki Nishimura, Masaharu Maciewicz, Rose A eng KYORIN Pharmaceutical/ Pfizer/ Boehringer Ingelheim/ Ministry of Health, Labor, and Welfare, Japan/ AstraZeneca/ Japan Allergy Foundation/ /Ministry of Education, Science, Culture and Sports of Japan/ /Ministry of Education, Science, Culture and Sports of Japan/ /Ministry of Education, Science, Culture and Sports of Japan/ England Clin Transl Allergy. Dec;11(10):e. doi: 10./clt2..I SomaScan 12/29/ Daniels JR, et al. Discovery of Novel Proteomic Biomarkers for the Prediction of Kidney Recovery from Dialysis-Dependent AKI Patients Kidney360 2 11 - https://www.doi.org/10./kid. 34,913,041 *Acute Kidney Injury/diagnosis Biomarkers/urine Humans Kidney/metabolism *Proteomics Renal Dialysis/methods BACKGROUND: AKI requiring dialysis (AKI-D) is associated with prolonged hospitalization, mortality, and progressive CKD among survivors. Previous studies have examined only select urine or serum biomarkers for predicting kidney recovery from AKI. METHODS: Serum samples collected on day 8 of randomized RRT from 72 patients enrolled in the Veteran's Affairs/National Institutes of Health Acute Renal Failure Trial Network study were analyzed by the SOMAscan proteomic platform to profile proteins in each sample. Of these patients, 38 recovered kidney function and dialysis was discontinued, whereas another 34 patients remained on dialysis by day 28. RESULTS: Differential serum levels of 119 proteins, with 53 higher and 66 lower, were detected in samples from patients who discontinued dialysis, compared with patients who remained on dialysis by day 28. Patients were classified into tertiles on the basis of SOMAscan protein measurements for the 25 proteins most differentially expressed. The association of serum levels of each protein with kidney recovery was further evaluated using logistic regression analysis. Higher serum levels of CXCL11, CXCL2/CXCL3, CD86, Wnt-7a, BTK, c-Myc, TIMP-3, CCL5, ghrelin, PDGF-C, survivin, CA2, IL-9, EGF, and neuregulin-1, and lower levels of soluble CXCL16, IL1RL1, stanniocalcin-1, IL-6, and FGF23 when classified in tertiles were significantly associated with better kidney recovery. This significant association persisted for each of these proteins after adjusting for potential confounding risk factors including age, sex, cardiovascular SOFA score, congestive heart failure, diabetes, modality of intensive dialysis treatment, cause of AKI, baseline serum creatinine, day 8 urine volume, and estimated 60-day mortality risk. CONCLUSIONS: These results suggest concerted changes between survival-related proteins and immune-regulatory chemokines in regulating angiogenesis, endothelial and epithelial remodeling, and kidney cell regeneration, illustrating potential mechanisms of kidney recovery. Thus, this study identifies potential novel predictive biomarkers of kidney recovery in patients with AKI-D. Daniels, Jaclyn R Ma, Jennie Z Cao, Zhijun Beger, Richard D Sun, Jinchun Schnackenberg, Laura Pence, Lisa Choudhury, Devasmita Palevsky, Paul M Portilla, Didier Yu, Li-Rong eng FD/ImFDA/Intramural FDA HHS/ R01 DK/DK/NIDDK NIH HHS/ R01 DK/DK/NIDDK NIH HHS/ Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Kidney360. Nov 25;2(11):-. doi: 10./kid..I SomaScan 12/17/ Sayed N, et al. An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging Nat Aging 1 598-615 https://www.doi.org/10./s-021--y 34,888,528 While many diseases of aging have been linked to the immunological system, immune metrics capable of identifying the most at-risk individuals are lacking. From the blood immunome of 1,001 individuals aged 8-96 years, we developed a deep-learning method based on patterns of systemic age-related inflammation. The resulting inflammatory clock of aging (iAge) tracked with multimorbidity, immunosenescence, frailty and cardiovascular aging, and is also associated with exceptional longevity in centenarians. The strongest contributor to iAge was the chemokine CXCL9, which was involved in cardiac aging, adverse cardiac remodeling and poor vascular function. Furthermore, aging endothelial cells in human and mice show loss of function, cellular senescence and hallmark phenotypes of arterial stiffness, all of which are reversed by silencing CXCL9. In conclusion, we identify a key role of CXCL9 in age-related chronic inflammation and derive a metric for multimorbidity that can be utilized for the early detection of age-related clinical phenotypes. Sayed, Nazish Huang, Yingxiang Nguyen, Khiem Krejciova-Rajaniemi, Zuzana Grawe, Anissa P Gao, Tianxiang Tibshirani, Robert Hastie, Trevor Alpert, Ayelet Cui, Lu Kuznetsova, Tatiana Rosenberg-Hasson, Yael Ostan, Rita Monti, Daniela Lehallier, Benoit Shen-Orr, Shai S Maecker, Holden T Dekker, Cornelia L Wyss-Coray, Tony Franceschi, Claudio Jojic, Vladimir Haddad, Francois Montoya, Jose G Wu, Joseph C Davis, Mark M Furman, David eng P30 AG/AG/NIA NIH HHS/ P30 AG/AG/NIA NIH HHS/ U19 AI/AI/NIAID NIH HHS/ U19 AI/AI/NIAID NIH HHS/ P50 AG/AG/NIA NIH HHS/ P30 DK/DK/NIDDK NIH HHS/ UL1 TR/TR/NCATS NIH HHS/ UL1 RR/RR/NCRR NIH HHS/ K01 HL/HL/NHLBI NIH HHS/ Nat Aging. Jul;1:598-615. doi: 10./s-021--y. Epub Jul 12.I SomaScan 12/11/ De Miguel Z, et al. Exercise plasma boosts memory and dampens brain inflammation via clusterin Nature 600 7,889 494-499 https://www.doi.org/10./s-021--x 34,880,498 *Alzheimer Disease/metabolism Animals Clusterin/genetics/metabolism *Encephalitis Endothelial Cells/metabolism Humans Mice Proteomics Physical exercise is generally beneficial to all aspects of human and animal health, slowing cognitive ageing and neurodegeneration(1). The cognitive benefits of physical exercise are tied to an increased plasticity and reduced inflammation within the hippocampus(2-4), yet little is known about the factors and mechanisms that mediate these effects. Here we show that 'runner plasma', collected from voluntarily running mice and infused into sedentary mice, reduces baseline neuroinflammatory gene expression and experimentally induced brain inflammation. Plasma proteomic analysis revealed a concerted increase in complement cascade inhibitors including clusterin (CLU). Intravenously injected CLU binds to brain endothelial cells and reduces neuroinflammatory gene expression in a mouse model of acute brain inflammation and a mouse model of Alzheimer's disease. Patients with cognitive impairment who participated in structured exercise for 6 months had higher plasma levels of CLU. These findings demonstrate the existence of anti-inflammatory exercise factors that are transferrable, target the cerebrovasculature and benefit the brain, and are present in humans who engage in exercise. De Miguel, Zurine Khoury, Nathalie Betley, Michael J Lehallier, Benoit Willoughby, Drew Olsson, Niclas Yang, Andrew C Hahn, Oliver Lu, Nannan Vest, Ryan T Bonanno, Liana N Yerra, Lakshmi Zhang, Lichao Saw, Nay Lui Fairchild, J Kaci Lee, Davis Zhang, Hui McAlpine, Patrick L Contrepois, Kevin Shamloo, Mehrdad Elias, Joshua E Rando, Thomas A Wyss-Coray, Tony eng R01 AG/AG/NIA NIH HHS/ P30 AG/AG/NIA NIH HHS/ F32 AG/AG/NIA NIH HHS/ R01 AG/AG/NIA NIH HHS/ P01 AG/AG/NIA NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. England Nature. Dec;600():494-499. doi: 10./s-021--x. Epub Dec 8.I SomaScan 12/10/ O'Neil LJ, et al. Proteomic Approaches to Defining Remission and the Risk of Relapse in Rheumatoid Arthritis Front Immunol 12 https://www.doi.org/10./fimmu.. 34,867,950 Adult Aged Antirheumatic Agents/therapeutic use Arthritis, Rheumatoid/*blood/*classification/drug therapy Biomarkers/blood Blood Proteins/*analysis Female Humans Male Middle Aged Proteomics Recurrence Remission Induction disease activity outcomes research rheumatoid arthritis treatment commercial or financial relationships that could be construed as a potential conflict of interest. OBJECTIVES: Patients with Rheumatoid Arthritis (RA) are increasingly achieving stable disease remission, yet the mechanisms that govern ongoing clinical disease and subsequent risk of future flare are not well understood. We sought to identify serum proteomic alterations that dictate clinically important features of stable RA, and couple broad-based proteomics with machine learning to predict future flare. METHODS: We studied baseline serum samples from a cohort of stable RA patients (RETRO, n = 130) in clinical remission (DAS28/= +/- 1.5, false discovery ratio (FDR) = 0.1) in IPF samples compared to healthy controls. IPF samples showed strong enrichment of chemotaxis, tumor infiltration and mast cell migration pathways and downregulated extracellular matrix (ECM) degradation. Mucosal (CCL25 and CCL28) and Th2 (CCL17 and CCL22) chemokines were markedly upregulated in IPF and highly correlated within the subjects. The mast cell maturation chemokine, CXCL12, was also upregulated in IPF plasma (fold change 1.92, FDR 0.006) and significantly correlated (Pearson r = - 0.38, p = 0.022) to lung function (%predicted FVC), with a concomitant increase in the mast cell Tryptase, TPSB2. Markers of collagen III and VI degradation (C3M and C6M) were significantly downregulated (C3M p 75% of primary brain tumors. This includes anaplastic astrocytoma (grade III; AS), the most common and fatal glioblastoma multiforme (grade IV; GBM), and oligodendroglioma (ODG). We have generated patient-derived AS, GBM, and ODG cell models to study disease mechanisms and test patient-centered therapeutic strategies. We have used an aptamer-based high-throughput SOMAscan((R)) 1.3K assay to determine the proteomic profiles of different analytes. SOMAscan((R)) proteomes of AS and GBM self-organized into closely adjacent proteomes which were clearly distinct from ODG proteomes. GBM self-organized into four proteomic clusters of which SOMAscan((R)) cluster 4 proteome predicted a highly inter-connected proteomic network. Several up- and down-regulated proteins relevant to glioma were successfully validated in GBM cell isolates across different SOMAscan((R)) clusters and in corresponding GBM tissues. Slow off-rate modified aptamer proteomics is an attractive analytical tool for rapid proteomic stratification of different malignant gliomas and identified cluster-specific SOMAscan((R)) signatures and functionalities in patient GBM cells. Thanasupawat, Thatchawan Glogowska, Aleksandra Pascoe, Christopher Krishnan, Sai Nivedita Munir, Maliha Begum, Farhana Beiko, Jason Krcek, Jerry Del Bigio, Marc R Pitz, Marshall Shen, Yaoqing Spicer, Victor Coombs, Kevin M Wilkins, John Hombach-Klonisch, Sabine Klonisch, Thomas eng Switzerland Int J Mol Sci. Sep 3;22(17):. doi: 10./ijms.I SomaScan 09/11/ Ren X, et al. Evolving A RIG-I Antagonist: A Modified DNA Aptamer Mimics Viral RNA J Mol Biol 433 21 https://www.doi.org/10./j.jmb.. 34,487,794 Antigens, Viral/*chemistry/metabolism Aptamers, Nucleotide/*chemistry/metabolism Binding Sites Cloning, Molecular Crystallography, X-Ray DEAD Box Protein 58/*chemistry/genetics/metabolism Escherichia coli/genetics/metabolism Gene Expression Genetic Vectors/chemistry/metabolism Humans Immunologic Factors/*chemistry/metabolism Kinetics Models, Molecular Molecular Mimicry Mutation Nucleic Acid Conformation Protein Binding Protein Conformation, alpha-Helical Protein Conformation, beta-Strand Protein Interaction Domains and Motifs RNA, Viral/*chemistry/metabolism Receptors, Immunologic/*chemistry/genetics/metabolism Recombinant Proteins/chemistry/genetics/metabolism SELEX Aptamer Technique DNA structure in-vitro innate immunity molecular recognition nucleic acid folding Vertebrate organisms express a diversity of protein receptors that recognize and respond to the presence of pathogenic molecules, functioning as an early warning system for infection. As a result of mutation or dysregulated metabolism, these same innate immune receptors can be inappropriately activated, leading to inflammation and disease. One of the most important receptors for detection and response to RNA viruses is called RIG-I, and dysregulation of this protein is linked with a variety of disease states. Despite its central role in inflammatory responses, antagonists for RIG-I are underdeveloped. In this study, we use invitro selection from a pool of modified DNA aptamers to create a high affinity RIG-I antagonist. A high resolution crystal structure of the complex reveals molecular mimicry between the aptamer and the 5'-triphosphate terminus of viral ligands, which bind to the same amino acids within the CTD recognition platform of the RIG-I receptor. Our study suggests a powerful, generalizable strategy for generating immunomodulatory drugs and mechanistic tool compounds. Ren, Xiaoming Gelinas, Amy D Linehan, Melissa Iwasaki, Akiko Wang, Wenshuai Janjic, Nebojsa Pyle, Anna Marie eng Research Support, Non-U.S. Gov't Netherlands J Mol Biol. Oct 15;433(21):. doi: 10./j.jmb... Epub Sep 3.I SomaScan 09/07/ Berry J, et al. Radicava/Edaravone Findings in Biomarkers From Amyotrophic Lateral Sclerosis (REFINE-ALS): Protocol and Study Design Neurol Clin Pract 11 4 e472-e479 https://www.doi.org/10./CPJ. 34,476,128 OBJECTIVES: To identify putative biomarkers that may serve as quantifiable, biological, nonclinical measures of the pharmacodynamic effect of edaravone in amyotrophic lateral sclerosis (ALS) and to report real-world treatment outcomes. METHODS: This is a prospective, observational, longitudinal, multicenter (up to 40 sites) US study (Clinicaltrials.gov; NCT) with at least 200 patients with ALS who will receive edaravone for 24 weeks (6 cycles; Food and Drug Administration-approved regimen). All participants must either be treatment naive for edaravone or be more than 1 month without receiving any edaravone dose before screening. Biomarker quantification and other assessments will be performed at baseline (before cycle 1) and during cycles 1, 3, and 6. Selected biomarkers of oxidative stress, inflammation, neuronal injury and death, and muscle injury, as well as biomarker discovery panels (EpiSwitch and SOMAscan), will be evaluated and, when feasible, compared with biobanked samples. Clinical efficacy assessments will include the ALS Functional Rating Scale-Revised, King's clinical staging, ALS Assessment Questionnaire-40, Appel ALS Score (Rating Scale), slow vital capacity, hand-held dynamometry and grip strength, and time to specified states of disease progression or death. DNA samples will also be collected for potential genomic evaluation. The predicted rates of progression and survival, and their potential correlations with biomarkers, will be evaluated. Adverse events related to the study will be reported. RESULTS: The study is estimated to be completed in with an interim analysis planned. CONCLUSIONS: Findings may help to further the understanding of the pharmacodynamic effect of edaravone, including changes in biomarkers, in response to treatment. Berry, James Brooks, Benjamin Genge, Angela Heiman-Patterson, Terry Appel, Stanley Benatar, Michael Bowser, Robert Cudkowicz, Merit Gooch, Clifton Shefner, Jeremy Westra, Jurjen Agnese, Wendy Merrill, Charlotte Nelson, Sally Apple, Stephen eng Neurol Clin Pract. Aug;11(4):e472-e479. doi: 10./CPJ..I SomaScan 09/04/ Rhee J, et al. Serum Proteomics of Older Patients Undergoing Major Cardiac Surgery: Identification of Biomarkers Associated With Postoperative Delirium Front Aging Neurosci 13 https://www.doi.org/10./fnagi.. 34,456,709 Il-6 Pde3a SOMAscan Timp-1 TruCulture cardiopulmonary bypass postoperative delirium proteomics commercial or financial relationships that could be construed as a potential conflict of interest. BACKGROUND: Postoperative delirium (POD) is an acute altered mental state commonly encountered after cardiac surgery. The pathophysiological mechanisms underlying POD remain unclear. We aimed to identify circulating proteins significantly altered after major cardiac surgery with cardiopulmonary bypass (CPB). We also aimed to enable inferences on associations with POD. METHODS: Serum and whole blood samples were collected before CPB (n = 16 patients; n = 8 with POD) and again from the same patients on postoperative day 1. All patients were clinically evaluated for POD on postoperative days 1-3. An aptamer-based proteomics platform (SOMAscan) was used to quantify serum protein abundance in patients with POD compared with non-POD controls. We also performed a lipopolysaccharide (LPS)-based in vitro functional analysis (TruCulture) on whole blood samples from patients with POD and non-POD controls to approximate surgical stress. Cytokine levels were determined using a Luminex immunoassay. RESULTS: Cardiac surgery with CPB resulted in a significant (p(adj) 0.97; PP explained by the candidate variant [PP(explained)] = 1) that was independent from a cluster of CAD and lipid traits driven by a known missense variant in APOE (rs; distance to E354 approximately 770 Kb; R (2) with E354 = 0.004; PP(coloc) > 0.99; PP(explained) = 1). Further, conditioning the association between E354 and CAD on the residual LD with rs, we observed slight attenuation in association, but it remained significant (odds ratio [OR] per copy of E354 after adjustment 1.03; 95% CI 1.02, 1.04; P = 0.003). Instead, E354's association with CAD was completely attenuated when conditioning on an additional established CAD signal, rs (R (2) with E354 = 0.27), an intronic variant in SNRPD2 (OR for E354 after adjustment for rs: 1.01; 95% CI 0.99, 1.03; P = 0.06). We demonstrate that associations with GIP and anthropometric and glycemic traits are driven by genetic signals distinct from those driving CAD and lipid traits in the GIPR region and that higher E354-mediated fasting GIP levels are not associated with CAD risk. These findings provide evidence that the inclusion of GIPR agonism in dual GIPR/GLP1R agonists could potentiate the protective effect of GLP-1 agonists on diabetes without undue CAD risk, an aspect that has yet to be assessed in clinical trials. Bowker, Nicholas Hansford, Robert Burgess, Stephen Foley, Christopher N Auyeung, Victoria P W Erzurumluoglu, A Mesut Stewart, Isobel D Wheeler, Eleanor Pietzner, Maik Gribble, Fiona Reimann, Frank Bhatnagar, Pallav Coghlan, Matthew P Wareham, Nicholas J Langenberg, Claudia eng MC_UU_/3/MRC_/Medical Research Council/United Kingdom DH_/Department of Health/United Kingdom C864/A/CRUK_/Cancer Research UK/United Kingdom MC_PC_/MRC_/Medical Research Council/United Kingdom G/MRC_/Medical Research Council/United Kingdom /Z/14/Z/WT_/Wellcome Trust/United Kingdom G/MRC_/Medical Research Council/United Kingdom /CRUK_/Cancer Research UK/United Kingdom WT_/Wellcome Trust/United Kingdom MC_UU_/1/MRC_/Medical Research Council/United Kingdom MC_UU_/3/MRC_/Medical Research Council/United Kingdom /Z/14/Z/WT_/Wellcome Trust/United Kingdom MR/N/1/MRC_/Medical Research Council/United Kingdom MC_UU_/1/MRC_/Medical Research Council/United Kingdom MC_PC_/MRC_/Medical Research Council/United Kingdom Research Support, Non-U.S. Gov't Diabetes. Nov;70(11):-. doi: 10./db21-. Epub Aug 23.I SomaScan 08/25/ Snider JM, et al. Group IIA secreted phospholipase A2 is associated with the pathobiology leading to COVID-19 mortality J Clin Invest 131 19 https://www.doi.org/10./JCI 34,428,181 Adolescent Adult Aged Aged, 80 and over COVID-19/*blood/*mortality Child Disease-Free Survival Female Group II Phospholipases A2/*blood Humans Male Middle Aged SARS-CoV-2/*metabolism Severity of Illness Index Survival Rate Covid-19 Cellular immune response Inflammation Molecular pathology officer of MicroRid Technologies Inc. There is an urgent need to identify the cellular and molecular mechanisms responsible for severe COVID-19 that results in death. We initially performed both untargeted and targeted lipidomics as well as focused biochemical analyses of 127 plasma samples and found elevated metabolites associated with secreted phospholipase A2 (sPLA2) activity and mitochondrial dysfunction in patients with severe COVID-19. Deceased COVID-19 patients had higher levels of circulating, catalytically active sPLA2 group IIA (sPLA2-IIA), with a median value that was 9.6-fold higher than that for patients with mild disease and 5.0-fold higher than the median value for survivors of severe COVID-19. Elevated sPLA2-IIA levels paralleled several indices of COVID-19 disease severity (e.g., kidney dysfunction, hypoxia, multiple organ dysfunction). A decision tree generated by machine learning identified sPLA2-IIA levels as a central node in the stratification of patients who died from COVID-19. Random forest analysis and least absolute shrinkage and selection operator-based (LASSO-based) regression analysis additionally identified sPLA2-IIA and blood urea nitrogen (BUN) as the key variables among 80 clinical indices in predicting COVID-19 mortality. The combined PLA-BUN index performed significantly better than did either one alone. An independent cohort (n = 154) confirmed higher plasma sPLA2-IIA levels in deceased patients compared with levels in plasma from patients with severe or mild COVID-19, with the PLA-BUN index-based decision tree satisfactorily stratifying patients with mild, severe, or fatal COVID-19. With clinically tested inhibitors available, this study identifies sPLA2-IIA as a therapeutic target to reduce COVID-19 mortality. Snider, Justin M You, Jeehyun Karen Wang, Xia Snider, Ashley J Hallmark, Brian Zec, Manja M Seeds, Michael C Sergeant, Susan Johnstone, Laurel Wang, Qiuming Sprissler, Ryan Carr, Tara F Lutrick, Karen Parthasarathy, Sairam Bime, Christian Zhang, Hao Helen Luberto, Chiara Kew, Richard R Hannun, Yusuf A Guerra, Stefano McCall, Charles E Yao, Guang Del Poeta, Maurizio Chilton, Floyd H eng I01 BX/BX/BLRD VA/ P30 ES/ES/NIEHS NIH HHS/ R01 AI/AI/NIAID NIH HHS/ P01 CA/CA/NCI NIH HHS/ UL1 TR/TR/NCATS NIH HHS/ R01 AI/AI/NIAID NIH HHS/ Clinical Trial Multicenter Study Observational Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't J Clin Invest. Oct 1;131(19):e. doi: 10./JCI.I SomaScan 08/25/ Kivimaki M, et al. Cognitive stimulation in the workplace, plasma proteins, and risk of dementia: three analyses of population cohort studies BMJ 374 n https://www.doi.org/10./bmj.n 34,407,988 Aged Aged, 80 and over Blood Proteins/analysis Dementia/blood/*epidemiology Europe/epidemiology Female Humans Incidence Male Neuropsychological Tests Occupational Diseases/blood/*epidemiology/psychology Occupations/*statistics & numerical data Proportional Hazards Models Prospective Studies Risk Factors Sedentary Behavior United Kingdom/epidemiology United States/epidemiology Workplace/*psychology OBJECTIVES: To examine the association between cognitively stimulating work and subsequent risk of dementia and to identify protein pathways for this association. DESIGN: Multicohort study with three sets of analyses. SETTING: United Kingdom, Europe, and the United States. PARTICIPANTS: Three associations were examined: cognitive stimulation and dementia risk in 107 896 participants from seven population based prospective cohort studies from the IPD-Work consortium (individual participant data meta-analysis in working populations); cognitive stimulation and proteins in a random sample of participants from one cohort study; and proteins and dementia risk in 13 656 participants from two cohort studies. MAIN OUTCOME MEASURES: Cognitive stimulation was measured at baseline using standard questionnaire instruments on active versus passive jobs and at baseline and over time using a job exposure matrix indicator. proteins in plasma samples were scanned. Follow-up of incident dementia varied between 13.7 to 30.1 years depending on the cohort. People with dementia were identified through linked electronic health records and repeated clinical examinations. RESULTS: During 1.8 million person years at risk, people with dementia were recorded. The risk of dementia was found to be lower for participants with high compared with low cognitive stimulation at work (crude incidence of dementia per 10 000 person years 4.8 in the high stimulation group and 7.3 in the low stimulation group, age and sex adjusted hazard ratio 0.77, 95% confidence interval 0.65 to 0.92, heterogeneity in cohort specific estimates I(2)=0%, P=0.99). This association was robust to additional adjustment for education, risk factors for dementia in adulthood (smoking, heavy alcohol consumption, physical inactivity, job strain, obesity, hypertension, and prevalent diabetes at baseline), and cardiometabolic diseases (diabetes, coronary heart disease, stroke) before dementia diagnosis (fully adjusted hazard ratio 0.82, 95% confidence interval 0.68 to 0.98). The risk of dementia was also observed during the first 10 years of follow-up (hazard ratio 0.60, 95% confidence interval 0.37 to 0.95) and from year 10 onwards (0.79, 0.66 to 0.95) and replicated using a repeated job exposure matrix indicator of cognitive stimulation (hazard ratio per 1 standard deviation increase 0.77, 95% confidence interval 0.69 to 0.86). In analysis controlling for multiple testing, higher cognitive stimulation at work was associated with lower levels of proteins that inhibit central nervous system axonogenesis and synaptogenesis: slit homologue 2 (SLIT2, fully adjusted beta -0.34, P0.9, p=1 x 10(-4)), implicating Fas-mediated apoptosis as a potential target for COVID-19 risk. The polygenic (pan) and cis-Mendelian randomisation analyses showed consistent associations of genetically predicted ABO protein with several COVID-19 phenotypes. The ABO signal is highly pleiotropic, and a look-up of proteins associated with the ABO signal revealed that the strongest association was with soluble CD209. We demonstrated experimentally that CD209 directly interacts with the spike protein of SARS-CoV-2, suggesting a mechanism that could explain the ABO association with COVID-19. CONCLUSIONS: Our work provides a prioritised list of host targets potentially exploited by SARS-CoV-2 and is a precursor for further research on CD209 and FAS as therapeutically tractable targets for COVID-19. FUNDING: MAK, JSc, JH, AB, DO, MC, EMM, MG, ID were funded by Open Targets. J.Z. and T.R.G were funded by the UK Medical Research Council Integrative Epidemiology Unit (MC_UU_/4). JSh and GJW were funded by the Wellcome Trust Grant . This research was funded in part by the Wellcome Trust [Grant ]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. Individuals who become infected with the virus that causes COVID-19 can experience a wide variety of symptoms. These can range from no symptoms or minor symptoms to severe illness and death. Key demographic factors, such as age, gender and race, are known to affect how susceptible an individual is to infection. However, molecular factors, such as unique gene mutations and gene expression levels can also have a major impact on patient responses by affecting the levels of proteins in the body. Proteins that are too abundant or too scarce may mean the difference between dying from or surviving COVID-19. Identifying the molecular factors in a host that affect how viruses can infect individuals, evade immune defences or trigger severe illness, could provide new ways to treat patients with COVID-19. Such factors are likely to remain constant, even when the virus mutates into new strains. Hence, insights would likely apply across all virus strains, including current strains, such as alpha and delta, and any new strains that may emerge in the future. Using such a 'natural experiment' approach, Karim et al. compared the genetic profiles of over 30,000 COVID-19 patients and a million healthy individuals. Nine proteins were found to have an impact on COVID-19 infection and disease severity. Four proteins were ranked as top priorities for potential treatment targets. One protein, called CD209 (also known as DC-SIGN), is involved in how the virus enters the host cells, and had one of the strongest associations with COVID-19. Two proteins, called IL-6R and FAS, were involved in the immune response and could be responsible for the immune over-activation often seen in severe COVID-19. Finally, one protein, called OAS1, formed part of the body's innate antiviral defence system and appeared to reduce susceptibility to COVID-19. Knowing more about the proteins that influence the severity of COVID-19 opens up new ways to predict, protect and treat patients who may have severe or fatal reactions to infection. Indeed, one of the identified proteins (IL-6R) had already been targeted in recent clinical trials with some encouraging results. Considering CD209 as a potential receptor for the virus could provide another avenue for therapeutics, similar to previously successful approaches to block the virus' known interaction with a receptor protein. Ultimately, this research could supply an entirely new set of treatment options to help combat the COVID-19 pandemic. eng Anisul, Mohd Shilts, Jarrod Schwartzentruber, Jeremy Hayhurst, James Buniello, Annalisa Shaikho Elhaj Mohammed, Elmutaz Zheng, Jie Holmes, Michael Ochoa, David Carmona, Miguel Maranville, Joseph Gaunt, Tom R Emilsson, Valur Gudnason, Vilmundur McDonagh, Ellen M Wright, Gavin J Ghoussaini, Maya Dunham, Ian eng Wellcome Trust/United Kingdom MC_UU_/4/MRC_/Medical Research Council/United Kingdom /WT_/Wellcome Trust/United Kingdom Research Support, Non-U.S. Gov't England Elife. Aug 17;10:e. doi: 10./eLife..I SomaScan 08/18/ Slieker RC, et al. Distinct Molecular Signatures of Clinical Clusters in People With Type 2 Diabetes: An IMI-RHAPSODY Study Diabetes 70 11 - https://www.doi.org/10./db20- 34,376,475 Cluster Analysis Cohort Studies Cross-Sectional Studies Diabetes Mellitus, Type 2/*metabolism Humans Insulin Resistance Type 2 diabetes is a multifactorial disease with multiple underlying aetiologies. To address this heterogeneity, investigators of a previous study clustered people with diabetes according to five diabetes subtypes. The aim of the current study is to investigate the etiology of these clusters by comparing their molecular signatures. In three independent cohorts, in total 15,940 individuals were clustered based on five clinical characteristics. In a subset, genetic (N = 12,828), metabolomic (N = 2,945), lipidomic (N = 2,593), and proteomic (N = 1,170) data were obtained in plasma. For each data type, each cluster was compared with the other four clusters as the reference. The insulin-resistant cluster showed the most distinct molecular signature, with higher branched-chain amino acid, diacylglycerol, and triacylglycerol levels and aberrant protein levels in plasma were enriched for proteins in the intracellular PI3K/Akt pathway. The obese cluster showed higher levels of cytokines. The mild diabetes cluster with high HDL showed the most beneficial molecular profile with effects opposite of those seen in the insulin-resistant cluster. This study shows that clustering people with type 2 diabetes can identify underlying molecular mechanisms related to pancreatic islets, liver, and adipose tissue metabolism. This provides novel biological insights into the diverse aetiological processes that would not be evident when type 2 diabetes is viewed as a homogeneous disease. Slieker, Roderick C Donnelly, Louise A Fitipaldi, Hugo Bouland, Gerard A Giordano, Giuseppe N Akerlund, Mikael Gerl, Mathias J Ahlqvist, Emma Ali, Ashfaq Dragan, Iulian Elders, Petra Festa, Andreas Hansen, Michael K van der Heijden, Amber A Mansour Aly, Dina Kim, Min Kuznetsov, Dmitry Mehl, Florence Klose, Christian Simons, Kai Pavo, Imre Pullen, Timothy J Suvitaival, Tommi Wretlind, Asger Rossing, Peter Lyssenko, Valeriya Legido Quigley, Cristina Groop, Leif Thorens, Bernard Franks, Paul W Ibberson, Mark Rutter, Guy A Beulens, Joline W J 't Hart, Leen M Pearson, Ewan R eng WT_/Wellcome Trust/United Kingdom /Z/13/Z/WT_/Wellcome Trust/United Kingdom WTAIA/WT_/Wellcome Trust/United Kingdom /Z/18/Z/WT_/Wellcome Trust/United Kingdom MR/R/1/MRC_/Medical Research Council/United Kingdom MR/J/1/MRC_/Medical Research Council/United Kingdom MR/L/1/MRC_/Medical Research Council/United Kingdom Research Support, Non-U.S. Gov't Diabetes. Nov;70(11):-. doi: 10./db20-. Epub Aug 10.I SomaScan 08/12/ Sullivan KD, et al. The COVIDome Explorer researcher portal Cell Rep 36 7 https://www.doi.org/10./j.celrep.. 34,348,131 Access to Information Adult COVID-19/*genetics/immunology/*metabolism Case-Control Studies Data Mining *Databases, Genetic Datasets as Topic Female Gene Expression Profiling Humans Male *Metabolome Metabolomics Middle Aged *Proteome Proteomics *Transcriptome Young Adult Covid-19 Crp Sars data portal immune system infection inflammation metabolism multi-omics serpins for Elly Lilly and has provided consulting services to Gilead Sciences Inc. J.M.E. also serves on the Cell Reports Advisory Board. The remaining authors declare no competing interests. COVID-19 pathology involves dysregulation of diverse molecular, cellular, and physiological processes. To expedite integrated and collaborative COVID-19 research, we completed multi-omics analysis of hospitalized COVID-19 patients, including matched analysis of the whole-blood transcriptome, plasma proteomics with two complementary platforms, cytokine profiling, plasma and red blood cell metabolomics, deep immune cell phenotyping by mass cytometry, and clinical data annotation. We refer to this multidimensional dataset as the COVIDome. We then created the COVIDome Explorer, an online researcher portal where the data can be analyzed and visualized in real time. We illustrate herein the use of the COVIDome dataset through a multi-omics analysis of biosignatures associated with C-reactive protein (CRP), an established marker of poor prognosis in COVID-19, revealing associations between CRP levels and damage-associated molecular patterns, depletion of protective serpins, and mitochondrial metabolism dysregulation. We expect that the COVIDome Explorer will rapidly accelerate data sharing, hypothesis testing, and discoveries worldwide. Sullivan, Kelly Daniel Galbraith, Matthew Dominic Kinning, Kohl Thomas Bartsch, Kyle William Levinsky, Nik Caldwell Araya, Paula Smith, Keith Patrick Granrath, Ross Erich Shaw, Jessica Rose Baxter, Ryan Michael Jordan, Kimberly Rae Russell, Seth Aaron Dzieciatkowska, Monika Ewa Reisz, Julie Ann Gamboni, Fabia Cendali, Francesca Isabelle Ghosh, Tusharkanti Monte, Andrew Albert Bennett, Tellen Demeke Miller, Michael George Hsieh, Elena Wen-Yuan D'Alessandro, Angelo Hansen, Kirk Charles Espinosa, Joaquin Maximiliano eng R01 HL/HL/NHLBI NIH HHS/ RM1 GM/GM/NIGMS NIH HHS/ P30 DK/DK/NIDDK NIH HHS/ R01 AI/AI/NIAID NIH HHS/ UL1 TR/TR/NCATS NIH HHS/ P30 CA/CA/NCI NIH HHS/ K23 AR/AR/NIAMS NIH HHS/ R35 GM/GM/NIGMS NIH HHS/ R01 HL/HL/NHLBI NIH HHS/ R21 HL/HL/NHLBI NIH HHS/ R01 HL/HL/NHLBI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Cell Rep. Aug 17;36(7):. doi: 10./j.celrep... Epub Jul 28.I SomaScan 08/05/ Liu RX, et al. Comparison of proteomic methods in evaluating biomarker-AKI associations in cardiac surgery patients Transl Res 238 49-62 https://www.doi.org/10./j.trsl..07.005 34,343,625 Acute Kidney Injury/*blood Aged Aged, 80 and over Aptamers, Peptide Biomarkers/*blood Blood Chemical Analysis/methods Blood Proteins/*analysis Cardiac Surgical Procedures/*adverse effects Female Humans Immunoassay/methods Male Middle Aged Preoperative Period Proteomics/*methods Although immunoassays are the most widely used protein measurement method, aptamer-based methods such as the SomaScan platform can quantify up to proteins per biosample, creating new opportunities for unbiased discovery. However, there is limited research comparing the consistency of biomarker-disease associations between immunoassay and aptamer-based platforms. In a substudy of the TRIBE-AKI cohort, preoperative and postoperative plasma samples from 294 patients with previous immunoassay measurements were analyzed using the SomaScan platform. Inter-platform Spearman correlations (r(s)) and biomarker-AKI associations were compared across 30 preoperative and 34 postoperative immunoassay-aptamer pairs. Possible factors contributing to inter-platform differences were examined including target protein characteristics, immunoassay, and SomaScan coefficients of variation, other assay characteristics, and sample storage time. The median r(s) was 0.54 (interquartile range [IQR] 0.34-0.83) in postoperative samples and 0.41 (IQR 0.21-0.69) in preoperative samples. We observed a trend of greater r(s) in biomarkers with greater concentrations; the Spearman correlation between the concentration of protein and the inter-platform correlation was 0.64 in preoperative pairs and 0.53 in postoperative pairs. Of proteins measured by immunoassays, we observed significant biomarker-AKI associations for 13 proteins preop and 24 postop; of all corresponding aptamers, 8 proteins preop and 12 postop. All proteins significantly associated with AKI as measured by SomaScan were also significantly associated with AKI as measured by immunoassay. All biomarker-AKI odds ratios were significantly different (P 0.50) inter-platform correlations. Although similar biomarker-disease associations were observed overall, biomarkers with high physiological concentrations tended to have the highest-confidence inter-platform operability in correlations and biomarker-disease associations. Aptamer assays provide excellent precision and an unprecedented coverage and promise for disease associations but interpretation of results should keep in mind a broad range of correlations with immunoassays. Liu, Richard X Thiessen-Philbrook, Heather R Vasan, Ramachandran S Coresh, Josef Ganz, Peter Bonventre, Joseph V Kimmel, Paul L Parikh, Chirag R eng R01 HL/HL/NHLBI NIH HHS/ HHSNC/HL/NHLBI NIH HHS/ UL1 TR/TR/NCATS NIH HHS/ P30 DK/DK/NIDDK NIH HHS/ U01 DK/DK/NIDDK NIH HHS/ RF1 AG/AG/NIA NIH HHS/ R01 DK/DK/NIDDK NIH HHS/ UH3 DK/DK/NIDDK NIH HHS/ HHSNI/HL/NHLBI NIH HHS/ R01 HL/HL/NHLBI NIH HHS/ U01 DK/DK/NIDDK NIH HHS/ N01HC/HL/NHLBI NIH HHS/ 75ND/HL/NHLBI NIH HHS/ Comparative Study Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Transl Res. Dec;238:49-62. doi: 10./j.trsl..07.005. Epub Jul 31.I SomaScan 08/04/ Jimenez-Balado J, et al. New candidate blood biomarkers potentially associated with white matter hyperintensities progression Sci Rep 11 1 https://www.doi.org/10./s-021--w 34,253,757 Aged Biomarkers/*metabolism Blood-Brain Barrier/metabolism Humans Hypertension/*metabolism Magnetic Resonance Imaging Matrix Metalloproteinase 9/metabolism Middle Aged Neutral Ceramidase/genetics/metabolism Proto-Oncogene Proteins c-met/metabolism White Matter/*metabolism We aimed to discover blood biomarkers associated with longitudinal changes in white matter hyperintensities (WMH). This study was divided into a discovery phase and a replication phase. Subjects in both studies were patients with hypertension, aged 50-70, who underwent two magnetic resonance imaging (MRI) sessions and blood extractions over a 4-year follow-up period. In the discovery phase, we screened proteins in 12 subjects with WMH progression and in 12 matched control subjects. We found that 41 proteins were differentially expressed: 13 were upregulated and 28 were downregulated. We subsequently selected three biomarkers for replication in baseline and follow-up samples in 80 subjects with WMH progression and in 80 control subjects. The selected protein candidates for the replication were MMP9 (matrix metalloproteinase-9), which was higher in cases, MET (hepatocyte growth factor receptor) and ASAH2 (neutral ceramidase), which were both lower in cases of WMH progression. Baseline biomarker concentrations did not predict WMH progression. In contrast, patients with WMH progression presented a steeper decline in MET over time. Furthermore, cases showed higher MMP9 and lower ASAH2 levels than controls at the follow-up. These results indicate that MMP9, MET, and ASAH2 are potentially associated with the progression of WMH, and could therefore be interesting candidates to validate in future studies. Jimenez-Balado, Joan Pizarro, Jesus Riba-Llena, Iolanda Penalba, Anna Faura, Julia Pala, Elena Montaner, Joan Hernandez-Guillamon, Mar Delgado, Pilar eng Research Support, Non-U.S. Gov't England Sci Rep. Jul 12;11(1):. doi: 10./s-021--w.I SomaScan 07/14/ Moin ASM, et al. Soluble Neuropilin-1 Response to Hypoglycemia in Type 2 Diabetes: Increased Risk or Protection in SARS-CoV-2 Infection? Front Endocrinol (Lausanne) 12 https://www.doi.org/10./fendo.. 34,248,841 ADAM Proteins/*metabolism Aged Angiotensin-Converting Enzyme 2/*metabolism Angiotensins/metabolism Covid-19 Diabetes Mellitus, Type 2/*metabolism Female Glucose Clamp Technique Humans Hypoglycemia/*metabolism Male Membrane Proteins/*metabolism Middle Aged Neuropilin-1/*metabolism Protective Factors Renin/metabolism Risk Factors SARS-CoV-2 Semaphorin-3A/*metabolism Vascular Endothelial Growth Factor A/*metabolism ACE inhibitors Adam9 Neuropilin-1 type 2 diabetes commercial or financial relationships that could be construed as a potential conflict of interest. INTRODUCTION: Neuropilin-1(NRP1) is a cofactor that enhances SARS-CoV-2 coronavirus cell infectivity when co-expressed with angiotensin-converting enzyme 2(ACE2). The Renin-Angiotensin System (RAS) is activated in type 2 diabetes (T2D); therefore, the aim of this study was to determine if hypoglycaemia-induced stress in T2D would potentiate serum NRP1(sNRP1) levels, reflecting an increased risk for SARS-CoV-2 infection. METHODS: A case-control study of aged-matched T2D (n = 23) and control (n = 23) subjects who underwent a hyperinsulinemic clamp over 1-hour to hypoglycemia(9 M genetic variants imputed to the HRC panel of ~65,000 haplotypes. The genetic variants with the most significant associations were correlated to proteins that were profiled in the serum of a subset of 224 study participants using a SOMAscan array. The genetic associations were replicated in a genome-wide association study of 480 centenarians and ~800 controls of Ashkenazi Jewish descent. The proteomic associations were replicated in a proteomic scan of approximately Ashkenazi Jewish participants from a third cohort. The analysis replicated a protein signature associated with APOE genotypes and confirmed strong overexpression of BIRC2 (p 1 million controls. We found significant Mendelian randomization results for three proteins (ACE2, P = 1.6 x 10(-6); IFNAR2, P = 9.8 x 10(-11) and IL-10RB, P = 2.3 x 10(-14)) using cis-expression quantitative trait loci genetic instruments that also had strong evidence for colocalization with COVID-19 hospitalization. To disentangle the shared expression quantitative trait loci signal for IL10RB and IFNAR2, we conducted phenome-wide association scans and pathway enrichment analysis, which suggested that IFNAR2 is more likely to play a role in COVID-19 hospitalization. Our findings prioritize trials of drugs targeting IFNAR2 and ACE2 for early management of COVID-19. Gaziano, Liam Giambartolomei, Claudia Pereira, Alexandre C Gaulton, Anna Posner, Daniel C Swanson, Sonja A Ho, Yuk-Lam Iyengar, Sudha K Kosik, Nicole M Vujkovic, Marijana Gagnon, David R Bento, A Patricia Barrio-Hernandez, Inigo Ronnblom, Lars Hagberg, Niklas Lundtoft, Christian Langenberg, Claudia Pietzner, Maik Valentine, Dennis Gustincich, Stefano Tartaglia, Gian Gaetano Allara, Elias Surendran, Praveen Burgess, Stephen Zhao, Jing Hua Peters, James E Prins, Bram P Angelantonio, Emanuele Di Devineni, Poornima Shi, Yunling Lynch, Kristine E DuVall, Scott L Garcon, Helene Thomann, Lauren O Zhou, Jin J Gorman, Bryan R Huffman, Jennifer E O'Donnell, Christopher J Tsao, Philip S Beckham, Jean C Pyarajan, Saiju Muralidhar, Sumitra Huang, Grant D Ramoni, Rachel Beltrao, Pedro Danesh, John Hung, Adriana M Chang, Kyong-Mi Sun, Yan V Joseph, Jacob Leach, Andrew R Edwards, Todd L Cho, Kelly Gaziano, J Michael Butterworth, Adam S Casas, Juan P eng MR/L/1/MRC_/Medical Research Council/United Kingdom RG/13/13//BHF_/British Heart Foundation/United Kingdom MC_UU_/1/MRC_/Medical Research Council/United Kingdom /EC | EU Framework Programme for Research and Innovation H | H Priority Excellent Science | H Marie Sklodowska-Curie Actions (H Excellent Science - Marie Sklodowska-Curie Actions)/ I01 CX/CX/CSRD VA/ MR/S/2/MRC_/Medical Research Council/United Kingdom MC_UU_/7/MRC_/Medical Research Council/United Kingdom I01 BX/BX/BLRD VA/ /Z/16/Z/WT_/Wellcome Trust/United Kingdom MVP001/Department of Veteran Affairs/ RG/18/13//BHF_/British Heart Foundation/United Kingdom MVP035/Office of Research and Development, VA/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Nat Med. Apr;27(4):668-676. doi: 10./s-021--z. Epub Apr 9.I SomaScan 04/11/ Chen RY, et al. A Microbiota-Directed Food Intervention for Undernourished Children N Engl J Med 384 16 - https://www.doi.org/10./NEJMoa 33,826,814 Anthropometry Bangladesh Blood Proteins/analysis Body Weight *Dietary Supplements Feces/microbiology Female *Food, Formulated *Gastrointestinal Microbiome Growth Humans Infant *Infant Nutritional Physiological Phenomena Male Malnutrition/*diet therapy/microbiology Proteome Weight Gain BACKGROUND: More than 30 million children worldwide have moderate acute malnutrition. Current treatments have limited effectiveness, and much remains unknown about the pathogenesis of this condition. Children with moderate acute malnutrition have perturbed development of their gut microbiota. METHODS: In this study, we provided a microbiota-directed complementary food prototype (MDCF-2) or a ready-to-use supplementary food (RUSF) to 123 slum-dwelling Bangladeshi children with moderate acute malnutrition between the ages of 12 months and 18 months. The supplementation was given twice daily for 3 months, followed by 1 month of monitoring. We obtained weight-for-length, weight-for-age, and length-for-age z scores and mid-upper-arm circumference values at baseline and every 2 weeks during the intervention period and at 4 months. We compared the rate of change of these related phenotypes between baseline and 3 months and between baseline and 4 months. We also measured levels of proteins in plasma and 209 bacterial taxa in fecal samples. RESULTS: A total of 118 children (59 in each study group) completed the intervention. The rates of change in the weight-for-length and weight-for-age z scores are consistent with a benefit of MDCF-2 on growth over the course of the study, including the 1-month follow-up. Receipt of MDCF-2 was linked to the magnitude of change in levels of 70 plasma proteins and of 21 associated bacterial taxa that were positively correlated with the weight-for-length z score (P 0.85), and even higher when using protein ratios (AUC up to 0.95), that include some protein pairs with established biological relevance. Our results illustrate the promise of plasma proteomics for diagnosing and deciphering the molecular basis of ME/CFS. Germain, Arnaud Levine, Susan M Hanson, Maureen R eng U54 NS/NS/NINDS NIH HHS/ R01AI/National Institute of Allergy and Infectious Diseases/ Seed funds/Cornell University/ Switzerland Proteomes. Jan 29;9(1):6. doi: 10./proteomes.I SomaScan 02/13/ Richardson TG, et al. Evaluating the effects of cardiometabolic exposures on circulating proteins which may contribute to severe SARS-CoV-2 EBioMedicine 64 https://www.doi.org/10./j.ebiom.. 33,548,839 Biomarkers/blood Body Mass Index C-Reactive Protein/genetics/metabolism COVID-19/*blood/genetics Cardiovascular Diseases/*blood/genetics Female Genome-Wide Association Study Humans Interleukin-1/blood/genetics Interleukin-6/blood/genetics Male SARS-CoV-2/genetics/*metabolism Severity of Illness Index Cardiometabolic risk factors Circulating proteins Covid19 Mendelian randomization SARS-CoV-2 research, and in adherence to the University of Oxford's Clinical Trial Service Unit & Epidemiological Studies Unit (CSTU) staff policy, did not accept personal honoraria or other payments from pharmaceutical companies. All other authors declare no conflicts of interest. BACKGROUND: Developing insight into the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of critical importance to overcome the global pandemic caused by coronavirus disease (covid-19). In this study, we have applied Mendelian randomization (MR) to systematically evaluate the effect of 10 cardiometabolic risk factors and genetic liability to lifetime smoking on 97 circulating host proteins postulated to either interact or contribute to the maladaptive host response of SARS-CoV-2. METHODS: We applied the inverse variance weighted (IVW) approach and several robust MR methods in a two-sample setting to systemically estimate the genetically predicted effect of each risk factor in turn on levels of each circulating protein. Multivariable MR was conducted to simultaneously evaluate the effects of multiple risk factors on the same protein. We also applied MR using cis-regulatory variants at the genomic location responsible for encoding these proteins to estimate whether their circulating levels may influence severe SARS-CoV-2. FINDINGS: In total, we identified evidence supporting 105 effects between risk factors and circulating proteins which were robust to multiple testing corrections and sensitivity analyzes. For example, body mass index provided evidence of an effect on 23 circulating proteins with a variety of functions, such as inflammatory markers c-reactive protein (IVW Beta=0.34 per standard deviation change, 95% CI=0.26 to 0.41, P = 2.19 x 10(-16)) and interleukin-1 receptor antagonist (IVW Beta=0.23, 95% CI=0.17 to 0.30, P = 9.04 x 10(-12)). Further analyzes using multivariable MR provided evidence that the effect of BMI on lowering immunoglobulin G, an antibody class involved in protection from infection, is substantially mediated by raised triglycerides levels (IVW Beta=-0.18, 95% CI=-0.25 to -0.12, P = 2.32 x 10(-08), proportion mediated=44.1%). The strongest evidence that any of the circulating proteins highlighted by our initial analysis influence severe SARS-CoV-2 was identified for soluble glycoprotein 130 (odds ratio=1.81, 95% CI=1.25 to 2.62, P = 0.002), a signal transductor for interleukin-6 type cytokines which are involved in inflammatory response. However, based on current case samples for severe SARS-CoV-2 we were unable to replicate findings in independent samples. INTERPRETATION: Our findings highlight several key proteins which are influenced by established exposures for disease. Future research to determine whether these circulating proteins mediate environmental effects onto risk of SARS-CoV-2 infection or covid-19 progression are warranted to help elucidate therapeutic strategies for severe covid-19 disease. FUNDING: The Medical Research Council, the Wellcome Trust, the British Heart Foundation and UK Research and Innovation. Richardson, Tom G Fang, Si Mitchell, Ruth E Holmes, Michael V Davey Smith, George eng MC_UU_/1/MRC_/Medical Research Council/United Kingdom MR/S/1/MRC_/Medical Research Council/United Kingdom Evaluation Study Netherlands EBioMedicine. Feb;64:. doi: 10./j.ebiom... Epub Feb 3.I SomaScan 02/07/ Matsuda K, et al. A replication-competent adenovirus-vectored influenza vaccine induces durable systemic and mucosal immunity J Clin Invest 131 5 https://www.doi.org/10./JCI 33,529,172 Adenoviruses, Human/*genetics/immunology/physiology Administration, Oral Adolescent Adult Antibodies, Neutralizing/blood Antibodies, Viral/blood Antigens, Viral/genetics Female *Genetic Vectors Hemagglutinin Glycoproteins, Influenza Virus/genetics/immunology Humans Immunity, Cellular Immunity, Humoral Immunity, Mucosal Influenza A Virus, H5N1 Subtype/genetics/immunology Influenza Vaccines/*administration & dosage/genetics/*immunology Influenza, Human/immunology/prevention & control Male Nasal Sprays Palatine Tonsil Virus Replication Virus Shedding Young Adult Adaptive immunity Beta cells Immunology Influenza Vaccines adenovirus type 4 SAR-CoV-2 vaccines and their use BACKGROUNDTo understand the features of a replicating vaccine that might drive potent and durable immune responses to transgene-encoded antigens, we tested a replication-competent adenovirus type 4 encoding influenza virus H5 HA (Ad4-H5-Vtn) administered as an oral capsule or via tonsillar swab or nasal spray.METHODSViral shedding from the nose, mouth, and rectum was measured by PCR and culturing. H5-specific IgG and IgA antibodies were measured by bead array binding assays. Serum antibodies were measured by a pseudovirus entry inhibition, microneutralization, and HA inhibition assays.RESULTSAd4-H5-Vtn DNA was shed from most upper respiratory tract-immunized (URT-immunized) volunteers for 2 to 4 weeks, but cultured from only 60% of participants, with a median duration of 1 day. Ad4-H5-Vtn vaccination induced increases in H5-specific CD4+ and CD8+ T cells in the peripheral blood as well as increases in IgG and IgA in nasal, cervical, and rectal secretions. URT immunizations induced high levels of serum neutralizing antibodies (NAbs) against H5 that remained stable out to week 26. The duration of viral shedding correlated with the magnitude of the NAb response at week 26. Adverse events (AEs) were mild, and peak NAb titers were associated with overall AE frequency and duration. Serum NAb titers could be boosted to very high levels 2 to 5 years after Ad4-H5-Vtn vaccination with recombinant H5 or inactivated split H5N1 vaccine.CONCLUSIONReplicating Ad4 delivered to the URT caused prolonged exposure to antigen, drove durable systemic and mucosal immunity, and proved to be a promising platform for the induction of immunity against viral surface glycoprotein targets.TRIAL REGISTRATIONClinicalTrials.gov NCT and NCT.FUNDINGIntramural and Extramural Research Programs of the NIAID, NIH (U19 AI) and the Centers of Excellence for Influenza Research and Surveillance (CEIRS), NIAID, NIH (contract HHSNC). Matsuda, Kenta Migueles, Stephen A Huang, Jinghe Bolkhovitinov, Lyuba Stuccio, Sarah Griesman, Trevor Pullano, Alyssa A Kang, Byong H Ishida, Elise Zimmerman, Matthew Kashyap, Neena Martins, Kelly M Stadlbauer, Daniel Pederson, Jessica Patamawenu, Andy Wright, Nathaniel Shofner, Tulley Evans, Sean Liang, C Jason Candia, Julian Biancotto, Angelique Fantoni, Giovanna Poole, April Smith, Jon Alexander, Jeff Gurwith, Marc Krammer, Florian Connors, Mark eng HHSNC/AI/NIAID NIH HHS/ U19 AI/AI/NIAID NIH HHS/ Clinical Trial, Phase I Randomized Controlled Trial Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't J Clin Invest. Mar 1;131(5):e. doi: 10./JCI.I SomaScan 02/03/ Sebastiani P, et al. Protein signatures of centenarians and their offspring suggest centenarians age slower than other humans Aging Cell 20 2 e https://www.doi.org/10./acel. 33,512,769 Aged Aged, 80 and over *Aging Blood Proteins/*metabolism Cellular Senescence Humans SomaLogic aging longevity protein senescence and stockholder of Regeneron Pharmaceuticals. Using samples from the New England Centenarian Study (NECS), we sought to characterize the serum proteome of 77 centenarians, 82 centenarians' offspring, and 65 age-matched controls of the offspring (mean ages: 105, 80, and 79 years). We identified proteins that significantly differ between centenarians and their offspring and controls (FDR /= 55 years (STD beta = - 0.12, p = 0.). ACEi treatment was also independently associated with significantly lower ACE2 levels, and ACE2 was inversely associated with weight, and positively associated with peripheral artery disease (PAD) status. There was a trend toward higher circulating ACE2 levels in hypertensive individuals, but it did not reach statistical significance. In a stratified analysis, the association between log (ACE2) and log (IL-6) was more evidenced in participants with PAD. Circulating ACE2 levels demonstrate curvilinear association with age, with older individuals beyond the sixth decade age having lower levels. ACEi was associated with greater circulating ACE2 levels. Interestingly, ACE2 was elevated in PAD and positively associated with inflammatory markers, suggesting compensatory upregulation in the setting of chronic inflammation. Further studies are needed to comprehensively characterize RAAS components with aging and disease, and assess its prognostic role in predicting COVID-19 outcomes. AlGhatrif, Majd Tanaka, Toshiko Moore, Ann Zenobia Bandinelli, Stefania Lakatta, Edward G Ferrucci, Luigi eng Research Support, N.I.H., Intramural Switzerland Geroscience. Apr;43(2):619-627. doi: 10./s-020--w. Epub Jan 18.I SomaScan 01/20/ Sharma R, et al. Circulating markers of NADH-reductive stress correlate with mitochondrial disease severity J Clin Invest 131 2 https://www.doi.org/10./JCI 33,463,549 Adolescent Adult Aged Aged, 80 and over Alanine/blood Biomarkers/blood Child Child, Preschool Female Growth Differentiation Factor 15/blood Humans Hydroxybutyrates/blood Lactic Acid/blood MELAS Syndrome/*blood/genetics Male Middle Aged Mutation Severity of Illness Index Genetics Intermediary metabolism Metabolism Mitochondria Monogenic diseases Ret Hs6st1 sE-selectin integrated stress response creatine pyruvate 2-hydroxybutyrate alpha-hydroxybutyrate lactoyl-amino acids hydroxy-fatty acids hydroxy-acylcarnitines Mitochondrial disorders represent a large collection of rare syndromes that are difficult to manage both because we do not fully understand biochemical pathogenesis and because we currently lack facile markers of severity. The m.A>G variant is the most common heteroplasmic mitochondrial DNA mutation and underlies a spectrum of diseases, notably mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes (MELAS). To identify robust circulating markers of m.A>G disease, we first performed discovery proteomics, targeted metabolomics, and untargeted metabolomics on plasma from a deeply phenotyped cohort (102 patients, 32 controls). In a validation phase, we measured concentrations of prioritized metabolites in an independent cohort using distinct methods. We validated 20 analytes (1 protein, 19 metabolites) that distinguish patients with MELAS from controls. The collection includes classic (lactate, alanine) and more recently identified (GDF-15, alpha-hydroxybutyrate) mitochondrial markers. By mining untargeted mass-spectra we uncovered 3 less well-studied metabolite families: N-lactoyl-amino acids, beta-hydroxy acylcarnitines, and beta-hydroxy fatty acids. Many of these 20 analytes correlate strongly with established measures of severity, including Karnofsky status, and mechanistically, nearly all markers are attributable to an elevated NADH/NAD+ ratio, or NADH-reductive stress. Our work defines a panel of organelle function tests related to NADH-reductive stress that should enable classification and monitoring of mitochondrial disease. Sharma, Rohit Reinstadler, Bryn Engelstad, Kristin Skinner, Owen S Stackowitz, Erin Haller, Ronald G Clish, Clary B Pierce, Kerry Walker, Melissa A Fryer, Robert Oglesbee, Devin Mao, Xiangling Shungu, Dikoma C Khatri, Ashok Hirano, Michio De Vivo, Darryl C Mootha, Vamsi K eng F32 GM/GM/NIGMS NIH HHS/ P01 HD/HD/NICHD NIH HHS/ P30 DK/DK/NIDDK NIH HHS/ R01 AR/AR/NIAMS NIH HHS/ Clinical Trial Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't J Clin Invest. Jan 19;131(2):e. doi: 10./JCI.I SomaScan 01/20/ Ngo LH, et al. Plasma protein expression profiles, cardiovascular disease, and religious struggles among South Asians in the MASALA study Sci Rep 11 1 961 https://www.doi.org/10./s-020--1 33,441,605 Aged Asian Americans/*psychology Biomarkers/blood/metabolism Blood Proteins/*metabolism Cardiovascular Diseases/*blood/*metabolism Case-Control Studies Cell Differentiation/physiology Female Humans Incidence Logistic Models Male Middle Aged Proteomics/methods Religion Risk Factors United States Blood protein concentrations are clinically useful, predictive biomarkers of cardiovascular disease (CVD). Despite a higher burden of CVD among U.S. South Asians, no CVD-related proteomics study has been conducted in this sub-population. The aim of this study is to investigate the associations between plasma protein levels and CVD incidence, and to assess the potential influence of religiosity/spirituality (R/S) on significant protein-CVD associations, in South Asians from the MASALA Study. We used a nested case-control design of 50 participants with incident CVD and 50 sex- and age-matched controls. Plasma samples were analyzed by SOMAscan for expression of proteins. Multivariable logistic regression models and model selection using Akaike Information Criteria were performed on the proteins and clinical covariates, with further effect modification analyses conducted to assess the influence of R/S measures on significant associations between proteins and incident CVD events. We identified 36 proteins that were significantly expressed differentially among CVD cases compared to matched controls. These proteins are involved in immune cell recruitment, atherosclerosis, endothelial cell differentiation, and vascularization. A final multivariable model found three proteins (Contactin-5 [CNTN5], Low affinity immunoglobulin gamma Fc region receptor II-a [FCGR2A], and Complement factor B [CFB]) associated with incident CVD after adjustment for diabetes (AUC = 0.82). Religious struggles that exacerbate the adverse impact of stressful life events, significantly modified the effect of Contactin-5 and Complement factor B on risk of CVD. Our research is this first assessment of the relationship between protein concentrations and risk of CVD in a South Asian sample. Further research is needed to understand patterns of proteomic profiles across diverse ethnic communities, and the influence of resources for resiliency on proteomic signatures and ultimately, risk of CVD. Ngo, Long H Austin Argentieri, M Dillon, Simon T Kent, Blake Victor Kanaya, Alka M Shields, Alexandra E Libermann, Towia A eng R01 HL/HL/NHLBI NIH HHS/ K24 HL/HL/NHLBI NIH HHS/ UL1 RR/NH/NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England Sci Rep. Jan 13;11(1):961. doi: 10./s-020--1.I SomaScan 01/15/ Xu X, et al. Inhibition of the Complement Alternative Pathway by Chemically Modified DNA Aptamers That Bind with Picomolar Affinity to Factor B J Immunol 206 4 861-873 https://www.doi.org/10./jimmunol. 33,419,768 *Aptamers, Nucleotide/chemistry/immunology Complement C3/chemistry/immunology *Complement Factor B/chemistry/immunology *Complement Pathway, Alternative Humans The complement system is a conserved component of innate immunity that fulfills diverse roles in defense and homeostasis. Inappropriate activation of complement contributes to many inflammatory diseases, however, which has led to a renewed emphasis on development of therapeutic complement inhibitors. Activation of complement component C3 is required for amplification of complement and is achieved through two multisubunit proteases called C3 convertases. Of these, the alternative pathway (AP) C3 convertase is responsible for a majority of the C3 activation products in vivo, which renders it an attractive target for inhibitor discovery. In this study, we report the identification and characterization of two related slow off-rate modified DNA aptamers (SOMAmer) reagents that inhibit formation of the AP C3 convertase by binding to the proprotease, factor B (FB). These aptamers, known as SL (31 bases) and SL (29 bases), contain uniform substitutions of 5-(N-2-naphthylethylcarboxyamide)-2'-deoxyuridine for deoxythymidine. SL and SL bind FB with K (d) values of 49 and 88 pM, respectively, and inhibit activation of C3 and lysis of rabbit erythrocytes under AP-specific conditions. Cocrystal structures of SL (3.4 A) and SL (3.1 A) bound to human FB revealed that SL and SL recognize a site at the juncture of the CCP1, CCP3, and vWF domains of FB. Consistent with these structures and previously published information, these aptamers inhibited FB binding to C3b and blocked formation of the AP C3 convertase. Together, these results demonstrate potent AP inhibition by modified DNA aptamers and expand the pipeline of FB-binding molecules with favorable pharmacologic properties. Xu, Xin Zhang, Chi Denton, Dalton T O'Connell, Daniel Drolet, Daniel W Geisbrecht, Brian V eng R21 AI/AI/NIAID NIH HHS/ R21 NS/NS/NINDS NIH HHS/ Research Support, N.I.H., Extramural J Immunol. Feb 15;206(4):861-873. doi: 10./jimmunol.. Epub Jan 8.I SomaScan 01/10/ Abdel-Aziz MI, et al. Association of endopeptidases, involved in SARS-CoV-2 infection, with microbial aggravation in sputum of severe asthma Allergy 76 6 - https://www.doi.org/10./all. 33,411,967 *Asthma/diagnosis *covid-19 Endopeptidases Humans SARS-CoV-2 Sputum Abdel-Aziz, Mahmoud I Kermani, Nazanin Zounemat Neerincx, Anne H Vijverberg, Susanne J H Guo, Yike Howarth, Peter Dahlen, Sven-Erik Djukanovic, Ratko Sterk, Peter J Kraneveld, Aletta D Maitland-van der Zee, Anke H Chung, Kian Fan Adcock, Ian M eng /Innovative Medicines Initiative/ European Federation of Pharmaceutical Industries and Associations/ FP7/-/Seventh Framework Programme/ Letter Research Support, Non-U.S. Gov't Denmark Allergy. Jun;76(6):-. doi: 10./all.. Epub Jan 25.I SomaScan 01/08/ Ozen A, et al. Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease Nat Immunol 22 2 128-139 https://www.doi.org/10./s-020--z 33,398,182 Antibodies, Monoclonal, Humanized/adverse effects/pharmacokinetics/*therapeutic use Biomarkers/blood CD55 Antigens/deficiency/genetics Complement Activation/*drug effects Complement C5/*antagonists & inhibitors/metabolism Complement Inactivating Agents/adverse effects/pharmacokinetics/*therapeutic use Energy Metabolism/*drug effects Genetic Predisposition to Disease Humans Hypoproteinemia/*drug therapy/genetics/immunology/metabolism Immunity, Innate/*drug effects Mutation Phenotype Protein-Losing Enteropathies/*drug therapy/genetics/immunology/metabolism Treatment Outcome Complement hyperactivation, angiopathic thrombosis and protein-losing enteropathy (CHAPLE disease) is a lethal disease caused by genetic loss of the complement regulatory protein CD55, leading to overactivation of complement and innate immunity together with immunodeficiency due to immunoglobulin wasting in the intestine. We report in vivo human data accumulated using the complement C5 inhibitor eculizumab for the medical treatment of patients with CHAPLE disease. We observed cessation of gastrointestinal pathology together with restoration of normal immunity and metabolism. We found that patients rapidly renormalized immunoglobulin concentrations and other serum proteins as revealed by aptamer profiling, re-established a healthy gut microbiome, discontinued immunoglobulin replacement and other treatments and exhibited catch-up growth. Thus, we show that blockade of C5 by eculizumab effectively re-establishes regulation of the innate immune complement system to substantially reduce the pathophysiological manifestations of CD55 deficiency in humans. Ozen, Ahmet Kasap, Nurhan Vujkovic-Cvijin, Ivan Apps, Richard Cheung, Foo Karakoc-Aydiner, Elif Akkelle, Bilge Sari, Sinan Tutar, Engin Ozcay, Figen Uygun, Dilara Kocacik Islek, Ali Akgun, Gamze Selcuk, Merve Sezer, Oya Balci Zhang, Yu Kutluk, Gunsel Topal, Erdem Sayar, Ersin Celikel, Cigdem Houwen, Roderick H J Bingol, Aysen Ogulur, Ismail Eltan, Sevgi Bilgic Snow, Andrew L Lake, Camille Fantoni, Giovanna Alba, Camille Sellers, Brian Chauvin, Samuel D Dalgard, Clifton L Harari, Olivier Ni, Yan G Wang, Ming-Dauh Devalaraja-Narashimha, Kishor Subramanian, Poorani Ergelen, Rabia Artan, Reha Guner, Sukru Nail Dalgic, Buket Tsang, John Belkaid, Yasmine Ertem, Deniz Baris, Safa Lenardo, Michael J eng R01 GM/GM/NIGMS NIH HHS/ Z01 AI/ImNIH/Intramural NIH HHS/ Observational Study Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Nat Immunol. Feb;22(2):128-139. doi: 10./s-020--z. Epub Jan 4.I SomaScan 01/06/ Corlin L, et al. Proteomic Signatures of Lifestyle Risk Factors for Cardiovascular Disease: A Cross-Sectional Analysis of the Plasma Proteome in the Framingham Heart Study J Am Heart Assoc 10 1 e https://www.doi.org/10./JAHA.120. 33,372,532 *Alcohol Drinking/epidemiology/metabolism *Cardiovascular Diseases/blood/epidemiology/genetics Effect Modifier, Epidemiologic Exercise/*physiology Female Genome-Wide Association Study *Heart Disease Risk Factors Humans *Life Style Longitudinal Studies Male Middle Aged Mortality Proteomics/*methods Quantitative Trait Loci *Smoking/epidemiology/metabolism United States/epidemiology alcohol consumption lifestyle physical activity proteomics smoking Background Proteomic biomarkers related to cardiovascular disease risk factors may offer insights into the pathogenesis of cardiovascular disease. We investigated whether modifiable lifestyle risk factors for cardiovascular disease are associated with distinctive proteomic signatures. Methods and Results We analyzed circulating plasma proteomic biomarkers (assayed using the SomaLogic platform) in 897 FHS (Framingham Heart Study) Generation 3 participants (mean age 46+/-8 years; 56% women; discovery sample) and FOS (Framingham Offspring Study) participants (mean age 52 years; 54% women; validation sample). Participants were free of hypertension, diabetes mellitus, and clinical cardiovascular disease. We used linear mixed effects models (adjusting for age, sex, body mass index, and family structure) to relate levels of each inverse-log transformed protein to 3 lifestyle factors (ie, smoking, alcohol consumption, and physical activity). A Bonferroni-adjusted P value indicated statistical significance (based on number of proteins and traits tested, P/=1.5 between postoperative day 2 (POD2) and preoperative (PREOP) identified functional pathways with major effects on pro-inflammatory proteins. Chitinase-3-like protein 1 (CHI3L1), C-reactive protein (CRP), and interleukin-6 (IL-6) were independently validated in separate validation cohorts from SAGES (n = 150 for CRP, IL-6; n = 126 for CHI3L1). Foldchange CHI3L1 and IL-6 were associated with increased postoperative complications [relative risk (RR) 1.50, 95% confidence interval (95% CI) 1.21-1.85 and RR 1.63, 95% CI 1.18-2.26, respectively], length of stay (RR 1.35, 95% CI 0.77-1.92 and RR 0.98, 95% CI 0.52-1.45), and risk of discharge to postacute facility (RR 1.15, 95% CI 1.04-1.26 and RR 1.11, 95% CI 1.04-1.18); POD2 and PREOP CRP difference was associated with discharge to postacute facility (RR 1.14, 95% CI 1.04-1.25). CONCLUSION: SOMAscan can identify novel and clinically relevant surgery-induced protein changes. Ultimately, proteomics may provide insights about pathways by which surgical stress contributes to postoperative outcomes. Fong, Tamara G Chan, Noel Y Dillon, Simon T Zhou, Wenxiao Tripp, Bridget Ngo, Long H Otu, Hasan H Inouye, Sharon K Vasunilashorn, Sarinnapha M Cooper, Zara Xie, Zhongcong Marcantonio, Edward R Libermann, Towia A eng R01 AG/AG/NIA NIH HHS/ R03 AG/AG/NIA NIH HHS/ K24 AG/AG/NIA NIH HHS/ K07 AG/AG/NIA NIH HHS/ K01 AG/AG/NIA NIH HHS/ T32 AT/AT/NCCIH NIH HHS/ P01 AG/AG/NIA NIH HHS/ UL1 TR/TR/NCATS NIH HHS/ R21 AG/AG/NIA NIH HHS/ R24 AG/AG/NIA NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Ann Surg. Apr 1;273(4):732-742. doi: 10./SLA..I SomaScan 04/05/ Arthur L, et al. Cellular and plasma proteomic determinants of COVID-19 and non-COVID-19 pulmonary diseases relative to healthy aging Nature Aging 1 6 535-549 https://www.doi.org/10./s-021--x We examine the cellular and soluble determinants of coronavirus disease (COVID-19) relative to aging by performing mass cytometry in parallel with clinical blood testing and plasma proteomic profiling of ~4,700 proteins from 71 individuals with pulmonary disease and 148 healthy donors (25–80 years old). Distinct cell populations were associated with age (GZMK+CD8+ T cells and CD25low CD4+ T cells) and with COVID-19 (TBET_EOMES_ CD4+ T cells, HLA-DR+CD38+ CD8+ T cells and CD27+CD38+ B cells). A unique population of TBET+EOMES+ CD4+ T cells was associated with individuals with COVID-19 who experienced moderate, rather than severe or lethal, disease. Disease severity correlated with blood creatinine and urea nitrogen levels. Proteomics revealed a major impact of age on the disease-associated plasma signatures and highlighted the divergent contribution of hepatocyte and muscle secretomes to COVID-19 plasma proteins. Aging plasma was enriched in matrisome proteins and heart/aorta smooth muscle cell-specific proteins. These findings reveal age-specific and disease-specific changes associated with COVID-19, and potential soluble mediators of the physiological impact of COVID-19. Arthur, Laura Esaulova, Ekaterina Mogilenko, Denis A. Tsurinov, Petr Burdess, Samantha Laha, Anwesha Presti, Rachel Goetz, Brian Watson, Mark A. Goss, Charles W. Gurnett, Christina A. Mudd, Philip A. Beers, Courtney O’Halloran, Jane A. Artyomov, Maxim N. SomaScan Moin ASM, et al. Hypoglycemia-induced changes in complement pathways in type 2 diabetes Atherosclerosis Plus 46 35-45 https://www.doi.org/10./j.athplu..11.002 Hypoglycemia Type 2 diabetes Complement proteins Proteomics An association between hypoglycaemia and adverse cardiovascular events has been suggested from longitudinal and retrospective cohort studies. The complement pathway proteins in hypoglycemia are not well studied. Here, we hypothesized that these circulating proteins would be elevated in response to hypoglycemia in type 2 diabetes (T2D) through the inflammatory response. Moin, Abu Saleh Md Nandakumar, Manjula Diboun, Ilhame Al-Qaissi, Ahmed Sathyapalan, Thozhukat Atkin, Stephen L. Butler, Alexandra E. SomaScan Walker KA, et al. Large-scale plasma proteomic analysis identifies proteins and pathways associated with dementia risk Nature Aging 1 5 473-489 https://www.doi.org/10./s-021--0 The plasma proteomic changes that precede the onset of dementia could yield insights into disease biology and highlight new biomarkers and avenues for intervention. We quantified 4,877 plasma proteins in nondemented older adults in the Atherosclerosis Risk in Communities cohort and performed a proteome-wide association study of dementia risk over five years (n_=_4,110; 428 incident cases). Thirty-eight proteins were associated with incident dementia after Bonferroni correction. Of these, 16 were also associated with late-life dementia risk when measured in plasma collected nearly 20 years earlier, during mid-life. Two-sample Mendelian randomization causally implicated two dementia-associated proteins (SVEP1 and angiostatin) in Alzheimer’s disease. SVEP1, an immunologically relevant cellular adhesion protein, was found to be part of larger dementia-associated protein networks, and circulating levels were associated with atrophy in brain regions vulnerable to Alzheimer’s pathology. Pathway analyses for the broader set of dementia-associated proteins implicated immune, lipid, metabolic signaling and hemostasis pathways in dementia pathogenesis. Walker, Keenan A. Chen, Jingsha Zhang, Jingning Fornage, Myriam Yang, Yunju Zhou, Linda Grams, Morgan E. Tin, Adrienne Daya, Natalie Hoogeveen, Ron C. Wu, Aozhou Sullivan, Kevin J. Ganz, Peter Zeger, Scott L. Gudmundsson, Elias F. Emilsson, Valur Launer, Lenore J. Jennings, Lori L. Gudnason, Vilmundur Chatterjee, Nilanjan Gottesman, Rebecca F. Mosley, Thomas H. Boerwinkle, Eric Ballantyne, Christie M. Coresh, Josef SomaScan Morani F, et al. Functional Network Profiles in ARSACS Disclosed by Aptamer-Based Proteomic Technology Front Neurol 11 https://www.doi.org/10./fneur.. 33,584,503 Arsacs SomaLogic technology engulfment of cells neuroinflammation proteomic analysis sacsin synaptogenesis commercial or financial relationships that could be construed as a potential conflict of interest. Although the genetic basis of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) has been uncovered, our poor understanding of disease mechanisms requires new light on functional pathways and modifying factors to improve early diagnostic strategies and offer alternative treatment options in a rare condition with no cure. Investigation of the pathologic state combining disease models and quantitative omic approach might improve biomarkers discovery with possible implications in patients' diagnoses. In this study, we analyzed proteomics data obtained using the SomaLogic technology, comparing cell lysates from ARSACS patients and from a SACS KO SH-SY5Y neuroblastoma cell model. Single-stranded deoxyoligonucleotides, selected in vitro from large random libraries, bound and quantified molecular targets related to the neuroinflammation signaling pathway and to neuronal development. Changes in protein levels were further analyzed by bioinformatics and network approaches to identify biomarkers of ARSACS and functional pathways impaired in the disease. We identified novel significantly dysregulated biological processes related to neuroinflammation, synaptogenesis, and engulfment of cells in patients and in KO cells compared with controls. Among the differential expressed proteins found in this work, we identified several proteins encoded by genes already known to be mutated in other forms of neurodegeneration. This finding suggests that common dysfunctional networks could be therapeutic targets for future investigations. Morani, Federica Doccini, Stefano Chiorino, Giovanna Fattori, Fabiana Galatolo, Daniele Sciarrillo, Elisa Gemignani, Federica Zuchner, Stephan Bertini, Enrico Silvio Santorelli, Filippo Maria eng Switzerland Front Neurol. Jan 27;11:. doi: 10./fneur... eCollection .I SomaScan 02/16/ Oyama Y, et al. Intense light as anticoagulant therapy in humans PLoS One 15 12 e https://www.doi.org/10./journal.pone. 33,382,840 Animals Blood Coagulation/*physiology Blood Platelets/*metabolism Humans Light Male Mice Myocardial Ischemia/blood/*metabolism Myocardial Reperfusion Injury/blood/*metabolism Period Circadian Proteins/genetics/*metabolism *Phototherapy Platelet Aggregation/physiology Proteomics Blood coagulation is central to myocardial ischemia and reperfusion (IR) injury. Studies on the light elicited circadian rhythm protein Period 2 (PER2) using whole body Per2-/- mice found deficient platelet function and reduced clotting which would be expected to protect from myocardial IR-injury. In contrast, intense light induction of PER2 protected from myocardial IR-injury while Per2 deficiency was detrimental. Based on these conflicting data, we sought to evaluate the role of platelet specific PER2 in coagulation and myocardial ischemia and reperfusion injury. We demonstrated that platelets from mice with tissue-specific deletion of Per2 in the megakaryocyte lineage (Per2loxP/loxP-PF4-CRE) significantly clot faster than platelets from control mice. We further found increases in infarct sizes or plasma troponin levels in Per2loxP/loxP-PF4-CRE mice when compared to controls. As intense light increases PER2 protein in human tissues, we also performed translational studies and tested the effects of intense light therapy on coagulation in healthy human subjects. Our human studies revealed that intense light therapy repressed procoagulant pathways in human plasma samples and significantly reduced the clot rate. Based on these results we conclude that intense light elicited PER2 has an inhibitory function on platelet aggregation in mice. Further, we suggest intense light as a novel therapy to prevent or treat clotting in a clinical setting. Oyama, Yoshimasa Shuff, Sydney Davizon-Castillo, Pavel Clendenen, Nathan Eckle, Tobias eng R01 HL/HL/NHLBI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't PLoS One. Dec 31;15(12):e. doi: 10./journal.pone.. eCollection .I SomaScan 01/01/ Narasimhan A, et al. Identification of Potential Serum Protein Biomarkers and Pathways for Pancreatic Cancer Cachexia Using an Aptamer-Based Discovery Platform Cancers (Basel) 12 12 https://www.doi.org/10./cancers 33,334,063 biomarkers cachexia humans neoplasms pancreatic adenocarcinoma paracrine communication proteome weight loss Patients with pancreatic ductal adenocarcinoma (PDAC) suffer debilitating and deadly weight loss, known as cachexia. Development of therapies requires biomarkers to diagnose, and monitor cachexia; however, no such markers are in use. Via Somascan, we measured ~ plasma proteins in 30 patients with PDAC vs. 11 controls. We found 60 proteins specific to local PDAC, 46 to metastatic, and 67 to presence of >5% cancer weight loss (FC >/= |1.5|, p = 0.05). Six were common for cancer stage (Up: GDF15, TIMP1, IL1RL1; Down: CCL22, APP, CLEC1B). Four were common for local/cachexia (C1R, PRKCG, ELANE, SOST: all oppositely regulated) and four for metastatic/cachexia (SERPINA6, PDGFRA, PRSS2, PRSS1: all consistently changed), suggesting that stage and cachexia status might be molecularly separable. We found 71 proteins that correlated with cachexia severity via weight loss grade, weight loss, skeletal muscle index and radiodensity (r >/= |0.50|, p = 0.05), including some known cachexia mediators/markers (LEP, MSTN, ALB) as well as novel proteins (e.g., LYVE1, C7, F2). Pathway, correlation, and upstream regulator analyses identified known (e.g., IL6, proteosome, mitochondrial dysfunction) and novel (e.g., Wnt signaling, NK cells) mechanisms. Overall, this study affords a basis for validation and provides insights into the processes underpinning cancer cachexia. Narasimhan, Ashok Shahda, Safi Kays, Joshua K Perkins, Susan M Cheng, Lijun Schloss, Katheryn N H Schloss, Daniel E I Koniaris, Leonidas G Zimmers, Teresa A eng No number/Heroes Foundation/ R01-CA/CA/NCI NIH HHS/ No number/Lustgarten Foundation/ No number/Lilly Endowment/ R01-CA/CA/NCI NIH HHS/ No number/IUPUI Signature Center for Pancreatic Cancer Research/ I01 BX/BX/BLRD VA/ R01-DK/DK/NIDDK NIH HHS/ P30-CA/CA/NCI NIH HHS/ I01 CX/CX/CSRD VA/ Switzerland Cancers (Basel). Dec 15;12(12):. doi: 10./cancers.I SomaScan 12/19/ Zampino M, et al. A Plasma Proteomic Signature of Skeletal Muscle Mitochondrial Function Int J Mol Sci 21 24 https://www.doi.org/10./ijms 33,333,910 Adult Aged Aged, 80 and over Energy Metabolism/physiology Female Gene Ontology Humans Inflammation/blood Magnetic Resonance Spectroscopy Male Middle Aged Mitochondria/*metabolism Muscle, Skeletal/*metabolism Oxidative Stress/physiology Plasma/*metabolism Proteome/*metabolism Proteomics Reactive Oxygen Species/metabolism SOMAscan aptamers inflammation mitochondria oxidative capacity phosphorous magnetic resonance spectroscopy plasma skeletal muscle Although mitochondrial dysfunction has been implicated in aging, physical function decline, and several age-related diseases, an accessible and affordable measure of mitochondrial health is still lacking. In this study we identified the proteomic signature of muscular mitochondrial oxidative capacity in plasma. In 165 adults, we analyzed the association between concentrations of plasma proteins, measured using the SOMAscan assay, and skeletal muscle maximal oxidative phosphorylation capacity assessed as post-exercise phosphocreatine recovery time constant (tau(PCr)) by phosphorous magnetic resonance spectroscopy. Out of proteins analyzed, we identified 87 proteins significantly associated with tau(PCr), adjusting for age, sex, and phosphocreatine depletion. Sixty proteins were positively correlated with better oxidative capacity, while 27 proteins were correlated with poorer capacity. Specific clusters of plasma proteins were enriched in the following pathways: homeostasis of energy metabolism, proteostasis, response to oxidative stress, and inflammation. The generalizability of these findings would benefit from replication in an independent cohort and in longitudinal analyses. Zampino, Marta Tanaka, Toshiko Ubaida-Mohien, Ceereena Fantoni, Giovanna Candia, Julian Semba, Richard D Ferrucci, Luigi eng R01 AG/AG/NIA NIH HHS/ R01 AG/NH/NIH HHS/ Switzerland Int J Mol Sci. Dec 15;21(24):. doi: 10./ijms.I SomaScan 12/19/ Pietzner M, et al. Genetic architecture of host proteins involved in SARS-CoV-2 infection Nat Commun 11 1 https://www.doi.org/10./s-020--z 33,328,453 ABO Blood-Group System/metabolism Aptamers, Peptide/blood/metabolism Blood Coagulation COVID-19/*genetics/*virology Drug Delivery Systems Female Gene Expression Regulation Host-Derived Cellular Factors/metabolism Host-Pathogen Interactions/*genetics Humans Internet Male Middle Aged Proteins/*genetics Quantitative Trait Loci/genetics SARS-CoV-2/*physiology Understanding the genetic architecture of host proteins interacting with SARS-CoV-2 or mediating the maladaptive host response to COVID-19 can help to identify new or repurpose existing drugs targeting those proteins. We present a genetic discovery study of 179 such host proteins among 10,708 individuals using an aptamer-based technique. We identify 220 host DNA sequence variants acting in cis (MAF 0.01-49.9%) and explaining 0.3-70.9% of the variance of 97 of these proteins, including 45 with no previously known protein quantitative trait loci (pQTL) and 38 encoding current drug targets. Systematic characterization of pQTLs across the phenome identified protein-drug-disease links and evidence that putative viral interaction partners such as MARK3 affect immune response. Our results accelerate the evaluation and prioritization of new drug development programmes and repurposing of trials to prevent, treat or reduce adverse outcomes. Rapid sharing and detailed interrogation of results is facilitated through an interactive webserver ( https://omicscience.org/apps/covidpgwas/ ). Pietzner, Maik Wheeler, Eleanor Carrasco-Zanini, Julia Raffler, Johannes Kerrison, Nicola D Oerton, Erin Auyeung, Victoria P W Luan, Jian'an Finan, Chris Casas, Juan P Ostroff, Rachel Williams, Steve A Kastenmuller, Gabi Ralser, Markus Gamazon, Eric R Wareham, Nicholas J Hingorani, Aroon D Langenberg, Claudia eng MC_UU_/1/MRC_/Medical Research Council/United Kingdom R01 HG/HG/NHGRI NIH HHS/ FC/MRC_/Medical Research Council/United Kingdom DH_/Department of Health/United Kingdom U19 AG/AG/NIA NIH HHS/ MC_PC_/MRC_/Medical Research Council/United Kingdom AA/18/6//BHF_/British Heart Foundation/United Kingdom RF1 AG/AG/NIA NIH HHS/ U01 AG/AG/NIA NIH HHS/ MC_UU_/1/MRC_/Medical Research Council/United Kingdom RF1 AG/AG/NIA NIH HHS/ R35 HG/HG/NHGRI NIH HHS/ FC/WT_/Wellcome Trust/United Kingdom FC/CRUK_/Cancer Research UK/United Kingdom RF1 AG/AG/NIA NIH HHS/ WT_/Wellcome Trust/United Kingdom Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England Nat Commun. Dec 16;11(1):. doi: 10./s-020--z.I SomaScan 12/18/ Govaere O, et al. Transcriptomic profiling across the nonalcoholic fatty liver disease spectrum reveals gene signatures for steatohepatitis and fibrosis Sci Transl Med 12 572 https://www.doi.org/10./scitranslmed.aba 33,268,509 *Diabetes Mellitus, Type 2/pathology Humans Liver/pathology Liver Cirrhosis/genetics/pathology *Non-alcoholic Fatty Liver Disease/genetics/pathology Transcriptome/genetics The mechanisms that drive nonalcoholic fatty liver disease (NAFLD) remain incompletely understood. This large multicenter study characterized the transcriptional changes that occur in liver tissue across the NAFLD spectrum as disease progresses to cirrhosis to identify potential circulating markers. We performed high-throughput RNA sequencing on a discovery cohort comprising histologically characterized NAFLD samples from 206 patients. Unsupervised clustering stratified NAFLD on the basis of disease activity and fibrosis stage with differences in age, aspartate aminotransferase (AST), type 2 diabetes mellitus, and carriage of PNPLA3 rs, a genetic variant associated with NAFLD. Relative to early disease, we consistently identified 25 differentially expressed genes as fibrosing steatohepatitis progressed through stages F2 to F4. This 25-gene signature was independently validated by logistic modeling in a separate replication cohort (n = 175), and an integrative analysis with publicly available single-cell RNA sequencing data elucidated the likely relative contribution of specific intrahepatic cell populations. Translating these findings to the protein level, SomaScan analysis in more than 300 NAFLD serum samples confirmed that circulating concentrations of proteins AKR1B10 and GDF15 were strongly associated with disease activity and fibrosis stage. Supporting the biological plausibility of these data, in vitro functional studies determined that endoplasmic reticulum stress up-regulated expression of AKR1B10, GDF15, and PDGFA, whereas GDF15 supplementation tempered the inflammatory response in macrophages upon lipid loading and lipopolysaccharide stimulation. This study provides insights into the pathophysiology of progressive fibrosing steatohepatitis, and proof of principle that transcriptomic changes represent potentially tractable and clinically relevant markers of disease progression. Govaere, Olivier Cockell, Simon Tiniakos, Dina Queen, Rachel Younes, Ramy Vacca, Michele Alexander, Leigh Ravaioli, Federico Palmer, Jeremy Petta, Salvatore Boursier, Jerome Rosso, Chiara Johnson, Katherine Wonders, Kristy Day, Christopher P Ekstedt, Mattias Oresic, Matej Darlay, Rebecca Cordell, Heather J Marra, Fabio Vidal-Puig, Antonio Bedossa, Pierre Schattenberg, Jorn M Clement, Karine Allison, Michael Bugianesi, Elisabetta Ratziu, Vlad Daly, Ann K Anstee, Quentin M eng Multicenter Study Research Support, Non-U.S. Gov't Sci Transl Med. Dec 2;12(572):eaba. doi: 10./scitranslmed.aba.I SomaScan 12/04/ Schaffer M, et al. Activity of ibrutinib plus R-CHOP in diffuse large B-cell lymphoma: Response, pharmacodynamic, and biomarker analyses of a phase Ib study Cancer Treat Res Commun 25 https://www.doi.org/10./j.ctarc.. 33,188,997 Adenine/*analogs & derivatives/pharmacology/therapeutic use Antineoplastic Combined Chemotherapy Protocols/pharmacology/*therapeutic use Biomarkers, Tumor/*metabolism Cyclophosphamide/pharmacology/therapeutic use Disease-Free Survival Doxorubicin/pharmacology/therapeutic use Female Humans Lymphoma, Large B-Cell, Diffuse/*drug therapy Male Middle Aged Piperidines/pharmacology/*therapeutic use Prednisone/pharmacology/therapeutic use Prognosis Rituximab/pharmacology/therapeutic use Vincristine/pharmacology/therapeutic use Biomarkers Diffuse large b-cell lymphoma Ibrutinib Phase Ib R-chop Response to treatment INTRODUCTION: This unplanned post-hoc analysis was based on data from the phase Ib DBL study (NCT) and evaluated the association between molecular biomarkers and clinical response to combined treatment with ibrutinib plus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in diffuse large B-cell lymphoma (DLBCL) subtypes. METHODS: DLBCL subtyping was conducted using immunohistochemistry. Next-generation sequencing using immunoglobulin H primers assessed minimal residual disease (MRD). A quantitative assay evaluated Bruton's tyrosine kinase (BTK) occupancy by ibrutinib in peripheral blood mononuclear cells. Targeted DNA sequencing examined genetic variants by DLBCL subtype. Secreted protein expression was evaluated with a SomaLogic analyte panel. RESULTS: Among 21 patients with DLBCL (median age 53.5 years), 17 achieved a complete response (CR) and 4 a partial response (PR). Of the 11 subtyped patients, 9 had a CR (5/7 germinal center B-cell-like [GCB] and 4/4 non-GCB) and 2 had a PR (both GCB). Nine of 12 patients tested for MRD achieved early (cycle 2 day 1) MRD negativity; most had a CR. There was near-complete BTK occupancy at 4 h postdose. Mutation analysis (n = 19) revealed variants including CREBBP, KMT2D, LRP1B, BCL2, and TNFRSF14; only 1 CD79B and TP53 each; no CARD11 or MYD88. CONCLUSIONS: In this study, first-line ibrutinib plus R-CHOP benefited patients with DLBCL, with good overall response rate and early MRD negativity. With a caveat of small sample size, our results showed that a favorable genetic profile and younger patient age may be important to beneficial clinical outcome with ibrutinib plus R-CHOP in DLBCL. Schaffer, Michael Chaturvedi, Shalini Davis, Cuc de Jong, Jan Aquino, Regina Oki, Yasuhiro Fourneau, Nele Younes, Anas Balasubramanian, Sriram eng Clinical Trial, Phase I Research Support, Non-U.S. Gov't England Cancer Treat Res Commun. ;25:. doi: 10./j.ctarc... Epub Nov 1.I SomaScan 11/15/ Jankowski W, et al. Modified aptamers as reagents to characterize recombinant human erythropoietin products Sci Rep 10 1 https://www.doi.org/10./s-020--2 33,122,796 Aptamers, Nucleotide/*chemistry Biosimilar Pharmaceuticals/chemistry Erythropoietin/*chemistry Humans Indicators and Reagents/*chemistry Marketing/methods Protein Conformation Recombinant Proteins/*chemistry Reliable and reproducible monitoring of the conformational state of therapeutic protein products remains an unmet technological need. This need is amplified by the increasing number of biosimilars entering the drug development pipeline as many branded biologics are reaching the end of their market exclusivity period. Availability of methods to better characterize protein conformation may improve detection of counterfit and unlicensed therapeutic proteins. In this study, we report the use of a set of modified DNA aptamers with enhanced chemical diversity to probe the conformational state of 12 recombinant human erythropoietin (rHuEPO) therapeutic protein products; one FDA-licensed rHuEPO originator biological product, three rHuEPO products that are approved for marketing in the US or EU as biosimilars, and eight rHuEPO products that are not approved for marketing in the US or EU. We show that several of these modified aptamers are able to distinguish rHuEPO reference products or approved biosimilars from non-licensed rHuEPO products on the basis of differences in binding kinetics and equilibrium affinity constants. These reagents exhibit sensitivity to the conformational integrity of various forms of rHuEPO and as such represent powerful, simple-to-use analytical tools to monitor the conformational integrity of therapeutic-proteins during manufacture and to screen for and identify both substandard and counterfeit products. Jankowski, Wojciech Lagasse, H A Daniel Chang, William C McGill, Joseph Jankowska, Katarzyna I Gelinas, Amy D Janjic, Nebojsa Sauna, Zuben E eng Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. England Sci Rep. Oct 29;10(1):. doi: 10./s-020--2.I SomaScan 10/31/ Adamo L, et al. Proteomic Signatures of Heart Failure in Relation to Left Ventricular Ejection Fraction J Am Coll Cardiol 76 17 - https://www.doi.org/10./j.jacc..08.061 33,092,734 Blood Proteins/*analysis Female Heart Failure/*blood/etiology Humans Male Matched-Pair Analysis Middle Aged Myocardial Ischemia/blood *Proteomics Registries Signal Transduction *Stroke Volume Wnt Signaling Pathway heart failure left ventricular ejection fraction proteomics BACKGROUND: There is a growing recognition of the inherent limitations of the use of the left ventricular ejection fraction (LVEF) to accurately phenotype patients with heart failure (HF). OBJECTIVES: The authors sought to identify unique proteomic signatures for patients with HF with reduced ejection fraction (HFrEF), HF with a midrange LVEF (HFmrEF), and HF with preserved ejection fraction (HFpEF), as well as to identify molecular differences between patients with ischemic and nonischemic HF. METHODS: We used high-content aptamer-based proteomics technology (SOMAscan) to interrogate the blood proteome of age- and sex-matched patients with HF within different LVEF groups. RESULTS: Within the Washington University Heart Failure Registry, we identified age/sex-matched patients within 3 LVEF categories: HFrEF (LVEF 50%). We found that patients with HFrEF, HFmrEF, and HFpEF had unique variations in circulating proteins that reflected distinct biological pathophysiologies. Bioinformatics analysis revealed that there were biological themes that were unique to patients with HFrEF, HFpEF, or HFmrEF. Comparative analyses of patients with HFmrEF with improved LVEF and patients with HFmrEF with unchanged LVEF revealed marked differences between these 2 patient populations and indicated that patients with recovered LVEF are more similar to patients with HFpEF than to patients with HFrEF. Moreover, there were marked differences in the proteomic signatures of patients with ischemic and nonischemic HF. CONCLUSIONS: Viewed together, these findings suggest that it may be possible to use high-content multiplexed proteomics assays in combination with the clinical assessment of LVEF to more accurately identify clinical phenotypes of patients with HF. Adamo, Luigi Yu, Jinsheng Rocha-Resende, Cibele Javaheri, Ali Head, Richard D Mann, Douglas L eng RC2 HL/HL/NHLBI NIH HHS/ I01 BX/BX/BLRD VA/ UL1 TR/TR/NCATS NIH HHS/ K08 HL/HL/NHLBI NIH HHS/ UL1 TR/TR/NCATS NIH HHS/ U10 HL/HL/NHLBI NIH HHS/ P30 CA/CA/NCI NIH HHS/ K08 HL/HL/NHLBI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't J Am Coll Cardiol. Oct 27;76(17):-. doi: 10./j.jacc..08.061.I SomaScan 10/24/ Sathyan S, et al. Plasma proteomic profile of age, health span, and all-cause mortality in older adults Aging Cell 19 11 e https://www.doi.org/10./acel. 33,089,916 Aged Aging/*physiology Female Humans Male Mortality/*trends Plasma/cytology/*metabolism Proteomics/*methods SomaScan(R) assay aging proteomics weighted gene co-expression network analysis Aging is a complex trait characterized by a diverse spectrum of endophenotypes. By utilizing the SomaScan((R)) proteomic platform in 1,025 participants of the LonGenity cohort (age range: 65-95, 55.7% females), we found that 754 of 4,265 proteins were associated with chronological age. Pleiotrophin (PTN; beta[SE] = 0. [0.]; p = 3.21 x 10(-86) ), WNT1-inducible-signaling pathway protein 2 (WISP-2; beta[SE] = 0. [0.]; p = 4.60 x 10(-82) ), chordin-like protein 1 (CRDL1; beta[SE] = 0.[0.]; p = 1.45 x 10(-77) ), transgelin (TAGL; beta[SE] = 0. [0.]; p = 9.70 x 10(-71) ), and R-spondin-1(RSPO1; beta[SE] = 0. [0.]; p = 1.09 x 10(-70) ), were the proteins most significantly associated with age. Weighted gene co-expression network analysis identified two of nine modules (clusters of highly correlated proteins) to be significantly associated with chronological age and demonstrated that the biology of aging overlapped with complex age-associated diseases and other age-related traits. The correlation between proteomic age prediction based on elastic net regression and chronological age was 0.8 (p 1,300 proteins in 22 individuals who underwent invasive sampling. Although most of the proteins that changed significantly decreased from A to V, consistent with renal clearance, several were found to increase, the most significant of which was testican-2. To assess the clinical implications of these physiologic findings, we examined proteomic data in the Jackson Heart Study (JHS), an African-American cohort (n = 1,928), with replication in the Framingham Heart Study (FHS), a White cohort (n = 1,621). In both populations, testican-2 had a strong, positive correlation with estimated glomerular filtration rate (eGFR). In addition, higher baseline testican-2 levels were associated with a lower rate of eGFR decline in models adjusted for age, gender, hypertension, type 2 diabetes, body mass index, baseline eGFR, and albuminuria. Glomerular expression of testican-2 in human kidneys was demonstrated by immunohistochemistry, immunofluorescence, and electron microscopy, while single-cell RNA sequencing of human kidneys showed expression of the cognate gene, SPOCK2, exclusively in podocytes. In vitro, testican-2 increased glomerular endothelial tube formation and motility, raising the possibility that its secretion has a functional role within the glomerulus. Taken together, our findings identify testican-2 as a podocyte-derived biomarker of kidney health and prognosis. Ngo, Debby Wen, Donghai Gao, Yan Keyes, Michelle J Drury, Erika R Katz, Dan H Benson, Mark D Sinha, Sumita Shen, Dongxiao Farrell, Laurie A Peterson, Bennet D Friedman, David J Elmariah, Sammy Young, Bessie A Smith, J Gustav Yang, Qiong Vasan, Ramachandran S Larson, Martin G Correa, Adolfo Humphreys, Benjamin D Wang, Thomas J Pollak, Martin R Wilson, James G Gerszten, Robert E Rhee, Eugene P eng HHSNC/HL/NHLBI NIH HHS/ R01 NR/NR/NINR NIH HHS/ HHSNC/HL/NHLBI NIH HHS/ HHSNC/HL/NHLBI NIH HHS/ HHSNI/MD/NIMHD NIH HHS/ R01 HL/HL/NHLBI NIH HHS/ 75ND/HL/NHLBI NIH HHS/ U01 DK/DK/NIDDK NIH HHS/ HHSNI/HL/NHLBI NIH HHS/ R01 HL/HL/NHLBI NIH HHS/ HHSNC/HL/NHLBI NIH HHS/ N01HC/HL/NHLBI NIH HHS/ HHSNI/HB/NHLBI NIH HHS/ K08 HL/HL/NHLBI NIH HHS/ T32 DK/DK/NIDDK NIH HHS/ Research Support, N.I.H., Extramural Proc Natl Acad Sci U S A. Oct 6;117(40):-. doi: 10./pnas.. Epub Sep 21.I SomaScan 09/23/ Ganz P, et al. Proteomics for personalized cardiovascular risk assessment: in pursuit of the Holy Grail Eur Heart J 41 41 - https://www.doi.org/10./eurheartj/ehaa661 32,901,246 *Cardiovascular Diseases Heart Disease Risk Factors Humans Plasma Primary Prevention *Proteomics Risk Factors Ganz, Peter Deo, Rajat Dubin, Ruth F eng U01 DK/DK/NIDDK NIH HHS/ Comment Editorial Research Support, N.I.H., Extramural England Eur Heart J. Nov 1;41(41):-. doi: 10./eurheartj/ehaa661.I SomaScan 09/10/ Lee SJ, et al. Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight Proc Natl Acad Sci U S A 117 38 - https://www.doi.org/10./pnas. 32,900,939 Activin Receptors, Type II/genetics/metabolism Activins/*metabolism Animals Bone Resorption/*metabolism Female Male Mice Mice, Inbred C57BL Mice, Knockout Muscle, Skeletal/*metabolism Muscular Atrophy/metabolism *Myostatin/genetics/metabolism Signal Transduction *Space Flight activin bone microgravity myostatin skeletal muscle Among the physiological consequences of extended spaceflight are loss of skeletal muscle and bone mass. One signaling pathway that plays an important role in maintaining muscle and bone homeostasis is that regulated by the secreted signaling proteins, myostatin (MSTN) and activin A. Here, we used both genetic and pharmacological approaches to investigate the effect of targeting MSTN/activin A signaling in mice that were sent to the International Space Station. Wild type mice lost significant muscle and bone mass during the 33 d spent in microgravity. Muscle weights of Mstn(-/-) mice, which are about twice those of wild type mice, were largely maintained during spaceflight. Systemic inhibition of MSTN/activin A signaling using a soluble form of the activin type IIB receptor (ACVR2B), which can bind each of these ligands, led to dramatic increases in both muscle and bone mass, with effects being comparable in ground and flight mice. Exposure to microgravity and treatment with the soluble receptor each led to alterations in numerous signaling pathways, which were reflected in changes in levels of key signaling components in the blood as well as their RNA expression levels in muscle and bone. These findings have implications for therapeutic strategies to combat the concomitant muscle and bone loss occurring in people afflicted with disuse atrophy on Earth as well as in astronauts in space, especially during prolonged missions. Lee, Se-Jin Lehar, Adam Meir, Jessica U Koch, Christina Morgan, Andrew Warren, Lara E Rydzik, Renata Youngstrom, Daniel W Chandok, Harshpreet George, Joshy Gogain, Joseph Michaud, Michael Stoklasek, Thomas A Liu, Yewei Germain-Lee, Emily L eng R01 AG/AG/NIA NIH HHS/ R01 AR/AR/NIAMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Proc Natl Acad Sci U S A. Sep 22;117(38):-. doi: 10./pnas.. Epub Sep 8.I SomaScan 09/10/ Chan MY, et al. Prioritizing Candidates of Post-Myocardial Infarction Heart Failure Using Plasma Proteomics and Single-Cell Transcriptomics Circulation 142 15 - https://www.doi.org/10./CIRCULATIONAHA.119. 32,885,678 Aged Aged, 80 and over Animals Blood Proteins/*biosynthesis Female *Gene Expression Profiling *Gene Expression Regulation *Heart Failure/blood/genetics Humans Male Mice Middle Aged *Myocardial Infarction/blood/complications *Proteomics *Single-Cell Analysis heart failure myocardial infarction proteomics transcriptome BACKGROUND: Heart failure (HF) is the most common long-term complication of acute myocardial infarction (MI). Understanding plasma proteins associated with post-MI HF and their gene expression may identify new candidates for biomarker and drug target discovery. METHODS: We used aptamer-based affinity-capture plasma proteomics to measure plasma proteins at 1 month post-MI in a New Zealand cohort (CDCS [Coronary Disease Cohort Study]) including 181 patients post-MI who were subsequently hospitalized for HF in comparison with 250 patients post-MI who remained event free over a median follow-up of 4.9 years. We then correlated plasma proteins with left ventricular ejection fraction measured at 4 months post-MI and identified proteins potentially coregulated in post-MI HF using weighted gene co-expression network analysis. A Singapore cohort (IMMACULATE [Improving Outcomes in Myocardial Infarction through Reversal of Cardiac Remodelling]) of 223 patients post-MI, of which 33 patients were hospitalized for HF (median follow-up, 2.0 years), was used for further candidate enrichment of plasma proteins by using Fisher meta-analysis, resampling-based statistical testing, and machine learning. We then cross-referenced differentially expressed proteins with their differentially expressed genes from single-cell transcriptomes of nonmyocyte cardiac cells isolated from a murine MI model, and single-cell and single-nucleus transcriptomes of cardiac myocytes from murine HF models and human patients with HF. RESULTS: In the CDCS cohort, 212 differentially expressed plasma proteins were significantly associated with subsequent HF events. Of these, 96 correlated with left ventricular ejection fraction measured at 4 months post-MI. Weighted gene co-expression network analysis prioritized 63 of the 212 proteins that demonstrated significantly higher correlations among patients who developed post-MI HF in comparison with event-free controls (data set 1). Cross-cohort meta-analysis of the IMMACULATE cohort identified 36 plasma proteins associated with post-MI HF (data set 2), whereas single-cell transcriptomes identified 15 gene-protein candidates (data set 3). The majority of prioritized proteins were of matricellular origin. The 6 most highly enriched proteins that were common to all 3 data sets included well-established biomarkers of post-MI HF: N-terminal B-type natriuretic peptide and troponin T, and newly emergent biomarkers, angiopoietin-2, thrombospondin-2, latent transforming growth factor-beta binding protein-4, and follistatin-related protein-3, as well. CONCLUSIONS: Large-scale human plasma proteomics, cross-referenced to unbiased cardiac transcriptomics at single-cell resolution, prioritized protein candidates associated with post-MI HF for further mechanistic and clinical validation. Chan, Mark Y Efthymios, Motakis Tan, Sock Hwee Pickering, John W Troughton, Richard Pemberton, Christopher Ho, Hee-Hwa Prabath, Joseph-Francis Drum, Chester L Ling, Lieng Hsi Soo, Wern-Miin Chai, Siang-Chew Fong, Alan Oon, Yen-Yee Loh, Joshua P Lee, Chi-Hang Foo, Roger S Y Ackers-Johnson, Matthew Andrew Pilbrow, Anna Richards, A Mark eng Clinical Trial Multicenter Study Research Support, Non-U.S. Gov't Circulation. Oct 13;142(15):-. doi: 10./CIRCULATIONAHA.119.. Epub Sep 4.I SomaScan 09/05/ Moin ASM, et al. Renin-Angiotensin System overactivation in polycystic ovary syndrome, a risk for SARS-CoV-2 infection? Metabol Open 7 https://www.doi.org/10./j.metop.. 32,838,280 ACE2 protein Angiotensinogen Polycystic ovary syndrome Renin BACKGROUND: The SARS-CoV-2 coronavirus gains entry to target cells via the angiotensin-converting enzyme 2 (ACE2) receptor present on cells in blood vessels, lungs, heart, intestines, and kidneys. Renin-Angiotensin System (RAS) overactivity has also been described in metabolic syndrome, type 2 diabetes (T2D) and obesity, conditions shared by women with polycystic ovary syndrome (PCOS) We hypothesized that RAS overactivity may be present in PCOS. METHODS: We determined plasma levels of RAS-related proteins in a cohort of age matched control women (n = 97) and women with PCOS (n = 146). Plasma levels of RAS-related proteins (ACE2, Renin and Angiotensinogen (AGT)) were determined by Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement. RESULTS: PCOS women had a higher BMI (p 8% body weight following a low-caloric diet (LCD, 800 kcal/d for 8 weeks). The two groups were comparable at baseline for body composition, glycemic control, adipose tissue transcriptomics and plasma ketone bodies. But they differed significantly in their response to LCD, including improvements in visceral fat, overall insulin resistance (IR) and tissue-specific IR. Transcriptomics analyses found down-regulation in key lipogenic genes (e.g. SCD, ELOVL5) in responders relative to non-responders; metabolomics showed increase in ketone bodies; while proteomics revealed differences in lipoproteins. Findings were consistent between genders; with women displaying smaller improvements owing to a better baseline metabolic condition. Integrative analyses identified a plasma omics model that was able to predict non-responders with strong performance (on a testing dataset, the Receiving Operating Curve Area Under the Curve (ROC AUC) was 75% with 95% Confidence Intervals (CI) [67%, 83%]). This model was based on baseline parameters without the need for intrusive measurements and outperformed clinical models (p = 0., with a +14% difference on the ROC AUCs). Our approach document differences between responders and non-responders, with strong contributions from liver and adipose tissues. Differences may be due to de novo lipogenesis, keto-metabolism and lipoprotein metabolism. These findings are useful for clinical practice to better characterize non-responders both prior and during weight loss. Valsesia, Armand Chakrabarti, Anirikh Hager, Jorg Langin, Dominique Saris, Wim H M Astrup, Arne Blaak, Ellen E Viguerie, Nathalie Masoodi, Mojgan eng Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't England Sci Rep. Jun 8;10(1):. doi: 10./s-020--8.I SomaScan 06/10/ Rashid MU, et al. Zika virus dysregulates human Sertoli cell proteins involved in spermatogenesis with little effect on tight junctions PLoS Negl Trop Dis 14 6 e https://www.doi.org/10./journal.pntd. 32,511,241 Animals Chlorocebus aethiops Humans Male Proteomics Semen/virology Sertoli Cells/*immunology/virology Signal Transduction *Spermatogenesis Tight Junctions/*immunology/virology Vero Cells Virus Replication Zika Virus Zika Virus Infection/*immunology Zika virus (ZIKV), a neglected tropical disease until its re-emergence in , causes microcephaly in infants and Guillain-Barre syndrome in adults. Its re-emergence and spread to more than 80 countries led the World Health Organization in to declare a Public Health Emergency. ZIKV is mainly transmitted by mosquitos, but can persist in infected human male semen for prolonged periods and may be sexually transmitted. Testicular Sertoli cells support ZIKV replication and may be a reservoir for persistent ZIKV infection. Electrical impedance analyses indicated ZIKV infection rapidly disrupted Vero cell monolayers but had little effect upon human Sertoli cells (HSerC). We determined ZIKV-induced proteomic changes in HSerC using an aptamer-based multiplexed technique (SOMAscan) targeting > human proteins. ZIKV infection caused differential expression of 299 proteins during three different time points, including 5 days after infection. Dysregulated proteins are involved in different bio-functions, including cell death and survival, cell cycle, maintenance of cellular function, cell signaling, cellular assembly, morphology, movement, molecular transport, and immune response. Many signaling pathways important for maintenance of HSerC function and spermatogenesis were highly dysregulated. These included IL-6, IGF1, EGF, NF-kappaB, PPAR, ERK/MAPK, and growth hormone signaling. Down-regulation of the PPAR signaling pathway might impact cellular energy supplies. Upstream molecule analysis also indicated microRNAs involved in germ cell development were downregulated by infection. Overall, this study leads to a better understanding of Sertoli cellular mechanisms used by ZIKV during persistent infection and possible ZIKV impacts on spermatogenesis. Rashid, Mahamud-Ur Zahedi-Amiri, Ali Glover, Kathleen K M Gao, Ang Nickol, Michaela E Kindrachuk, Jason Wilkins, John A Coombs, Kevin M eng 950-/CIHR/Canada Research Support, Non-U.S. Gov't PLoS Negl Trop Dis. Jun 8;14(6):e. doi: 10./journal.pntd.. eCollection Jun.I SomaScan 06/09/ Ruffieux H, et al. A fully joint Bayesian quantitative trait locus mapping of human protein abundance in plasma PLoS Comput Biol 16 6 e https://www.doi.org/10./journal.pcbi. 32,492,067 *Bayes Theorem Biomarkers/blood Blood Proteins/*genetics Genome-Wide Association Study Humans *Quantitative Trait Loci Molecular quantitative trait locus (QTL) analyses are increasingly popular to explore the genetic architecture of complex traits, but existing studies do not leverage shared regulatory patterns and suffer from a large multiplicity burden, which hampers the detection of weak signals such as trans associations. Here, we present a fully multivariate proteomic QTL (pQTL) analysis performed with our recently proposed Bayesian method LOCUS on data from two clinical cohorts, with plasma protein levels quantified by mass-spectrometry and aptamer-based assays. Our two-stage study identifies 136 pQTL associations in the first cohort, of which >80% replicate in the second independent cohort and have significant enrichment with functional genomic elements and disease risk loci. Moreover, 78% of the pQTLs whose protein abundance was quantified by both proteomic techniques are confirmed across assays. Our thorough comparisons with standard univariate QTL mapping on (1) these data and (2) synthetic data emulating the real data show how LOCUS borrows strength across correlated protein levels and markers on a genome-wide scale to effectively increase statistical power. Notably, 15% of the pQTLs uncovered by LOCUS would be missed by the univariate approach, including several trans and pleiotropic hits with successful independent validation. Finally, the analysis of extensive clinical data from the two cohorts indicates that the genetically-driven proteins identified by LOCUS are enriched in associations with low-grade inflammation, insulin resistance and dyslipidemia and might therefore act as endophenotypes for metabolic diseases. While considerations on the clinical role of the pQTLs are beyond the scope of our work, these findings generate useful hypotheses to be explored in future research; all results are accessible online from our searchable database. Thanks to its efficient variational Bayes implementation, LOCUS can analyze jointly thousands of traits and millions of markers. Its applicability goes beyond pQTL studies, opening new perspectives for large-scale genome-wide association and QTL analyses. Diet, Obesity and Genes (DiOGenes) trial registration number: NCT. Ruffieux, Helene Carayol, Jerome Popescu, Radu Harper, Mary-Ellen Dent, Robert Saris, Wim H M Astrup, Arne Hager, Jorg Davison, Anthony C Valsesia, Armand eng MC_UU_/10/MRC_/Medical Research Council/United Kingdom Research Support, Non-U.S. Gov't PLoS Comput Biol. Jun 3;16(6):e. doi: 10./journal.pcbi.. eCollection Jun.I SomaScan 06/04/ Demidowich AP, et al. Colchicine's effects on metabolic and inflammatory molecules in adults with obesity and metabolic syndrome: results from a pilot randomized controlled trial Int J Obes (Lond) 44 8 - https://www.doi.org/10./s-020--3 32,461,554 Adult Anti-Inflammatory Agents/pharmacology/*therapeutic use Betacoronavirus/drug effects C-Reactive Protein Covid-19 Colchicine/pharmacology/*therapeutic use Coronavirus Infections/drug therapy/*immunology Double-Blind Method Female Humans Interleukin-6 Male Metabolic Syndrome/*complications/drug therapy/*immunology Middle Aged Obesity/complications/drug therapy/*immunology Pandemics Pilot Projects Pneumonia, Viral/drug therapy/*immunology SARS-CoV-2 Treatment Outcome Young Adult OBJECTIVE: Recent clinical trials have demonstrated that colchicine may have metabolic and cardiovascular and benefits in at-risk patients; however, the mechanisms through which colchicine may improve outcomes are still unclear. We sought to examine colchicine's effects on circulating inflammatory and metabolic molecules in adults with obesity and metabolic syndrome (MetS). METHODS: Blood samples were collected pre- and post-intervention during a double-blind randomized controlled trial in which 40 adults with obesity and MetS were randomized to colchicine 0.6 mg or placebo twice-daily for 3 months. Serum samples were analyzed for circulating factors using the SomaScan Platform. The Benjamini-Hochberg procedure was used to adjust the false discovery rate (FDR) for multiple testing. RESULTS: At baseline, age (48.0 +/- 13.8 vs. 44.7 +/- 10.3 years) and BMI (39.8 +/- 6.4 vs. 41.8 +/- 8.2 kg/m(2)) were not different between groups. After controlling for the FDR, 34 molecules were significantly changed by colchicine. Colchicine decreased concentrations of multiple inflammatory molecules, including C-reactive protein, interleukin 6, and resistin, in addition to vascular-related proteins (e.g., oxidized low-density lipoprotein receptor, phosphodiesterase 5A). Conversely, relative to placebo, colchicine significantly increased concentrations of eight molecules including secreted factors associated with metabolism and anti-thrombosis. CONCLUSIONS: In adults with obesity, colchicine significantly affected concentrations of proteins involved in the innate immune system, endothelial function and atherosclerosis, uncovering new mechanisms behind its cardiometabolic effects. Further research is warranted to investigate whether colchicine's IL-6 suppressive effects may be beneficial in COVID-19. Demidowich, Andrew P Levine, Jordan A Apps, Richard Cheung, Foo K Chen, Jinguo Fantoni, Giovanna Patel, Tushar P Yanovski, Jack A eng ZIA HD/ImNIH/Intramural NIH HHS/ Randomized Controlled Trial England Int J Obes (Lond). Aug;44(8):-. doi: 10./s-020--3. Epub May 27.I SomaScan 05/29/ Walker ME, et al. Proteomic and Metabolomic Correlates of Healthy Dietary Patterns: The Framingham Heart Study Nutrients 12 5 https://www.doi.org/10./nu 32,438,708 Cross-Sectional Studies Diet Surveys Diet, Healthy/*statistics & numerical data Diet, Mediterranean/*statistics & numerical data Dietary Approaches To Stop Hypertension/*statistics & numerical data Eating/*physiology Female Humans Linear Models Longitudinal Studies Male *Metabolome Metabolomics Middle Aged Proteome/*analysis Proteomics biomarker diet quality dietary patterns metabolomic proteomic Data on proteomic and metabolomic signatures of healthy dietary patterns are limited. We evaluated the cross-sectional association of serum proteomic and metabolomic markers with three dietary patterns: the Alternative Healthy Eating Index (AHEI), the Dietary Approaches to Stop Hypertension (DASH) diet; and a Mediterranean-style (MDS) diet. We examined participants from the Framingham Offspring Study (mean age; 55 years; 52% women) who had complete proteomic (n = ) and metabolomic (n = ) data; using food frequency questionnaires to derive dietary pattern indices. Proteins and metabolites were quantified using the SomaScan platform and liquid chromatography/tandem mass spectrometry; respectively. We used multivariable-adjusted linear regression models to relate each dietary pattern index (independent variables) to each proteomic and metabolomic marker (dependent variables). Of the proteins; 103 were associated with at least one dietary pattern (48 with AHEI; 83 with DASH; and 8 with MDS; all false discovery rate [FDR] = 0.05). We identified unique associations between dietary patterns and proteins (17 with AHEI; 52 with DASH; and 3 with MDS; all FDR = 0.05). Significant proteins enriched biological pathways involved in cellular metabolism/proliferation and immune response/inflammation. Of the 216 metabolites; 65 were associated with at least one dietary pattern (38 with AHEI; 43 with DASH; and 50 with MDS; all FDR = 0.05). All three dietary patterns were associated with a common signature of 24 metabolites (63% lipids). Proteins and metabolites associated with dietary patterns may help characterize intermediate phenotypes that provide insights into the molecular mechanisms mediating diet-related disease. Our findings warrant replication in independent populations. Walker, Maura E Song, Rebecca J Xu, Xiang Gerszten, Robert E Ngo, Debby Clish, Clary B Corlin, Laura Ma, Jiantao Xanthakis, Vanessa Jacques, Paul F Vasan, Ramachandran S eng P30 DK/DK/NIDDK NIH HHS/ HHSNI/HL/NHLBI NIH HHS/ P30 DK/HL/NHLBI NIH HHS/ 75ND/HL/NHLBI NIH HHS/ P20 HL/HL/NHLBI NIH HHS/ R01 HL/HL/NHLBI NIH HHS/ P30 DK/DK/NIDDK NIH HHS/ U01 AG/AG/NIA NIH HHS/ 5T32HL/HL/NHLBI NIH HHS/ RF1 AG/AG/NIA NIH HHS/ Evaluation Study Switzerland Nutrients. May 19;12(5):. doi: 10./nu.I SomaScan 05/23/ Ahmad S, et al. CDH6 and HAGH protein levels in plasma associate with Alzheimer's disease in APOE epsilon4 carriers Sci Rep 10 1 https://www.doi.org/10./s-020--5 32,427,856 Alzheimer Disease/*metabolism Apolipoprotein E4/genetics/*metabolism Biomarkers/blood Cadherins/*metabolism *Genetic Carrier Screening Humans Thiolester Hydrolases/*metabolism Many Alzheimer's disease (AD) genes including Apolipoprotein E (APOE) are found to be expressed in blood-derived macrophages and thus may alter blood protein levels. We measured 91 neuro-proteins in plasma from 316 participants of the Rotterdam Study (incident AD = 161) using Proximity Extension Ligation assay. We studied the association of plasma proteins with AD in the overall sample and stratified by APOE. Findings from the Rotterdam study were replicated in 186 AD patients of the BioFINDER study. We further evaluated the correlation of these protein biomarkers with total tau (t-tau), phosphorylated tau (p-tau) and amyloid-beta (Abeta) 42 levels in cerebrospinal fluid (CSF) in the Amsterdam Dementia Cohort (N = 441). Finally, we conducted a genome-wide association study (GWAS) to identify the genetic variants determining the blood levels of AD-associated proteins. Plasma levels of the proteins, CDH6 (beta = 0.638, P = 3.33 x 10(-4)) and HAGH (beta = 0.481, P = 7.20 x 10(-4)), were significantly elevated in APOE epsilon4 carrier AD patients. The findings in the Rotterdam Study were replicated in the BioFINDER study for both CDH6 (beta = 1.365, P = 3.97 x 10(-3)) and HAGH proteins (beta = 0.506, P = 9.31 x 10(-7)) when comparing cases and controls in APOE epsilon4 carriers. In the CSF, CDH6 levels were positively correlated with t-tau and p-tau in the total sample as well as in APOE epsilon4 stratum (P =15 vs OAHI human lung cell proteins affected by the different IAV strains, and identified more than 500 significantly dysregulated cellular proteins. Our analyses indicated that the avian strains induced more profound changes in the A549 global proteome compared to all tested low-pathogenicity H1N1 strains. The PR8 strain induced a general activation, primarily by upregulating many immune molecules, the seasonal RV733 and pdm09 strains had minimal effect upon assayed molecules, and the avian strains induced significant downregulation, primarily in antimicrobial response, cardiovascular and post-translational modification systems. Coombs, Kevin M Simon, Philippe F McLeish, Nigel J Zahedi-Amiri, Ali Kobasa, Darwyn eng MOP-/CIHR/Canada Research Support, Non-U.S. Gov't Switzerland Viruses. Nov 5;11(11):. doi: 10./v.I SomaScan 11/07/ Alexaki A, et al. Effects of codon optimization on coagulation factor IX translation and structure: Implications for protein and gene therapies Sci Rep 9 1 https://www.doi.org/10./s-019--2 31,664,102 *Codon Factor IX/*chemistry/*genetics Genetic Code *Genetic Therapy HEK293 Cells Humans *Protein Biosynthesis Protein Conformation Synonymous codons occur with different frequencies in different organisms, a phenomenon termed codon usage bias. Codon optimization, a common term for a variety of approaches used widely by the biopharmaceutical industry, involves synonymous substitutions to increase protein expression. It had long been presumed that synonymous variants, which, by definition, do not alter the primary amino acid sequence, have no effect on protein structure and function. However, a critical mass of reports suggests that synonymous codon variations may impact protein conformation. To investigate the impact of synonymous codons usage on protein expression and function, we designed an optimized coagulation factor IX (FIX) variant and used multiple methods to compare its properties to the wild-type FIX upon expression in HEK293T cells. We found that the two variants differ in their conformation, even when controlling for the difference in expression levels. Using ribosome profiling, we identified robust changes in the translational kinetics of the two variants and were able to identify a region in the gene that may have a role in altering the conformation of the protein. Our data have direct implications for codon optimization strategies, for production of recombinant proteins and gene therapies. Alexaki, Aikaterini Hettiarachchi, Gaya K Athey, John C Katneni, Upendra K Simhadri, Vijaya Hamasaki-Katagiri, Nobuko Nanavaty, Puja Lin, Brian Takeda, Kazuyo Freedberg, Daron Monroe, Dougald McGill, Joseph R Peters, Robert Kames, Jacob M Holcomb, David D Hunt, Ryan C Sauna, Zuben E Gelinas, Amy Janjic, Nebojsa DiCuccio, Michael Bar, Haim Komar, Anton A Kimchi-Sarfaty, Chava eng R15 HL/HL/NHLBI NIH HHS/ HL/U.S. Department of Health & Human Services | NIH | Office of Extramural Research, National Institutes of Health (OER)/International Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. England Sci Rep. Oct 29;9(1):. doi: 10./s-019--2.I SomaScan 10/31/ Kukova LZ, et al. Comparison of Urine and Plasma Biomarker Concentrations Measured by Aptamer-Based versus Immunoassay Methods in Cardiac Surgery Patients J Appl Lab Med 4 3 331-342 https://www.doi.org/10./jalm.. 31,659,071 Aged Biomarkers/*blood/*urine Cardiac Surgical Procedures Comorbidity Female Heart Diseases/*blood/diagnosis/surgery/*urine Humans Immunoassay/*methods/*standards Male Middle Aged BACKGROUND: Protein detection assays are invaluable tools in the field of biomarker discovery. However, only immunoassays are widely used and can measure 10-20 analytes per biosample. The novel SOMAmer-based assay uses nucleotide aptamer technology to measure over analytes per biosample. We compared the SOMAmer-based platform to traditional approaches to quantify analytes in a clinical setting with paired samples before and after cardiac surgery. METHODS: In a substudy of the Translational Research Investigating Biomarker Endpoints in Acute Kidney Injury cohort, 54 individuals with acute kidney injury after cardiac surgery were identified. Preoperative and postoperative plasma and urine samples that had been previously evaluated for biomarker concentrations via immunoassays were analyzed via SOMAmer-based assay. RESULTS: Spearman correlations were estimated when >50% of biomarker values were within detectable ranges by immunoassay (plasma biomarkers: preoperative, 26/33; postoperative, 31/33; urine biomarkers: preoperative, 13/16; postoperative, 16/16). Overall, 27% of reportable plasma preoperative biomarkers displayed correlations >/=0.75 between immunoassay and SOMAmer measurements; 23% displayed correlations of 0.50-0.75, and 50% displayed correlations /=0.75, 16% displayed correlations 0.50-0.75, and 42% displayed correlations 1 muM). Conversely, we identified one SOMAmer reagent for GDF-8 from one of the modified libraries that demonstrated excellent affinity (K(d) = 0.23 nM) and specificity. In contrast, standard protocols that utilized only positive selection produced binding reagents with similar affinity for both proteins. High affinity and specificity were efficiently encoded in minimal sequences of 21 nucleotides for GDF-11 and 24 nucleotides for GDF-8. Further characterization in pull-down, competition, sandwich-binding, and kinetic studies revealed robust binding under a wide range of buffer and assay conditions. For highly similar proteins like GDF-11 and GDF-8, our method of selection coupled with counter-selection was essential for identification of high-affinity, specific reagents that have the potential to elucidate the fundamental distinction of these growth factors in biology. Ochsner, Urs A Green, Louis S Rice, Taylor P Olivas, Edgar Janjic, Nebojsa Katilius, Evaldas eng Biochemistry. Nov 19;58(46):-. doi: 10./acs.biochem.9b. Epub Nov 7.I SomaScan 10/23/ Tin A, et al. Reproducibility and Variability of Protein Analytes Measured Using a Multiplexed Modified Aptamer Assay J Appl Lab Med 4 1 30-39 https://www.doi.org/10./jalm.. 31,639,705 Aged Atherosclerosis/*blood/diagnosis Blood Proteins/*analysis Equipment Design Female Glomerular Filtration Rate/physiology Humans Male Middle Aged Prospective Studies Proteomics/*instrumentation Reproducibility of Results BACKGROUND: There is growing interest in the use of multiplexed aptamer-based assays for large-scale proteomic studies. However, the analytic, short- and long-term variation of the measured proteins is largely uncharacterized. METHODS: We quantified plasma protein analytes from 42 participants in the Atherosclerosis Risk in Communities (ARIC) Study in split samples and at multiple visits using a multiplexed modified aptamer assay. We calculated the CV, Spearman correlation, and intraclass correlation (ICC) between split samples and evaluated the short-term (4-9 weeks) and long-term (approximately 20 years) variability using paired t-tests with log-transformed protein concentrations and Bonferroni-corrected significance thresholds. We performed principal component (PC) analysis of protein analyte concentrations and evaluated their associations with age, sex, race, and estimated glomerular filtration rate (eGFR). RESULTS: The mean baseline age was 57 years at the first visit, 43% of participants were male and 57% were white. Among protein analytes that passed quality control, half (n = ) had CVs 0.89, and ICCs > 0.96 among the split samples. Over the short term, only 1 analyte had a statistically significant difference between the 2 time points, whereas, over approximately 20 years, 866 analytes (23.4%) had statistically significant differences (P /=1.2, P /=50 years of type 1 diabetes. Specifically, pyruvate kinase M2 (PKM2) activation protected insulin-deficient diabetic mice from hyperglycemia-induced glomerular pathology. This study aims to extend these findings in a separate cohort of individuals with type 1 and type 2 diabetes and discover new circulatory biomarkers for renal protection through proteomics and metabolomics of Medalists' plasma. We hypothesize that increased glycolytic flux and improved mitochondrial biogenesis will halt the progression of diabetic nephropathy. RESEARCH DESIGN AND METHODS: Immunoblots analyzed selected glycolytic and mitochondrial enzymes in postmortem glomeruli of non-Medalists with type 1 diabetes (n = 15), type 2 diabetes (n = 19), and no diabetes (n = 5). Plasma proteomic (SOMAscan) (n = 180) and metabolomic screens (n = 214) of Medalists with and without stage 3b chronic kidney disease (CKD) were conducted and significant markers validated by ELISA. RESULTS: Glycolytic (PKM1, PKM2, and ENO1) and mitochondrial (MTCO2) enzymes were significantly elevated in glomeruli of CKD- versus CKD+ individuals with type 2 diabetes. Medalists' plasma PKM2 correlated with estimated glomerular filtration rate (r (2) = 0.077; P = 0.). Several glucose and mitochondrial enzymes in circulation were upregulated with corresponding downregulation of toxic metabolites in CKD-protected Medalists. Amyloid precursor protein was also significantly upregulated, tumor necrosis factor receptors downregulated, and both confirmed by ELISA. CONCLUSIONS: Elevation of enzymes involved in the metabolism of intracellular free glucose and its metabolites in renal glomeruli is connected to preserving kidney function in both type 1 and type 2 diabetes. The renal profile of elevated glycolytic enzymes and reduced toxic glucose metabolites is reflected in the circulation, supporting their use as biomarkers for endogenous renal protective factors in people with diabetes. Gordin, Daniel Shah, Hetal Shinjo, Takanori St-Louis, Ronald Qi, Weier Park, Kyoungmin Paniagua, Samantha M Pober, David M Wu, I-Hsien Bahnam, Vanessa Brissett, Megan J Tinsley, Liane J Dreyfuss, Jonathan M Pan, Hui Dong, Yutong Niewczas, Monika A Amenta, Peter Sadowski, Thorsten Kannt, Aimo Keenan, Hillary A King, George L eng DP3 DK/DK/NIDDK NIH HHS/ T32 DK/DK/NIDDK NIH HHS/ P30 DK/DK/NIDDK NIH HHS/ R24 DK/DK/NIDDK NIH HHS/ DP3 DK/DK/NIDDK NIH HHS/ UL1 RR/RR/NCRR NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Diabetes Care. Jul;42(7):-. doi: 10./dc18-. Epub May 10.I SomaScan 05/12/ Wells QS, et al. Accelerating Biomarker Discovery Through Electronic Health Records, Automated Biobanking, and Proteomics J Am Coll Cardiol 73 17 - https://www.doi.org/10./j.jacc..01.074 31,047,008 Academic Medical Centers Acceleration Aged Automation/*methods Biological Specimen Banks/organization & administration Biomarkers/blood Cohort Studies Electronic Health Records/*organization & administration Female Heart Failure/*blood/diagnosis Humans Male Middle Aged Proportional Hazards Models Prospective Studies Proteomics/*organization & administration Reproducibility of Results Risk Assessment Sensitivity and Specificity Thrombospondins/*blood biomarkers electronic health records heart failure proteomics BACKGROUND: Circulating biomarkers can facilitate diagnosis and risk stratification for complex conditions such as heart failure (HF). Newer molecular platforms can accelerate biomarker discovery, but they require significant resources for data and sample acquisition. OBJECTIVES: The purpose of this study was to test a pragmatic biomarker discovery strategy integrating automated clinical biobanking with proteomics. METHODS: Using the electronic health record, the authors identified patients with and without HF, retrieved their discarded plasma samples, and screened these specimens using a DNA aptamer-based proteomic platform (1,129 proteins). Candidate biomarkers were validated in 3 different prospective cohorts. RESULTS: In an automated manner, plasma samples from 1,315 patients (31% with HF) were collected. Proteomic analysis of a 96-patient subset identified 9 candidate biomarkers (p human astrocyte cell proteins. We identified almost 300 astrocyte proteins significantly dysregulated by ZIKV infection that span diverse functions and signaling pathways, including protein translation, synaptic control, cell migration and differentiation. Sher, Affan A Glover, Kathleen K M Coombs, Kevin M eng Switzerland Front Microbiol. Mar 26;10:596. doi: 10./fmicb... eCollection .I SomaScan 04/16/ Mulla CM, et al. Plasma FGF-19 Levels are Increased in Patients with Post-Bariatric Hypoglycemia Obes Surg 29 7 - https://www.doi.org/10./s-019--0 30,976,983 Adult Bariatric Surgery/*adverse effects Blood Glucose/metabolism Blood Proteins/analysis/metabolism Case-Control Studies Female Fibroblast Growth Factors/*blood Gastric Bypass/adverse effects Gastrointestinal Hormones/blood Glucagon-Like Peptide 1/blood Glucagon-Like Peptide-1 Receptor/antagonists & inhibitors Humans Hypoglycemia/*blood/diet therapy/drug therapy/*etiology Male Meals Middle Aged Obesity, Morbid/blood/*surgery Peptide Fragments/therapeutic use Postoperative Complications/*blood/diet therapy/drug therapy Proteome/analysis Proteomics Up-Regulation Bile acids Fgf-19 Gastric bypass Hypoglycemia Pharmaceuticals, has received investigator-initiated grant support from Janssen Pharmaceuticals, Medimmune, Sanofi, Astra-Zeneca, Jenesis, and Nuclea, has been a site investigator for XOMA, and acknowledges clinical trial research trial product support from Ethicon, Covidien, NovoNordisk, Nestle, and Dexcom within the past 5 years. Dr. Patti and Dr. Goldfine disclose a patent application for plasma proteins contributing to hypoglycemia. Dr. Mulla, Dr. Dreyfuss, Dr. Houten, Dr. Pan, Dr. Pober, Dr. Wewer Albrechtsen, Dr. Svane, Dr. Schmidt, Dr. Holst, Dr. Craig and Dr. McLaughlin declare no potential competing interests. BACKGROUND: Hypoglycemia is an increasingly recognized complication of bariatric surgery. Mechanisms contributing to glucose lowering remain incompletely understood. We aimed to identify differentially abundant plasma proteins in patients with post-bariatric hypoglycemia (PBH) after Roux-en-Y gastric bypass (RYGB), compared to asymptomatic post-RYGB. METHODS: Proteomic analysis of blood samples collected after overnight fast and mixed meal challenge in individuals with PBH, asymptomatic RYGB, severe obesity, or overweight recruited from outpatient hypoglycemia or bariatric clinics. RESULTS: The top-ranking differentially abundant protein at 120 min after mixed meal was fibroblast growth factor 19 (FGF-19), an intestinally derived hormone regulated by bile acid-FXR signaling; levels were 2.4-fold higher in PBH vs. asymptomatic post-RYGB (mean + SEM, +/- 141 vs. 428 +/- 45, P host proteins to detect ZIKV-induced host protein dysregulation at multiple time points during infection. A total of 125 Vero cell host proteins, including cytokines such as CXCL11 and CCL5, interferon stimulated gene 15, and translation initiation factors EIF5A and EIF4G2, are significantly dysregulated after ZIKV infection. Bioinformatic analyses of 77 host proteins, that are significantly dysregulated >/=1.25-fold, identify several activated biological processes, including the JAK/STAT, Tec kinase, and complement cascade pathways. Glover, Kathleen K M Gao, Ang Zahedi-Amiri, Ali Coombs, Kevin M eng CIHR/Canada Research Support, Non-U.S. Gov't Germany Proteomics. Feb;19(4):e. doi: 10./pmic.. Epub Jan 23.I SomaScan 12/24/ Mysona D, et al. A combined score of clinical factors and serum proteins can predict time to recurrence in high grade serous ovarian cancer Gynecol Oncol 152 3 574-580 https://www.doi.org/10./j.ygyno..12.015 30,578,005 Cystadenocarcinoma, Serous/*blood/pathology/surgery Cytoreduction Surgical Procedures Disease-Free Survival Female Humans Middle Aged Neoplasm Grading Neoplasm Proteins/*blood Neoplasm Recurrence, Local/*blood/pathology Ovarian Neoplasms/*blood/pathology/surgery Predictive Value of Tests Progression-Free Survival Prospective Studies Biomarkers Ovarian neoplasm Prognosis Serum proteomics OBJECTIVE: To investigate the utility of a combined panel of protein biomarkers and clinical factors to predict recurrence in serous ovarian cancer patients. METHODS: Women at Augusta University diagnosed with ovarian cancer were enrolled between and (n_=_71). Blood was drawn at enrollment and follow-up visits. Patient serum collected at remission was analyzed using the SOMAscan array (n_=_35) to measure levels of proteins. The best 26 proteins were confirmed using Luminex assays in the same 35 patients and in an additional 36 patients (n(total)_=_71) as orthogonal validation. The data from these 26 proteins was combined with clinical factors using an elastic net multivariate model to find an optimized combination predictive of progression-free survival (PFS). RESULTS: Of the 26 proteins, Brain Derived Neurotrophic Factor and Platelet Derived Growth Factor molecules were significant for predicting PFS on both univariate and multivariate analyses. All 26 proteins were combined with clinical factors using the elastic net algorithm. Ten components were determined to predict PFS (HR of 6.55, p-value 1.12_x_10(-6), CI 2.57-16.71). This model was named the serous high grade ovarian cancer (SHOC) score. CONCLUSION: The SHOC score can predict patient prognosis in remission. This tool will hopefully lead to early intervention and consolidation therapy strategies in remission patients destined to recur. Mysona, David Pyrzak, Adam Purohit, Sharad Zhi, Wenbo Sharma, Ashok Tran, Lynn Tran, Paul Bai, Shan Rungruang, Bunja Ghamande, Sharad She, Jin-Xiong eng F30 DK/DK/NIDDK NIH HHS/ Observational Study Research Support, Non-U.S. Gov't Gynecol Oncol. Mar;152(3):574-580. doi: 10./j.ygyno..12.015. Epub Dec 18.I SomaScan 12/24/ Ghaemi MS, et al. Multiomics modeling of the immunome, transcriptome, microbiome, proteome and metabolome adaptations during human pregnancy Bioinformatics 35 1 95-103 https://www.doi.org/10./bioinformatics/bty537 30,561,547 Computational Biology Female Humans *Metabolome *Microbiota *Pregnancy *Proteome *Transcriptome MOTIVATION: Multiple biological clocks govern a healthy pregnancy. These biological mechanisms produce immunologic, metabolomic, proteomic, genomic and microbiomic adaptations during the course of pregnancy. Modeling the chronology of these adaptations during full-term pregnancy provides the frameworks for future studies examining deviations implicated in pregnancy-related pathologies including preterm birth and preeclampsia. RESULTS: We performed a multiomics analysis of 51 samples from 17 pregnant women, delivering at term. The datasets included measurements from the immunome, transcriptome, microbiome, proteome and metabolome of samples obtained simultaneously from the same patients. Multivariate predictive modeling using the Elastic Net (EN) algorithm was used to measure the ability of each dataset to predict gestational age. Using stacked generalization, these datasets were combined into a single model. This model not only significantly increased predictive power by combining all datasets, but also revealed novel interactions between different biological modalities. Future work includes expansion of the cohort to preterm-enriched populations and in vivo analysis of immune-modulating interventions based on the mechanisms identified. AVAILABILITY AND IMPLEMENTATION: Datasets and scripts for reproduction of results are available through: https://nalab.stanford.edu/multiomics-pregnancy/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. Ghaemi, Mohammad Sajjad DiGiulio, Daniel B Contrepois, Kevin Callahan, Benjamin Ngo, Thuy T M Lee-McMullen, Brittany Lehallier, Benoit Robaczewska, Anna Mcilwain, David Rosenberg-Hasson, Yael Wong, Ronald J Quaintance, Cecele Culos, Anthony Stanley, Natalie Tanada, Athena Tsai, Amy Gaudilliere, Dyani Ganio, Edward Han, Xiaoyuan Ando, Kazuo McNeil, Leslie Tingle, Martha Wise, Paul Maric, Ivana Sirota, Marina Wyss-Coray, Tony Winn, Virginia D Druzin, Maurice L Gibbs, Ronald Darmstadt, Gary L Lewis, David B Partovi Nia, Vahid Agard, Bruno Tibshirani, Robert Nolan, Garry Snyder, Michael P Relman, David A Quake, Stephen R Shaw, Gary M Stevenson, David K Angst, Martin S Gaudilliere, Brice Aghaeepour, Nima eng K01 LM/LM/NLM NIH HHS/ CIHR /CIHR/Canada U19 AI/AI/NIAID NIH HHS/ R01 HL/HL/NHLBI NIH HHS/ K12 HL/HL/NHLBI NIH HHS/ P30 DK/DK/NIDDK NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England Bioinformatics. Jan 1;35(1):95-103. doi: 10./bioinformatics/bty537.I SomaScan 12/19/ Masvekar R, et al. Cerebrospinal fluid biomarkers link toxic astrogliosis and microglial activation to multiple sclerosis severity Mult Scler Relat Disord 28 34-43 https://www.doi.org/10./j.msard..11.032 30,553,167 Adolescent Adult Aged Astrocytes/metabolism Biomarkers/cerebrospinal fluid Cell Culture Techniques Cells, Cultured Cluster Analysis Female Gliosis/*cerebrospinal fluid Humans Male Microglia/metabolism Middle Aged Multiple Sclerosis/*cerebrospinal fluid Prospective Studies Severity of Illness Index Young Adult CNS tissue destruction CSF biomarkers MS severity Microglial activation Multiple sclerosis Toxic astrogliosis BACKGROUND: Once multiple sclerosis (MS) reaches the progressive stage, immunomodulatory treatments have limited efficacy. This suggests that processes other than activation of innate immunity may at least partially underlie disability progression during late stages of MS. Pathology identified these alternative processes as aberrant activation of astrocytes and microglia, and subsequent degeneration of oligodendrocytes and neurons. However, we mostly lack biomarkers that could measure central nervous system (CNS) cell-specific intrathecal processes in living subjects. This prevents differentiating pathogenic processes from an epiphenomenon. Therefore, we sought to develop biomarkers of CNS cell-specific processes and link them to disability progression in MS. METHODS: In a blinded manner, we measured over proteins in the cerebrospinal fluid (CSF) of 431 patients with neuroimmunological diseases and healthy volunteers using modified DNA-aptamers (SOMAscan(R)). We defined CNS cell type-enriched clusters using variable cluster analysis, combined with in vitro modeling. Differences between diagnostic categories were identified in the training cohort (n_=_217) and their correlation to disability measures were assessed; results were validated in an independent validation cohort (n_=_214). RESULTS: Astrocyte cluster 8 (MMP7, SERPINA3, GZMA and CLIC1) and microglial cluster 2 (DSG2 and TNFRSF25) were reproducibly elevated in MS and had a significant and reproducible correlation with MS severity suggesting their pathogenic role. In vitro studies demonstrated that proteins of astrocyte cluster 8 are noticeably released upon stimulation with proinflammatory stimuli and overlap with the phenotype of recently described neuro-toxic (A1) astrocytes. CONCLUSION: Microglial activation and toxic astrogliosis are associated with MS disease process and may partake in CNS tissue destruction. This hypothesis should be tested in new clinical trials. Masvekar, Ruturaj Wu, Tianxia Kosa, Peter Barbour, Christopher Fossati, Valentina Bielekova, Bibiana eng ZIA NS-11/Intramural NIH HHS/ Clinical Trial Netherlands Mult Scler Relat Disord. Feb;28:34-43. doi: 10./j.msard..11.032. Epub Dec 5.I SomaScan 12/16/ Halama A, et al. Metabolic and proteomic signatures of hypoglycaemia in type 2 diabetes Diabetes Obes Metab 21 4 909-919 https://www.doi.org/10./dom. 30,525,282 Adult Amino Acids/metabolism Bile Acids and Salts/metabolism Blood Glucose/metabolism Case-Control Studies Diabetes Mellitus, Type 2/*metabolism Fatty Acids/metabolism Female Glucose Clamp Technique Healthy Volunteers Humans Hypoglycemia/*metabolism Inflammation/metabolism Lipid Metabolism Male *Metabolomics Middle Aged *Proteomics Steroids/metabolism clinical physiology glucose metabolism hypoglycaemia type 2 diabetes AIMS: To determine the biochemical changes that underlie hypoglycaemia in a healthy control group and in people with type 2 diabetes (T2D). MATERIALS AND METHODS: We report a hypoglycaemic clamp study in seven healthy controls and 10 people with T2D. Blood was withdrawn at four time points: at baseline after an overnight fast; after clamping to euglycaemia at 5 mmol/L; after clamping to hypoglycaemia at 2.8 mmol/L; and 24 hours later, after overnight fast. Deep molecular phenotyping using non-targeted metabolomics and the SomaLogic aptamer-based proteomics platform was performed on collected samples. RESULTS: A total of 955 metabolites and proteins were identified, with significant alterations in >90 molecules. A number of metabolites significantly increased during hypoglycaemia, but only cortisol, adenosine-3',5'-cyclic monophosphate (cyclic AMP), and pregnenolone sulphate, were independent of insulin. By contrast, identified protein changes were triggered by hypoglycaemia rather than insulin. The T2D group had significantly higher levels of fatty acids including 10-nonadecenoate, linolenate and dihomo-linoleate during hypoglycaemia compared with the control group. Molecules contributing to cardiovascular complications such as fatty-acid-binding protein-3 and pregnenolone sulphate were altered in the participants with T2D during hypoglycaemia. Almost all molecules returned to baseline at 24 hours. CONCLUSIONS: The present study provides a comprehensive description of molecular events that are triggered by insulin-induced hypoglycaemia. We identified deregulated pathways in T2D that may play a role in the pathophysiology of hypoglycaemia-induced cardiovascular complications. Halama, Anna Kahal, Hassan Bhagwat, Aditya M Zierer, Jonas Sathyapalan, Thozhukat Graumann, Johannes Suhre, Karsten Atkin, Stephen L eng Research Support, Non-U.S. Gov't England Diabetes Obes Metab. Apr;21(4):909-919. doi: 10./dom.. Epub Dec 27.I SomaScan 12/14/ Wu D, et al. Osteitis is associated with dysregulated pro-osteoblastic activity in patients with nasal polyps Laryngoscope 129 3 E102-E109 https://www.doi.org/10./lary. 30,537,181 Adult Bone Morphogenetic Proteins/*metabolism Case-Control Studies Down-Regulation Female Humans Male Middle Aged Nasal Polyps/*metabolism Osteitis/*metabolism Osteoblasts/*metabolism Prospective Studies Rhinitis/*metabolism Signal Transduction Sinusitis/*metabolism Osteitis bone morphogenetic protein pathway chronic rhinosinusitis nasal polyps OBJECTIVES/HYPOTHESIS: The overlying inflammatory mucosa plays a crucial role in the initiation of osteitis; however, the molecular mechanism is unclear. The objective of this study was to explore the bone morphogenetic protein (BMP) pathway and to correlate the expression of key signaling molecules with the degree of osteitis in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). STUDY DESIGN: Prospective experimental analysis. METHODS: This was an institutional review board-approved study in which mucosal samples were obtained from sites of osteitis in CRSwNP and compared to nonosteitic healthy controls (n = 10/group). Protein expression of key BMP pathway was quantified by aptamer-based protein array and confirmed by a set of selected mRNA analyses. Degree of osteitis was assessed using both Kennedy Osteitis Score and Global Osteitis Score (GOS). RESULTS: Pro-osteoblastic expression of BMP7 (fold change [FC] = -1.18, P = .017) and BMP9 (FC = -1.32, P = .023), their receptors, BMP receptor type-1A (BMPR1A) (FC = -2.56, P = .005) and BMP receptor type-2 (FC = -1.28, P = .022), and two enhancers of BMP signaling pathway, the repulsive guidance molecule domain family member B (FC = -1.13, P = .008) and the chordin-like protein 1 (FC = -1.18, P = .027), were all significantly downregulated in CRSwNP. Conversely, the pro-osteoclastic factor, tartrate-resistant acid phosphatase type 5 (ACP5) (FC = 2.36, P = .001), was significantly increased in CRSwNP. GOS was inversely correlated with levels of BMP7 (r = -0.684, P = .005) and BMPR1A (r = -0.864, P = .005) and positively correlated with levels of ACP5 (r = 0.815, P = .004). The FCs among the proteins studied significantly and positively correlated with the FCs of their mRNA expression (r = 0.908, P = .002). CONCLUSIONS: Downregulated pro-osteoblastic mucosal BMP signaling is strongly and significantly associated with increased osteitis in CRSwNP. LEVEL OF EVIDENCE: NA Laryngoscope, 129:E102-E109, . Wu, Dawei Nocera, Angela L Mueller, Sarina K Finn, Kristen Libermann, Towia A Bleier, Benjamin S eng Laryngoscope. Mar;129(3):E102-E109. doi: 10./lary.. Epub Dec 11.I SomaScan 12/12/ Desai VG, et al. Candidate early predictive plasma protein markers of doxorubicin-induced chronic cardiotoxicity in B6C3F(1) mice Toxicol Appl Pharmacol 363 164-173 https://www.doi.org/10./j.taap..11.016 30,517,846 Administration, Intravenous Animals Antibiotics, Antineoplastic/*toxicity Biomarkers/blood Cardiotoxicity/*blood/etiology/prevention & control Dexrazoxane/administration & dosage Doxorubicin/administration & dosage/*toxicity Heart/drug effects Male Mice Myocardium/pathology Protective Agents/administration & dosage Proteome/analysis/drug effects Proteomics Receptor, Notch1/blood Risk Assessment/methods von Willebrand Factor/analysis Biomarkers Cardiotoxicity Dexrazoxane Doxorubicin Mouse Plasma SOMAscan Proteomic Assay Cardiotoxicity is a serious adverse effect of doxorubicin (DOX) treatment in cancer patients. Currently, there is a lack of sensitive biomarkers to predict the risk of DOX-induced cardiotoxicity. Using SOMAmer-based proteomic technology, proteins were profiled to identify potential early biomarkers of cardiotoxicity in plasma from male B6C3F(1) mice given a weekly intravenous dose of 3_mg/kg DOX or saline (SAL) for 2, 3, 4, 6, or 8_weeks (6, 9, 12, 18, or 24_mg/kg cumulative DOX doses, respectively). Also, a group of mice received the cardio-protectant, dexrazoxane (DXZ; 60_mg/kg; intraperitoneal) 30_min before a weekly DOX or SAL dose. Proteomic analysis in plasma collected a week after the last dose showed a significant >/=1.2-fold change in level of 18 proteins in DOX-treated mice compared to SAL-treated counterparts during 8-week exposure. Of these, neurogenic locus notch homolog protein 1 (NOTCH1), von Willebrand factor (vWF), mitochondrial glutamate carrier 2, Wnt inhibitory factor 1, legumain, and mannan-binding lectin serine protease 1 were increased in plasma at 6_mg/kg cumulative DOX dose, prior to the release of myocardial injury marker, cardiac troponin I at 12_mg/kg and higher cumulative doses. These six proteins also remained significantly elevated following myocardial injury or pathology at 24_mg/kg. Pretreatment of mice with DXZ significantly attenuated DOX-induced elevated levels of only NOTCH1 and vWF with mitigation of cardiotoxicity. This suggests NOTCH1 and vWF as candidate early biomarkers of DOX cardiotoxicity, which may help in addressing a clinically important question of identifying cancer patients at risk for cardiotoxicity. Desai, Varsha G Lee, Taewon Moland, Carrie L Vijay, Vikrant Han, Tao Lewis, Sherry M Herman, Eugene H Fuscoe, James C eng Research Support, U.S. Gov't, P.H.S. Toxicol Appl Pharmacol. Jan 15;363:164-173. doi: 10./j.taap..11.016. Epub Dec 2.I SomaScan 12/06/ Mueller SK, et al. Noninvasive exosomal proteomic biosignatures, including cystatin SN, peroxiredoxin-5, and glycoprotein VI, accurately predict chronic rhinosinusitis with nasal polyps Int Forum Allergy Rhinol 9 2 177-186 https://www.doi.org/10./alr. 30,485,711 Adult Chronic Disease Exosomes/*metabolism Female Humans Male Middle Aged Nasal Polyps/*diagnosis Peroxiredoxins/*metabolism Platelet Membrane Glycoproteins/*metabolism Predictive Value of Tests Prognosis Proteome Rhinitis/*diagnosis Salivary Cystatins/*metabolism Sinusitis/*diagnosis Transcriptome Young Adult and platelet glycoprotein VI biosignature chronic rhinosinusitis cystatin-SN exosome mucus nasal polyps peroxiredoxin-5 proteomics BACKGROUND: Exosomes are secreted epithelial-derived vesicles that contain a conserved protein array representative of their parent cell. Exosomes may be reproducibly and noninvasively purified from nasal mucus. The exosomal proteome can be quantified using SOMAscan(TM) , a highly multiplexed, aptamer-based proteomic platform. The purpose of this study was to determine whether chronic rhinosinusitis with nasal polyps (CRSwNP) has a unique predictive exosomal proteomic biosignature. METHODS: Exosomes were isolated from whole mucus sampled from control and CRSwNP patients (n = 20 per group) by differential ultracentrifugation. The SOMAscan(TM) platform was used to simultaneously quantify biologically relevant human proteins. Matched tissue and whole mucus proteomes were also analyzed. Differential protein expression and discriminatory power were calculated using the unweighted pair group method with arithmetic-mean and principal component analysis, respectively. Bioinformatic analysis was performed using Ingenuity Pathway, MetaCore, and GeneMANIA analyses. RESULTS: The exosomal proteome demonstrated 123 significantly (p /= 55 years of age and >/= 30 pack-years, the diagnostic performance was improved, showing 73.3% sensitivity and 90.5% specificity with an area under the curve of 0.88. AptoDetect-Lung (Aptamer Sciences Inc.) offers the best validated performance to discriminate NSCLC from benign nodule controls in a high-risk population and could play a complementary role in lung cancer screening. Jung, Young Ju Oh, In-Jae Kim, Youndong Jung, Jong Ha Seok, Minkyoung Lee, Woochang Park, Cheol Kyu Lim, Jung-Hwan Kim, Young-Chul Kim, Woo-Sung Choi, Chang-Min eng Korea (South) J Korean Med Sci. Dec 13;33(53):e342. doi: 10./jkms..33.e342. eCollection Dec 31.I SomaScan 01/01/ Mosley JD, et al. Probing the Virtual Proteome to Identify Novel Disease Biomarkers Circulation 138 22 - https://www.doi.org/10./CIRCULATIONAHA.118. 30,571,344 Adult Aged Aged, 80 and over Biomarkers/*blood Carotid Artery Diseases/*diagnosis/genetics Female *Genome-Wide Association Study Genotype Humans Lectins, C-Type/analysis Male Middle Aged Odds Ratio Phenotype Polymorphism, Single Nucleotide Proteome/*analysis Proteomics Receptor, Platelet-Derived Growth Factor beta/blood atherosclerosis biomarkers electronic health records BACKGROUND: Proteomic approaches allow measurement of thousands of proteins in a single specimen, which can accelerate biomarker discovery. However, applying these technologies to massive biobanks is not currently feasible because of the practical barriers and costs of implementing such assays at scale. To overcome these challenges, we used a virtual proteomic" approach, linking genetically predicted protein levels to clinical diagnoses in >40 000 individuals. METHODS: We used genome-wide association data from the Framingham Heart Study (n=759) to construct genetic predictors for plasma protein levels. We validated the genetic predictors for 268 proteins and used them to compute predicted protein levels in 41 288 genotyped individuals in the Electronic Medical Records and Genomics (eMERGE) cohort. We tested associations for each predicted protein with clinical phenotypes. Lead associations were validated with directly measured protein levels and either low-density lipoprotein cholesterol or subclinical atherosclerosis in the MDCS (Malmo Diet and Cancer Study; n=651). RESULTS: In the virtual proteomic analysis in eMERGE, 55 proteins were associated with 89 distinct diagnoses at a false discovery rate q proteins. In the present study, we performed SOMAscan analysis of plasma samples and validated the measurements by comparison with selected biomarkers. We compared concentrations of SOMAscan-measured prostate specific antigen (PSA) between males and females, and validated SOMAscan concentrations of fibroblast growth factor 23 (FGF23), FGF receptor 1 (FGFR1), and FGFR4 using Enzyme-Linked immunosorbent assay (ELISA). The median (25th and 75th percentile) SOMAscan PSA level in males and females was .7 (.4 to .5) and 547.8 (521.8 to 993.4) relative fluorescence units (p = 0.002), respectively, suggesting biological plausibility. Pearson correlation between SOMAscan and ELISA was high for FGF23 (R = 0.95, p 8 days. Among the 33 proteins that increased, higher serum levels of fibroblast growth factor-23 (FGF23), tissue plasminogen activator (tPA), neutrophil collagenase (matrix metalloproteinase-8), and soluble urokinase plasminogen activator receptor, when stratified by tertiles, were associated with higher mortality. The association with mortality persisted for each of these proteins after adjusting for other potential risk factors, including age, sex, cardiovascular sequential organ failure assessment score, congestive heart failure, and presence of diabetes. Upper tertile levels of FGF23, tPA, and interleukin-6 on day 8 were associated with increased mortality; however, FGF23 barely lost significance after multivariable adjustment. CONCLUSIONS: Our results underscore an emerging proteomics tool capable of identifying low-abundance serum proteins important not only in the pathogenesis of AKI-D, but which is also helpful in discriminating AKI-D patients with high mortality. Yu, Li-Rong Sun, Jinchun Daniels, Jaclyn R Cao, Zhijun Schnackenberg, Laura Choudhury, Devasmita Palevsky, Paul M Ma, Jennie Z Beger, Richard D Portilla, Didier eng R01 DK/DK/NIDDK NIH HHS/ Y01 DK/DK/NIDDK NIH HHS/ Kidney Int Rep. May 3;3(5):-. doi: 10./j.ekir..04.012. eCollection Sep.I SomaScan 09/11/ Moore RP, et al. Improving probes for super-resolution Nat Methods 15 9 659-660 https://www.doi.org/10./s-018--1 30,171,240 *DNA Microscopy, Fluorescence *Oligonucleotides Moore, Regan P Legant, Wesley R eng Comment Nat Methods. Sep;15(9):659-660. doi: 10./s-018--1.I SomaScan 09/02/ Curran AM, et al. A proteomic signature that reflects pancreatic beta-cell function PLoS One 13 8 e https://www.doi.org/10./journal.pone. 30,161,145 Adult Area Under Curve Body Mass Index Calcineurin/metabolism Cell Line Female Glucose Tolerance Test Humans Insulin Secretion/drug effects Insulin-Secreting Cells/cytology/*metabolism Interleukin-17/genetics/metabolism/pharmacology Linear Models Male Metabolic Networks and Pathways Proteome/*metabolism *Proteomics ROC Curve Young Adult beta-Endorphin/metabolism AIM: Proteomics has the potential to enhance early identification of beta-cell dysfunction, in conjunction with monitoring the various stages of type 2 diabetes onset. The most routine method of assessing pancreatic beta-cell function is an oral glucose tolerance test, however this method is time consuming and carries a participant burden. The objectives of this research were to identify protein signatures and pathways related to pancreatic beta-cell function in fasting blood samples. METHODS: Beta-cell function measures were calculated for MECHE study participants who completed an oral glucose tolerance test and had proteomic data (n = 100). Information on 1,129 protein levels was obtained using the SOMAscan assay. Receiver operating characteristic curves were used to assess discriminatory ability of proteins of interest. Subsequent in vitro experiments were performed using the BRIN-BD11 pancreatic beta-cell line. Replication of findings were achieved in a second human cohort where possible. RESULTS: Twenty-two proteins measured by aptamer technology were significantly associated with beta-cell function/HOMA-IR while 17 proteins were significantly associated with the disposition index (p = 0.01). Receiver operator characteristic curves determined the protein panels to have excellent discrimination between low and high beta-cell function. Linear regression analysis determined that beta-endorphin and IL-17F have strong associations with beta-cell function/HOMA-IR, beta = 0.039 (p = 0.005) and beta = -0.027 (p = 0.013) respectively. Calcineurin and CRTAM were strongly associated with the disposition index (beta = 0.005 and beta = 0.005 respectively, p = 0.012). In vitro experiments confirmed that IL-17F modulated insulin secretion in the BRIN-BD11 cell line, with the lower concentration of 10 ng/mL significantly increasing glucose stimulated insulin secretion (p = 0.043). CONCLUSIONS: Early detection of compromised beta-cell function could allow for implementation of nutritional and lifestyle interventions before progression to type 2 diabetes. Curran, Aoife M Scott-Boyer, Marie Pier Kaput, Jim Ryan, Miriam F Drummond, Elaine Gibney, Eileen R Gibney, Michael J Roche, Helen M Brennan, Lorraine eng Research Support, Non-U.S. Gov't PLoS One. Aug 30;13(8):e. doi: 10./journal.pone.. eCollection .I SomaScan 08/31/ Dudani JS, et al. Classification of prostate cancer using a protease activity nanosensor library Proc Natl Acad Sci U S A 115 36 - https://www.doi.org/10./pnas. 30,126,988 Animals *Biomarkers, Tumor/biosynthesis/genetics *Gene Expression Profiling *Gene Library Heterografts Humans Male Mice Mice, Nude Neoplasm Transplantation *Neoplasms, Experimental/classification/genetics/metabolism *Prostatic Neoplasms/classification/genetics/metabolism activity-based nanosensors diagnostic biomarkers prognostic biomarkers prostate cancer proteolytic enzymes patent application related to this work. A.D.W. is currently an employee of Glympse Bio. S.N.B. is a shareholder of and consultant to Glympse Bio. Improved biomarkers are needed for prostate cancer, as the current gold standards have poor predictive value. Tests for circulating prostate-specific antigen (PSA) levels are susceptible to various noncancer comorbidities in the prostate and do not provide prognostic information, whereas physical biopsies are invasive, must be performed repeatedly, and only sample a fraction of the prostate. Injectable biosensors may provide a new paradigm for prostate cancer biomarkers by querying the status of the prostate via a noninvasive readout. Proteases are an important class of enzymes that play a role in every hallmark of cancer; their activities could be leveraged as biomarkers. We identified a panel of prostate cancer proteases through transcriptomic and proteomic analysis. Using this panel, we developed a nanosensor library that measures protease activity in vitro using fluorescence and in vivo using urinary readouts. In xenograft mouse models, we applied this nanosensor library to classify aggressive prostate cancer and to select predictive substrates. Last, we coformulated a subset of nanosensors with integrin-targeting ligands to increase sensitivity. These targeted nanosensors robustly classified prostate cancer aggressiveness and outperformed PSA. This activity-based nanosensor library could be useful throughout clinical management of prostate cancer, with both diagnostic and prognostic utility. Dudani, Jaideep S Ibrahim, Maria Kirkpatrick, Jesse Warren, Andrew D Bhatia, Sangeeta N eng P30 CA/CA/NCI NIH HHS/ P30 ES/ES/NIEHS NIH HHS/ HHMI/Howard Hughes Medical Institute/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Proc Natl Acad Sci U S A. Sep 4;115(36):-. doi: 10./pnas.. Epub Aug 20.I SomaScan 08/22/ Strauss S, et al. Modified aptamers enable quantitative sub-10-nm cellular DNA-PAINT imaging Nat Methods 15 9 685-688 https://www.doi.org/10./s-018--0 30,127,504 Aptamers, Nucleotide/*chemistry Green Fluorescent Proteins/chemistry Limit of Detection Microscopy, Fluorescence/methods Although current implementations of super-resolution microscopy are technically approaching true molecular-scale resolution, this has not translated to imaging of biological specimens, because of the large size of conventional affinity reagents. Here we introduce slow off-rate modified aptamers (SOMAmers) as small and specific labeling reagents for use with DNA points accumulation in nanoscale topography (DNA-PAINT). To demonstrate the achievable resolution, specificity, and multiplexing capability of SOMAmers, we labeled and imaged both transmembrane and intracellular targets in fixed and live cells. Strauss, Sebastian Nickels, Philipp C Strauss, Maximilian T Jimenez Sabinina, Vilma Ellenberg, Jan Carter, Jeffrey D Gupta, Shashi Janjic, Nebojsa Jungmann, Ralf eng /ERC_/European Research Council/International Research Support, Non-U.S. Gov't Nat Methods. Sep;15(9):685-688. doi: 10./s-018--0. Epub Aug 20.I SomaScan 08/22/ Rice LM, et al. Serum biomarker for diagnostic evaluation of pulmonary arterial hypertension in systemic sclerosis Arthritis Res Ther 20 1 185 https://www.doi.org/10./s-018--8 30,115,106 Aged Aged, 80 and over Biomarkers/*blood Early Diagnosis Female Follistatin-Related Proteins/*blood Humans Hypertension, Pulmonary/blood/*diagnosis/*etiology Male Middle Aged Midkine/*blood Scleroderma, Systemic/blood/*complications Sensitivity and Specificity Biomarkers Classification Proteomic Pulmonary arterial hypertension Scleroderma tissue and serum samples were enrolled with signed informed written consent by the institutional review board of Boston University. CONSENT FOR PUBLICATION: The manuscript does not contain any individual person's data in any form. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. BACKGROUND: Systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) is one of the leading causes of death in SSc. Identification of a serum-based proteomic diagnostic biomarker for SSc-PAH would allow for rapid non-invasive screening and could positively impact patient survival. Identification and validation of novel proteins could potentially facilitate the identification of SSc-PAH, and might also point to important protein mediators in pathogenesis. METHODS: Thirteen treatment-naive SSc-PAH patients had serum collected at time of diagnosis and were used as the discovery cohort for the protein-expression biomarker. Two proteins, Midkine and Follistatin-like 3 (FSTL3) were then validated by enzyme-linked immunosorbent assays. Midkine and FSTL3 were tested in combination to identify SSc-PAH and were validated in two independent cohorts of SSc-PAH (n = 23, n = 11). RESULTS: Eighty-two proteins were found to be differentially regulated in SSc-PAH sera. Two proteins (Midkine and FSTL3) were also shown to be elevated in publicly available data and their expression was evaluated in independent cohorts. In the validation cohorts, the combination of Midkine and FSTL3 had an area under the receiver operating characteristic curve (AUC) of 0.85 and 0.92 with respective corresponding measures of sensitivity of 76% and 91%, and specificity measures of 76% and 80%. CONCLUSIONS: These findings indicate that there is a clear delineation between overall protein expression in sera from SSc patients and those with SSc-PAH. The combination of Midkine and FSTL3 can serve as an SSc-PAH biomarker and are potential drug targets for this rare disease population. Rice, Lisa M Mantero, Julio C Stratton, Eric A Warburton, Rod Roberts, Kari Hill, Nicholas Simms, Robert W Domsic, Robyn Farber, Harrison W Layfatis, Robert eng R01 AR/AR/NIAMS NIH HHS/ P50 AR/AR/NIAMS NIH HHS/ P30 AR/AR/NIAMS NIH HHS/ Research Support, N.I.H., Extramural England Arthritis Res Ther. Aug 16;20(1):185. doi: 10./s-018--8.I SomaScan 08/18/ Yao C, et al. Genome-wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease Nat Commun 9 1 https://www.doi.org/10./s-018--x 30,111,768 Adult Blood Proteins/*genetics Cardiovascular Diseases/*genetics/metabolism Chromosome Mapping Female Gene Expression Profiling Genetic Predisposition to Disease/*genetics *Genome-Wide Association Study Humans Male Middle Aged Polymorphism, Single Nucleotide Quantitative Trait Loci/*genetics Risk Factors Signal Transduction/genetics Identifying genetic variants associated with circulating protein concentrations (protein quantitative trait loci; pQTLs) and integrating them with variants from genome-wide association studies (GWAS) may illuminate the proteome's causal role in disease and bridge a knowledge gap regarding SNP-disease associations. We provide the results of GWAS of 71 high-value cardiovascular disease proteins in Framingham Heart Study participants and independent external replication. We report the mapping of over 16,000 pQTL variants and their functional relevance. We provide an integrated plasma protein-QTL database. Thirteen proteins harbor pQTL variants that match coronary disease-risk variants from GWAS or test causal for coronary disease by Mendelian randomization. Eight of these proteins predict new-onset cardiovascular disease events in Framingham participants. We demonstrate that identifying pQTLs, integrating them with GWAS results, employing Mendelian randomization, and prospectively testing protein-trait associations holds potential for elucidating causal genes, proteins, and pathways for cardiovascular disease and may identify targets for its prevention and treatment. Yao, Chen Chen, George Song, Ci Keefe, Joshua Mendelson, Michael Huan, Tianxiao Sun, Benjamin B Laser, Annika Maranville, Joseph C Wu, Hongsheng Ho, Jennifer E Courchesne, Paul Lyass, Asya Larson, Martin G Gieger, Christian Graumann, Johannes Johnson, Andrew D Danesh, John Runz, Heiko Hwang, Shih-Jen Liu, Chunyu Butterworth, Adam S Suhre, Karsten Levy, Daniel eng G/MRC_/Medical Research Council/United Kingdom RG/13/13//BHF_/British Heart Foundation/United Kingdom MR/L/1/MRC_/Medical Research Council/United Kingdom /ERC_/European Research Council/International K99 HL/HL/NHLBI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England Nat Commun. Aug 15;9(1):. doi: 10./s-018--x.I SomaScan 08/17/ Norman KC, et al. Proteomics: Clinical and research applications in respiratory diseases Respirology 23 11 993- https://www.doi.org/10./resp. 30,105,802 *Biomedical Research/methods/trends Epigenesis, Genetic Humans Inventions Protein Processing, Post-Translational *Proteomics/methods/trends *Respiratory Tract Diseases/genetics/metabolism/physiopathology application clinical lung disease proteomics research The proteome is the study of the protein content of a definable component of an organism in biology. However, the tissue-specific expression of proteins and the varied post-translational modifications, splice variants and protein-protein complexes that may form, make the study of protein a challenging yet vital tool in answering many of the unanswered questions in medicine and biology to date. Indeed, the spatial, temporal and functional composition of proteins in the human body has proven difficult to elucidate for many years. Given the effect of microRNA and epigenetic regulation on silencing and enhancing gene transcription, the study of protein arguably provides more accurate information on homeostasis and perturbation in health and disease. There have been significant advances in the field of proteomics in recent years, with new technologies and platforms available to the research community. In this review, we briefly discuss some of these new technologies and developments in the context of respiratory disease. We also discuss the types of data science approaches to analyses and interpretation of the large volumes of data generated in proteomic studies. We discuss the application of these technologies with regard to respiratory disease and highlight the potential for proteomics in generating major advances in the understanding of respiratory pathophysiology into the future. Norman, Katy C Moore, Bethany B Arnold, Kelly B O'Dwyer, David N eng K99 HL/HL/NHLBI NIH HHS/ HL/GF/NIH HHS/ AI/GF/NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review Australia Respirology. Nov;23(11):993-. doi: 10./resp.. Epub Aug 13.I SomaScan 08/15/ Mueller SK, et al. Highly multiplexed proteomic analysis reveals significant tissue and exosomal coagulation pathway derangement in chronic rhinosinusitis with nasal polyps Int Forum Allergy Rhinol 8 12 - https://www.doi.org/10./alr. 30,091,854 Adult Blood Coagulation Blood Coagulation Disorders/*metabolism Chronic Disease Exosomes/*metabolism Female Fibrinogen/metabolism Fibronectins/metabolism Humans Male Middle Aged Mucus Nasal Polyps/*metabolism Proteomics Rhinitis/diagnosis/*metabolism Sinusitis/diagnosis/*metabolism Up-Regulation von Willebrand Factor/metabolism biomarker chronic rhinosinusitis microarray nasal polyps sinusitis BACKGROUND: The coagulation pathway has been previously implicated in the etiopathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) through analysis of individual proteins within the cascade. The purpose of this study was to: (1) apply a large-scale proteomic approach to confirm these previous findings; and (2) correlate the protein aberrations between tissue and exosomes to establish exosomal proteomics as a method to probe the pathophysiology of CRSwNP. METHODS: This investigation was an internal review board-approved study in which matched tissue and mucus exosomal proteomes were compared between control and CRSwNP (n = 10/group) using an aptamer-based proteomic array and confirmed using whole transcriptome sequencing. Protein expression and the correlation between samples were calculated using Student's t-test and Benjamini-Hochberg procedures followed by the application of Ingenuity Pathway and MetaCore bioinformatics analyses. RESULTS: Among all protein pathways, the coagulation cascade was the most significantly associated with CRSwNP (p = 2.85e-8). Among the 13 significantly altered coagulation-related tissue proteins, fibronectin and fibrinogen gamma chains were the most overexpressed in CRSwNP relative to control (fold change [FC], 2.59; p = 0.006; and FC, 2.38; p 2-fold change (p /= 0.4) for 91% of proteins. These results demonstrate the feasibility of SOMAscan for analyses of archived plasma samples. Kim, Claire H Tworoger, Shelley S Stampfer, Meir J Dillon, Simon T Gu, Xuesong Sawyer, Sherilyn J Chan, Andrew T Libermann, Towia A Eliassen, A Heather eng UM1 CA/CA/NCI NIH HHS/ R01 CA/CA/NCI NIH HHS/ P30 CA/CA/NCI NIH HHS/ T32 CA/CA/NCI NIH HHS/ R01 CA/CA/NCI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England Sci Rep. May 30;8(1):. doi: 10./s-018--w.I SomaScan 06/01/ Ciampa E, et al. Cerebrospinal Fluid Protein Changes in Preeclampsia Hypertension 72 1 219-226 https://www.doi.org/10./HYPERTENSIONAHA.118. 29,844,151 Adult Biomarkers/cerebrospinal fluid Cerebrospinal Fluid Proteins/*cerebrospinal fluid Enzyme-Linked Immunosorbent Assay Female Humans Pre-Eclampsia/*cerebrospinal fluid Pregnancy Prognosis Proteomics/*methods activin brain cerebrospinal fluid proteins hypertension preeclampsia proteomics The molecular mechanisms underlying seizure susceptibility in preeclampsia are unknown. We hypothesized that altered expression of distinct proteins in the cerebrospinal fluid (CSF) may reflect pathophysiological changes in the central nervous system that contribute to the neurological manifestations of severe preeclampsia. We obtained CSF samples from 13 patients with preeclampsia and 14 control patients during spinal anesthesia before delivery and analyzed them by SOMAscan, an aptamer-based proteomics platform for alterations in protein levels. Ingenuity Pathway Analysis was conducted to highlight relationships between preeclampsia-specific proteins found to be significantly altered. For 2 of the target proteins, we validated the difference in CSF concentrations by ELISA. SOMAscan revealed 82 proteins, whose expression levels were significantly different (P2-fold) in nonsmoking patients with severe asthma compared with MMAs, including IL-1 receptor (IL-1R) family and nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NRLP3) inflammasome members (false discovery rate 400 cells/mul). Participants received open-label aprepitant 375 mg per day for 28 days and were followed for an additional 30 days. Changes in plasma levels of proinflammatory markers were assessed using flow cytometry, ELISA, luminex, and SOMAscan assays. RESULTS: The mean peak aprepitant plasma concentration was 30.7 +/- 15.3 mug/ml at day 14 and 23.3 +/- 12.3 mug/ml at day 28. Aprepitant treatment resulted in decreased plasma SP levels and affected 176 plasma proteins (56 after FDR) and several metabolic pathways, including inflammation and lipid metabolism. No change in soluble CD163 was observed. Aprepitant treatment was associated with a moderate increases in total and HDL cholesterol and affected select hematologic and metabolic markers, which returned to baseline levels 30 days after aprepitant treatment was stopped. There were 12 mild and 10 moderate adverse events (AE). CONCLUSIONS: Aprepitant is safe and well tolerated. The antiinflammatory properties of aprepitant make it a possible adjunctive therapy for comorbid conditions associated with HIV infection. TRIAL REGISTRATION: ClinicalTrials.gov (NCT). FUNDING: This research was funded by NIH UO1 MH, P30 MH, and PO1 MH. Spitsin, Sergei Tebas, Pablo Barrett, Jeffrey S Pappa, Vasiliki Kim, Deborah Taylor, Deanne Evans, Dwight L Douglas, Steven D eng P01 MH/MH/NIMH NIH HHS/ P30 MH/MH/NIMH NIH HHS/ U01 MH/MH/NIMH NIH HHS/ UM1 AI/AI/NIAID NIH HHS/ Clinical Trial, Phase I Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't JCI Insight. Oct 5;2(19):e. doi: 10./jci.insight..I SomaScan 10/06/ Gupta S, et al. Pharmacokinetic Properties of DNA Aptamers with Base Modifications Nucleic Acid Ther 27 6 345-353 https://www.doi.org/10./nat.. 28,961,063 Animals Aptamers, Nucleotide/administration & dosage/blood/*chemistry/*pharmacokinetics Base Sequence Drug Design Hydrophobic and Hydrophilic Interactions Ligands Linear Models Male Polyethylene Glycols/*chemistry/metabolism Rats Rats, Sprague-Dawley SELEX Aptamer Technique/methods Statistics, Nonparametric Uracil/*chemistry/metabolism aptamer pharmacokinetics modified nucleotides plasma clearance side chains N.J. are employees and stakeholders of SomaLogic, Inc. T.S., M.H., and Y.I. are employees and stakeholders of Otsuka Pharmaceutical Co., Ltd. The addition of novel side chains at the 5-position of uracil is an effective means to increase chemical diversity of aptamers and hence the success rate for discovery of high-affinity ligands to protein targets. Such modifications also increase nuclease resistance, which is useful in a range of applications, especially for therapeutics. In this study, we assess the impact of these side chains on plasma pharmacokinetics of modified aptamers conjugated to a 40 kDa polyethylene glycol. We show that clearance from plasma depends on relative hydrophobicity: side chains with a negative cLogP (more hydrophilic) result in slower plasma clearance compared with side chains with a positive cLogP (more hydrophobic). We show that clearance increases with the number of side chains in sequences of >/=28 synthons, but this effect is dramatically diminished in shorter sequences. These results serve as a guide for the design of new therapeutic aptamers with diversity-enhancing side chains. Gupta, Shashi Drolet, Daniel W Wolk, Steven K Waugh, Sheela M Rohloff, John C Carter, Jeffery D Mayfield, Wesley S Otis, Matthew R Fowler, Catherine R Suzuki, Tomoki Hirota, Masao Ishikawa, Yuichi Schneider, Daniel J Janjic, Nebojsa eng Nucleic Acid Ther. Dec;27(6):345-353. doi: 10./nat... Epub Sep 29.I SomaScan 09/30/ Welton JL, et al. Cerebrospinal fluid extracellular vesicle enrichment for protein biomarker discovery in neurological disease; multiple sclerosis J Extracell Vesicles 6 1 https://www.doi.org/10./.. 28,959,386 Extracellular vesicles biomarkers cerebrospinal fluid multiple sclerosis proteomics size exclusion chromatography The discovery of disease biomarkers, along with the use of liquid biopsies" as a minimally invasive source of biomarkers, continues to be of great interest. In inflammatory diseases of the central nervous system (CNS), cerebrospinal fluid (CSF) is the most obvious biofluid source. Extracellular vesicles (EVs) are also present in CSF and are thought to be potential "biomarker treasure chests". However, isolating these CSF-derived EVs remains challenging. This small-scale pilot study developed and tested a protocol to enrich for CSF-EVs, both in relapsing remitting multiple sclerosis (RRMS) CSF and controls. These were subsequently compared, using an aptamer based proteomics array, SOMAscan. EVs were enriched from RRMS patient (n = 4) and non-demyelinating control (idiopathic intracranial hypertension (IIH) (n = 3)) CSF using precipitation and mini size-exclusion chromatography (SEC). EV-enriched fractions were selected using pre-defined EV characteristics, including increased levels of tetraspanins. EVs and paired CSF were analysed by SOMAscan, providing relative abundance data for proteins. CSF-EVs were characterised, revealing exosome-like features: rich in tetraspanins CD9 and CD81, size ~100 nm, and exosome-like morphology by TEM. Sufficient quantities of, SOMAscan compatible, EV material was obtained from 5 ml CSF for proteomics analysis. Overall, 348 and 580 proteins were identified in CSF-EVs and CSF, respectively, of which 50 were found to be significantly (t-test) and exclusively enriched in RRMS CSF-EVs. Selected proteins, Plasma kallikrein and Apolipoprotein-E4, were further validated by western blot and appeared increased in CSF-EVs compared to CSF. Functional enrichment analysis of the 50 enriched proteins revealed strong associations with biological processes relating to MS pathology and also extracellular regions, consistent with EV enrichment. This pilot study demonstrates practicality for EV enrichment in CSF derived from patients with MS and controls, allowing detailed analysis of protein profiles that may offer opportunities to identify novel biomarkers and therapeutic approaches in CNS inflammatory diseases." Welton, Joanne L Loveless, Samantha Stone, Timothy von Ruhland, Chris Robertson, Neil P Clayton, Aled eng MR/L/1/MRC_/Medical Research Council/United Kingdom J Extracell Vesicles. Sep 3;6(1):. doi: 10./... eCollection .I SomaScan 09/30/ Curran AM, et al. Sexual Dimorphism, Age, and Fat Mass Are Key Phenotypic Drivers of Proteomic Signatures J Proteome Res 16 11 - https://www.doi.org/10./acs.jproteome.7b 28,950,061 Adipose Tissue Age Factors Female Humans Male *Phenotype Proteomics/*methods Sex Characteristics age biomarker fat mass pathway phenotype protein proteomics sex Validated protein biomarkers are needed for assessing health trajectories, predicting and subclassifying disease, and optimizing diagnostic and therapeutic clinical decision-making. The sensitivity, specificity, accuracy, and precision of single or combinations of protein biomarkers may be altered by differences in physiological states limiting the ability to translate research results to clinically useful diagnostic tests. Aptamer based affinity assays were used to test whether low abundant serum proteins differed based on age, sex, and fat mass in a healthy population of 94 males and 102 females from the MECHE cohort. The findings were replicated in 217 healthy male and 377 healthy female participants in the DiOGenes consortium. Of the proteins in the panel, 141, 51, and 112 proteins (adjusted p /= 28%) compared to normal healthy volunteer subjects. The DMD with cardiomyopathy group had significantly lower average EF and SF (EF = 45 +/- 10/SF = 25 +/- 2%) than the DMD without cardiomyopathy group (EF = 58 +/- 5% and SF = 32 +/- 3%; p /=34 weeks of gestation). Maternal plasma samples were collected throughout gestation (normal pregnancy: 2-6 samples per patient, median of 2; late-onset preeclampsia: 2-6, median of 5). The abundance of 1,125 proteins was measured using an aptamers-based proteomics technique. Protein abundance in normal pregnancies was modeled using linear mixed-effects models to estimate mean abundance as a function of gestational age. Data was then expressed as multiples of-the-mean (MoM) values in normal pregnancies. Multi-marker prediction models were built using data from one of five gestational age intervals (8-16, 16.1-22, 22.1-28, 28.1-32, 32.1-36 weeks of gestation). The predictive performance of the best combination of proteins was compared to placental growth factor (PIGF) using bootstrap. RESULTS: 1) At 8-16 weeks of gestation, the best prediction model included only one protein, matrix metalloproteinase 7 (MMP-7), that had a sensitivity of 69% at a false positive rate (FPR) of 20% (AUC = 0.76); 2) at 16.1-22 weeks of gestation, MMP-7 was the single best predictor of late-onset preeclampsia with a sensitivity of 70% at a FPR of 20% (AUC = 0.82); 3) after 22 weeks of gestation, PlGF was the best predictor of late-onset preeclampsia, identifying 1/3 to 1/2 of the patients destined to develop this syndrome (FPR = 20%); 4) 36 proteins were associated with late-onset preeclampsia in at least one interval of gestation (after adjustment for covariates); 5) several biological processes, such as positive regulation of vascular endothelial growth factor receptor signaling pathway, were perturbed; and 6) from 22.1 weeks of gestation onward, the set of proteins most predictive of severe preeclampsia was different from the set most predictive of the mild form of this syndrome. CONCLUSIONS: Elevated MMP-7 early in gestation (8-22 weeks) and low PlGF later in gestation (after 22 weeks) are the strongest predictors for the subsequent development of late-onset preeclampsia, suggesting that the optimal identification of patients at risk may involve a two-step diagnostic process. Erez, Offer Romero, Roberto Maymon, Eli Chaemsaithong, Piya Done, Bogdan Pacora, Percy Panaitescu, Bogdan Chaiworapongsa, Tinnakorn Hassan, Sonia S Tarca, Adi L eng HHSNC/HD/NICHD NIH HHS/ PLoS One. Jul 24;12(7):e. doi: 10./journal.pone.. eCollection .I SomaScan 07/25/ Sun HH, et al. Diagnosis and prognosis-review of biomarkers for mesothelioma Ann Transl Med 5 11 244 https://www.doi.org/10./atm..06.60 28,706,912 Mesothelioma asbestos biomarker diagnosis prognosis Malignant pleural mesothelioma (MPM) is an aggressive disease arising in pleural cell lining and is associated with asbestos exposure. Today, there is a rising incidence of MPM reaching 3,000 annual cases nationally, primarily from the large population occupationally exposed to asbestos between and . With a prolonged latency period, presenting clinically 10 to 40 years after exposure, MPM is often diagnosed in late stages and presents median survival time of less than 12 months. There is a serious need for improvement in prognostic and diagnostic tools for MPM. Recent investigation and discovery of various biomarkers has shown promise, including Osteopontin, Fibulin-3, Soluble Mesothelin-Related Proteins (SMRP), High Mobility Group Box 1 (HMGB1), micro-RNA's, peripheral blood-based markers, and Slow Off-rate Modified Aptamer (SOMAmer) proteomic assays. In this review, we explore these current major biomarkers and their prognostic and diagnostic potential, highlighting the most recent large studies and developments for each. While progress has been made in mesothelioma research, many questions remain unanswered. Increased international cooperation is necessary for improving validity of results for current biomarkers through repeated investigation and increasing cohort sizes, as well as for the continued search for new and better markers. Sun, Huan H Vaynblat, Allen Pass, Harvey I eng Review China Ann Transl Med. Jun;5(11):244. doi: 10./atm..06.60.I SomaScan 07/15/ Wang J, et al. Identification of unique proteomic signatures in allergic and non-allergic skin disease Clin Exp Allergy 47 11 - https://www.doi.org/10./cea. 28,703,865 Case-Control Studies Cluster Analysis Dermatitis, Atopic/*immunology/*metabolism Dermatitis, Contact/immunology/metabolism Female Humans Immunoglobulin E/blood/immunology Inflammation Mediators/blood/metabolism Male *Proteome *Proteomics/methods Skin Diseases/etiology/*metabolism atopic dermatitis biomarkers clinical immunology contact dermatitis dermatology psoriasis BACKGROUND: Atopic dermatitis (AD), psoriasis (PS), and contact dermatitis (CD) are common skin diseases, characterized by barrier disruption and systemic inflammation, with unique epidermal signatures and common inflammatory pathways identified by transcriptomic profiling. This study profiled proteomic signatures in serum from subjects with AD, PS, and CD compared with healthy controls (HC). OBJECTIVE: Identify unique proteomic signatures to distinguish between inflammatory diseases with similar epidermal disruption and overlapping epithelial inflammation. METHODS: Sera from 20 subjects with moderate to severe AD, 10 subjects with CD, 12 subjects with moderate to severe PS, 10 subjects with both AD and CD, and 10 HC with no history of skin disease was analysed using high-throughput proteomic analysis that detects expression of protein targets. Protein expression was compared between disease and HC, and across diseases for statistical significance (fold change>/=1.5 and false discovery rate=0.05), to identify unique proteomic signatures for each disease. RESULTS: Complement C5A anaphylatoxin (C5A), lipopolysaccharide binding protein (LBP), C-reactive protein (CRP), ILT-4, C-C motif ligand 18 (PARC), and sialic acid-binding Ig-like lectin 14 (SIG14) were significantly modulated in all three diseases compared with HC. We identified unique signatures for AD (Immunoglobulin E (IgE), thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC)), CD (10 proteins), and PS (kynureninase (KYNU)). Proteomic profiling in subjects with both AD and CD identified additional dysregulated proteins compared with subjects with either condition alone, indicating an exacerbated inflammation reaction. CONCLUSIONS AND CLINICAL RELEVANCE: Unique sera proteomic signatures may distinguish between inflammatory skin diseases despite similar epidermal barrier disruption and epithelial inflammation. This may provide insight into disease pathogenesis, diagnosis, and therapeutic intervention in difficult-to-treat subjects. Wang, J Suarez-Farinas, M Estrada, Y Parker, M L Greenlees, L Stephens, G Krueger, J Guttman-Yassky, E Howell, M D eng England Clin Exp Allergy. Nov;47(11):-. doi: 10./cea.. Epub Aug 11.I SomaScan 07/14/ Giannitsis E, et al. Aptamer-based proteomic profiling for prognostication in pulmonary arterial hypertension Lancet Respir Med 5 9 671-672 https://www.doi.org/10./S-(17)-6 28,624,387 Familial Primary Pulmonary Hypertension Gene Expression Profiling Humans *Hypertension, Pulmonary *Proteomics Giannitsis, Evangelos Mueller-Hennessen, Matthias Katus, Hugo A eng Comment England Lancet Respir Med. Sep;5(9):671-672. doi: 10./S-(17)-6. Epub Jun 15.I SomaScan 06/19/ Rhodes CJ, et al. Plasma proteome analysis in patients with pulmonary arterial hypertension: an observational cohort study Lancet Respir Med 5 9 717-726 https://www.doi.org/10./S-(17)-3 28,624,389 Adult Aged Arterial Pressure Biomarkers/blood Blood Proteins/*analysis Cohort Studies Familial Primary Pulmonary Hypertension/*blood/mortality Female Humans Hypertension/*blood/mortality Male Middle Aged Proteome/*analysis Risk Assessment Risk Factors BACKGROUND: Idiopathic and heritable pulmonary arterial hypertension form a rare but molecularly heterogeneous disease group. We aimed to measure and validate differences in plasma concentrations of proteins that are associated with survival in patients with idiopathic or heritable pulmonary arterial hypertension to improve risk stratification. METHODS: In this observational cohort study, we enrolled patients with idiopathic or heritable pulmonary arterial hypertension from London (UK; cohorts 1 and 2), Giessen (Germany; cohort 3), and Paris (France; cohort 4). Blood samples were collected at routine clinical appointment visits, clinical data were collected within 30 days of blood sampling, and biochemical data were collected within 7 days of blood sampling. We used an aptamer-based assay of plasma proteins, and patient clinical details were concealed to the technicians. We identified a panel of prognostic proteins, confirmed with alternative targeted assays, which we evaluated against the established prognostic risk equation for pulmonary arterial hypertension derived from the REVEAL registry. All-cause mortality was the primary endpoint. FINDINGS: 20 proteins differentiated survivors and non-survivors in 143 consecutive patients with idiopathic or heritable pulmonary arterial hypertension with 2 years' follow-up (cohort 1) and in a further 75 patients with 2.5 years' follow-up (cohort 2). Nine proteins were both prognostic independent of plasma NT-proBNP concentrations and confirmed by targeted assays. The functions of these proteins relate to myocardial stress, inflammation, pulmonary vascular cellular dysfunction and structural dysregulation, iron status, and coagulation. A cutoff-based score using the panel of nine proteins provided prognostic information independent of the REVEAL equation, improving the C statistic from area under the curve 0.83 (for REVEAL risk score, 95% CI 0.77-0.89; p0.40. RESULTS: There were 26 children included: mean age 11.3 years (SD 2.4 years), mean Brody Bronchiectasis score 0.65 (SD 0.83), mean airway count 14.3 (SD 5.7) per CT slice. Brody bronchiectasis change over 1 year ranged from -1.0 to 1.9 and airway count change over one year ranged from -7.7 to 13.5 airways per slice. Proteins related to inflammation and extracellular matrix degradation were associated with cross-sectional and longitudinal structural changes. CONCLUSIONS AND CLINICAL RELEVANCE: Imaging outcomes were more strongly correlated with circulating proteins than age or spirometry values. The unique SOMAscan proteomic platform identifies several novel proteins in blood that are associated with bronchiectasis and that may serve as clinically useful biomarkers in children with CF. DeBoer, Emily M Kroehl, Miranda E Wagner, Brandie D Accurso, Frank J Harris, J Kirk Lynch, David A Sagel, Scott D Deterding, Robin R eng KL2 TR/TR/NCATS NIH HHS/ Research Support, N.I.H., Extramural Germany Proteomics Clin Appl. Sep;11(9-10). doi: 10./prca.. Epub May 29.I SomaScan 04/30/ Westwood S, et al. The influence of insulin resistance on cerebrospinal fluid and plasma biomarkers of Alzheimer's pathology Alzheimers Res Ther 9 1 31 https://www.doi.org/10./s-017--6 28,441,961 Alzheimer Disease/*blood/*cerebrospinal fluid Amyloid beta-Peptides/*blood/*cerebrospinal fluid Animals Apolipoprotein E4/*blood/*cerebrospinal fluid Biomarkers/blood/cerebrospinal fluid Humans *Insulin Resistance Male Middle Aged Reproducibility of Results Sensitivity and Specificity Alzheimer's disease Cerebrospinal fluid biomarkers Diabetes mellitus Insulin resistance Plasma biomarkers Proteomics BACKGROUND: Insulin resistance (IR) has previously been associated with an increased risk of developing Alzheimer's disease (AD), although the relationship between IR and AD is not yet clear. Here, we examined the influence of IR on AD using plasma and cerebrospinal fluid (CSF) biomarkers related to IR and AD in cognitively healthy men. We also aimed to characterise the shared protein signatures between IR and AD. METHODS: Fifty-eight cognitively healthy men, 28 IR and 30 non-IR (age and APOE epsilon4 matched), were drawn from the Metabolic Syndrome in Men study in Kuopio, Finland. CSF AD biomarkers (amyloid beta-peptide (Abeta), total tau and tau phosphorylated at the Thr181 epitope) were examined with respect to IR. Targeted proteomics using ELISA and Luminex xMAP assays were performed to assess the influence of IR on previously identified CSF and plasma protein biomarker candidates of AD pathology. Furthermore, CSF and plasma SOMAscan was performed to discover proteins that associate with IR and CSF AD biomarkers. RESULTS: CSF AD biomarkers did not differ between IR and non-IR groups, although plasma insulin correlated with CSF Abeta/tau across the whole cohort. In total, 200 CSF and 487 plasma proteins were differentially expressed between IR and non-IR subjects, and significantly enriched pathways, many of which have been previously implicated in AD, were identified. CSF and plasma proteins significantly associated with CSF AD biomarkers were also discovered, and those sensitive to both IR and AD were identified. CONCLUSIONS: These data indicate that IR is not directly related to the level of CSF AD pathology in cognitively healthy men. Proteins that associated with both AD and IR are potential markers indicative of shared pathology. Westwood, Sarah Liu, Benjamine Baird, Alison L Anand, Sneha Nevado-Holgado, Alejo J Newby, Danielle Pikkarainen, Maria Hallikainen, Merja Kuusisto, Johanna Streffer, Johannes R Novak, Gerald Blennow, Kaj Andreasson, Ulf Zetterberg, Henrik Smith, Ulf Laakso, Markku Soininen, Hilkka Lovestone, Simon eng G/MRC_/Medical Research Council/United Kingdom Review England Alzheimers Res Ther. Apr 26;9(1):31. doi: 10./s-017--6.I SomaScan 04/27/ O'Dwyer DN, et al. The peripheral blood proteome signature of idiopathic pulmonary fibrosis is distinct from normal and is associated with novel immunological processes Sci Rep 7 https://www.doi.org/10./srep 28,440,314 Adult Aged Aged, 80 and over *Blood Proteins/immunology/metabolism Female Humans *Idiopathic Pulmonary Fibrosis/blood/immunology Male Middle Aged *Proteome/immunology/metabolism Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial pneumonia. The disease pathophysiology is poorly understood and the etiology remains unclear. Recent advances have generated new therapies and improved knowledge of the natural history of IPF. These gains have been brokered by advances in technology and improved insight into the role of various genes in mediating disease, but gene expression and protein levels do not always correlate. Thus, in this paper we apply a novel large scale high throughput aptamer approach to identify more than proteins in the peripheral blood of well-characterized IPF patients and normal volunteers. We use systems biology approaches to identify a unique IPF proteome signature and give insight into biological processes driving IPF. We found IPF plasma to be altered and enriched for proteins involved in defense response, wound healing and protein phosphorylation when compared to normal human plasma. Analysis also revealed a minimal protein signature that differentiated IPF patients from normal controls, which may allow for accurate diagnosis of IPF based on easily-accessible peripheral blood. This report introduces large scale unbiased protein discovery analysis to IPF and describes distinct biological processes that further inform disease biology. O'Dwyer, David N Norman, Katy C Xia, Meng Huang, Yong Gurczynski, Stephen J Ashley, Shanna L White, Eric S Flaherty, Kevin R Martinez, Fernando J Murray, Susan Noth, Imre Arnold, Kelly B Moore, Bethany B eng UL1 TR/TR/NCATS NIH HHS/ K24 HL/HL/NHLBI NIH HHS/ R01 HL/HL/NHLBI NIH HHS/ R01 HL/HL/NHLBI NIH HHS/ R01 HL/HL/NHLBI NIH HHS/ T32 AI/AI/NIAID NIH HHS/ Clinical Trial Multicenter Study Observational Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England Sci Rep. Apr 25;7:. doi: 10./srep.I SomaScan 04/26/ Saleheen D, et al. Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity Nature 544 7,649 235-239 https://www.doi.org/10./nature 28,406,212 1-Alkyl-2-acetylglycerophosphocholine Esterase/deficiency/genetics Apolipoprotein C-III/deficiency/genetics Cohort Studies *Consanguinity Coronary Disease/blood/genetics Cytochrome P450 Family 2/genetics *DNA Mutational Analysis Dietary Fats/pharmacology Exome/genetics Fasting/blood Female *Gene Deletion Gene Frequency Genes/*genetics Genetic Association Studies/*methods *Homozygote Humans Interleukin-8/blood Male Middle Aged Myocardial Infarction/blood/genetics Neuregulins/genetics Pakistan Pedigree *Phenotype Phosphoproteins/genetics Postprandial Period RNA Splice Sites/genetics Reverse Genetics/methods Sodium-Hydrogen Exchangers/genetics Triglycerides/blood A major goal of biomedicine is to understand the function of every gene in the human genome. Loss-of-function mutations can disrupt both copies of a given gene in humans and phenotypic analysis of such 'human knockouts' can provide insight into gene function. Consanguineous unions are more likely to result in offspring carrying homozygous loss-of-function mutations. In Pakistan, consanguinity rates are notably high. Here we sequence the protein-coding regions of 10,503 adult participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS), designed to understand the determinants of cardiometabolic diseases in individuals from South Asia. We identified individuals carrying homozygous predicted loss-of-function (pLoF) mutations, and performed phenotypic analysis involving more than 200 biochemical and disease traits. We enumerated 49,138 rare (1.5-fold change between 8 and 40 weeks of gestation; and (2) a false discovery rate-adjusted value of P 2 fold changes in dystrophic serum abundance. A large majority of previously described biomarkers (ANP32B, THBS4, CAMK2A/B/D, CYCS, CAPNI) were normalised towards wild-type levels in Fiona animals. This work also identified potential mdx markers specific to increased utrophin (DUS3, TPI1) and highlights novel mdx biomarkers (GITR, MYBPC1, HSP60, SIRT2, SMAD3, CNTN1). We define a panel of putative protein mdx biomarkers to evaluate utrophin based strategies which may help to accelerate their translation to the clinic. Guiraud, Simon Edwards, Benjamin Squire, Sarah E Babbs, Arran Shah, Nandini Berg, Adam Chen, Huijia Davies, Kay E eng MR/N/1/MRC_/Medical Research Council/United Kingdom Research Support, Non-U.S. Gov't England Sci Rep. Mar 2;7:. doi: 10./srep.I SomaScan 03/03/ Suhre K, et al. Connecting genetic risk to disease end points through the human blood plasma proteome Nat Commun 8 https://www.doi.org/10./ncomms 28,240,269 Alleles Blood Proteins/*metabolism Complement System Proteins/metabolism Drug Delivery Systems *Endpoint Determination Gene Regulatory Networks *Genetic Predisposition to Disease Genetic Variation Genome, Human Genome-Wide Association Study Glycoproteins/metabolism Heme/metabolism Humans Molecular Sequence Annotation Pharmacogenetics Protein Processing, Post-Translational/genetics Proteome/genetics/*metabolism Quantitative Trait Loci RNA Splicing/genetics RNA, Messenger/genetics/metabolism Reproducibility of Results Risk Factors Genome-wide association studies (GWAS) with intermediate phenotypes, like changes in metabolite and protein levels, provide functional evidence to map disease associations and translate them into clinical applications. However, although hundreds of genetic variants have been associated with complex disorders, the underlying molecular pathways often remain elusive. Associations with intermediate traits are key in establishing functional links between GWAS-identified risk-variants and disease end points. Here we describe a GWAS using a highly multiplexed aptamer-based affinity proteomics platform. We quantify 539 associations between protein levels and gene variants (pQTLs) in a German cohort and replicate over half of them in an Arab and Asian cohort. Fifty-five of the replicated pQTLs are located in trans. Our associations overlap with 57 genetic risk loci for 42 unique disease end points. We integrate this information into a genome-proteome network and provide an interactive web-tool for interrogations. Our results provide a basis for novel approaches to pharmaceutical and diagnostic applications. Suhre, Karsten Arnold, Matthias Bhagwat, Aditya Mukund Cotton, Richard J Engelke, Rudolf Raffler, Johannes Sarwath, Hina Thareja, Gaurav Wahl, Annika DeLisle, Robert Kirk Gold, Larry Pezer, Marija Lauc, Gordan El-Din Selim, Mohammed A Mook-Kanamori, Dennis O Al-Dous, Eman K Mohamoud, Yasmin A Malek, Joel Strauch, Konstantin Grallert, Harald Peters, Annette Kastenmuller, Gabi Gieger, Christian Graumann, Johannes eng Research Support, Non-U.S. Gov't England Nat Commun. Feb 27;8:. doi: 10./ncomms.I SomaScan 02/28/ Trausch JJ, et al. Development and Characterization of an HPV Type-16 Specific Modified DNA Aptamer for the Improvement of Potency Assays Anal Chem 89 6 - https://www.doi.org/10./acs.analchem.6b 28,233,502 Antigen-Antibody Reactions Antigens, Viral/*immunology Aptamers, Nucleotide/chemical synthesis/chemistry/*immunology Enzyme-Linked Immunosorbent Assay Epitopes/*immunology Human papillomavirus 16/*immunology Humans Papillomavirus Vaccines/*immunology Measuring vaccine potency is critical for vaccine release and is often accomplished using antibody-based ELISAs. Antibodies can be associated with significant drawbacks that are often overlooked including lot-to-lot variability, problems with cell-line maintenance, limited stability, high cost, and long discovery lead times. Here, we address many of these issues through the development of an aptamer, known as a slow off-rate modified DNA aptamer (SOMAmer), which targets a vaccine antigen in the human papillomavirus (HPV) vaccine Gardasil. The aptamer, termed HPV-07, was selected to bind the Type 16 virus-like-particle (VLP) formed by the self-assembling capsid protein L1. It is capable of binding with high sensitivity (EC(50) of 0.1 to 0.4 mug/mL depending on assay format) while strongly discriminating against other VLP types. The aptamer competes for binding with the neutralizing antibody H16.V5, indicating at least partial recognition of a neutralizing and clinically relevant epitope. This makes it a useful reagent for measuring both potency and stability. When used in an ELISA format, the aptamer displays both high precision (intermediate precision of 6.3%) and a large linear range spanning from 25% to 200% of a typical formulation. To further exploit the advantages of aptamers, a simplified mix and read assay was also developed. This assay format offers significant time and resource reductions compared to a traditional ELISA. These results show aptamers are suitable reagents for biological potency assays, and we expect that their implementation could improve upon current assay formats. Trausch, Jeremiah J Shank-Retzlaff, Mary Verch, Thorsten eng Research Support, Non-U.S. Gov't Anal Chem. Mar 21;89(6):-. doi: 10./acs.analchem.6b. Epub Mar 8.I SomaScan 02/25/ van den Broek TJ, et al. The impact of micronutrient status on health: correlation network analysis to understand the role of micronutrients in metabolic-inflammatory processes regulating homeostasis and phenotypic flexibility Genes Nutr 12 5 https://www.doi.org/10./s-017--7 28,194,237 Carotenoids Glucose Inflammation Lipid Metabolic challenge test Phenotypic flexibility Systems biology Vitamins BACKGROUND: Vitamins and carotenoids are key micronutrients facilitating the maintenance of health, as evidenced by the increased risk of disease with low intake. Optimal phenotypic flexibility, i.e., the ability to respond to a physiological challenge, is an essential indicator of health status. Therefore, health can be measured by applying a challenge test and monitoring the response of relevant phenotypic processes. In this study, we assessed the correlation of three fat-soluble vitamins, (i.e., vitamin A or retinol, vitamin D(3), two homologues of vitamin E) and four carotenoids (i.e., alpha-carotene, beta-carotene, beta-cryptoxanthin, and lycopene), with characteristics of metabolic and inflammatory parameters at baseline and in response to a nutritional challenge test (NCT) in a group of 36 overweight and obese male subjects, using proteomics and metabolomics platforms. The phenotypic flexibility concept implies that health can be measured by the ability to adapt to a NCT, which may offer a more sensitive way to assess changes in health status of healthy subjects. RESULTS: Correlation analyses of results after overnight fasting revealed a rather evenly distributed network in a number of relatively strong correlations per micronutrient, with minor overlap between correlation profiles of each compound. Correlation analyses of challenge response profiles for metabolite and protein parameters with micronutrient status revealed a network that is more skewed towards alpha-carotene and gamma-tocopherol suggesting a more prominent role for these micronutrients in the maintenance of phenotypic flexibility. Comparison of the networks revealed that there is merely overlap of two parameters (inositol and oleic acid (C18:1)) affirming that there is a specific biomarker response profile upon NCT. CONCLUSIONS: Our study shows that applying the challenge test concept is able to reveal previously unidentified correlations between specific micronutrients and health-related processes, with potential relevance for maintenance of health that were not observed by correlating homeostatic measurements. This approach will contribute to insights on the influence of micronutrients on health and help to create efficient micronutrient intervention programs. van den Broek, Tim J Kremer, Bas H A Marcondes Rezende, Marisa Hoevenaars, Femke P M Weber, Peter Hoeller, Ulrich van Ommen, Ben Wopereis, Suzan eng Germany Genes Nutr. Feb 8;12:5. doi: 10./s-017--7. eCollection .I SomaScan 02/15/ Di Narzo AF, et al. High-Throughput Characterization of Blood Serum Proteomics of IBD Patients with Respect to Aging and Genetic Factors PLoS Genet 13 1 e https://www.doi.org/10./journal.pgen. 28,129,359 Adult Aging/*blood Biomarkers/blood Case-Control Studies Female *Genetic Predisposition to Disease Hepatocyte Growth Factor/blood High-Throughput Screening Assays Humans Inflammatory Bowel Diseases/*blood/epidemiology/genetics Male Middle Aged Polymorphism, Single Nucleotide Proteome/genetics/*metabolism Proto-Oncogene Proteins/blood Quantitative Trait Loci To date, no large scale, systematic description of the blood serum proteome has been performed in inflammatory bowel disease (IBD) patients. By using microarray technology, a more complete description of the blood proteome of IBD patients is feasible. It may help to achieve a better understanding of the disease. We analyzed blood serum profiles of proteins in IBD patients of European descent (84 Crohn's Disease (CD) subjects and 88 Ulcerative Colitis (UC) subjects) as well as 15 healthy control subjects, and linked protein variability to patient age (all cohorts) and genetic components (genotype data generated from CD patients). We discovered new, previously unreported aging-associated proteomic traits (such as serum Albumin level), confirmed previously reported results from different tissues (i.e., upregulation of APOE with aging), and found loss of regulation of MMP7 in CD patients. In carrying out a genome wide genotype-protein association study (proteomic Quantitative Trait Loci, pQTL) within the CD patients, we identified 41 distinct proteomic traits influenced by cis pQTLs (underlying SNPs are referred to as pSNPs). Significant overlaps between pQTLs and cis eQTLs corresponding to the same gene were observed and in some cases the QTL were related to inflammatory disease susceptibility. Importantly, we discovered that serum protein levels of MST1 (Macrophage Stimulating 1) were regulated by SNP rs (p = 5.96E-10, FDR500 clinical trials currently registered with the NIH. Tissue-derived MSC require invasive harvesting and imply donor-to-donor differences, to which embryonic stem cell (ESC)-derived MSC may provide an alternative and thus warrant thorough characterization. In continuation of our previous study where we compared in depth embryonic stem cells (ESC) and MSC from two sources (bone marrow and ESC-derived), we included the aptamer-based SOMAscan assay, complementing LC-MS/MS and RNA-seq data. Furthermore, SOMAscan, a targeted proteomics platform developed for analyzing clinical samples, has been benchmarked against established analytical platforms (LC-MS/MS and RNA-seq) using stem cell comparisons as a model. Billing, Anja M Ben Hamidane, Hisham Bhagwat, Aditya M Cotton, Richard J Dib, Shaima S Kumar, Pankaj Hayat, Shahina Goswami, Neha Suhre, Karsten Rafii, Arash Graumann, Johannes eng Netherlands J Proteomics. Jan 6;150:86-97. doi: 10./j.jprot..08.023. Epub Sep 6.I SomaScan 10/25/ Qiao Z, et al. Proteomic study of hepatocellular carcinoma using a novel modified aptamer-based array (SOMAscan) platform Biochim Biophys Acta Proteins Proteom 4 434-443 https://www.doi.org/10./j.bbapap..09.011 27,663,888 Aptamers, Nucleotide/*chemistry *Carcinoma, Hepatocellular/genetics/metabolism Female *Gene Expression Regulation, Neoplastic Humans *Liver Neoplasms/genetics/metabolism Male *Neoplasm Proteins/biosynthesis/genetics Oligonucleotide Array Sequence Analysis/*methods Hepatocellular carcinoma SOMAscan Vascular invasion Vascular invasion is a pathological hallmark of hepatocellular carcinoma (HCC), associated with poor prognosis; it is strongly related to the early recurrence and poor survival after curative resection. In order to determine the proteomic backgrounds of HCC carcinogenesis and vascular invasion, we employed a novel modified aptamer-based array (SOMAscan) platform. SOMAscan is based on the Slow Off-rate Modified Aptamers (SOMAmers), which rely on the natural 3D folding of single-stranded DNA-based protein affinity reagents. Currently, the expression level of proteins can be assessed quantitatively. Correlation matrix analysis showed that the overall proteomic features captured by SOMAscan differ between tumor and non-tumor tissues. Non-tumor tissues were shown to have more homogeneous proteome backgrounds than tumor tissues. A comparative study identified 68 proteins with differential expression between tumor and non-tumor tissues, together with eight proteins associated with vascular invasion. Gene Ontology analysis showed that the extracellular space and extracellular region proteins were predominantly detected. Network analysis revealed the linkage of seven proteins, AKT1, MDM2, PTEN, FGF1, MAPK8, PRKCB, and FN1, which were categorized as the components of Pathways in cancer" in pathway analysis. The results of SOMAscan analysis were not concordant with those obtained by western blotting; only the determined FN1 levels were concordant between the two platforms. We demonstrated that the proteome captured by SOMAscan includes the proteins relevant to carcinogenesis and vascular invasion in HCC. The identified proteins may serve as candidates for the future studies of disease mechanisms and clinical applications." Qiao, Zhiwei Pan, Xiaoqing Parlayan, Cuneyd Ojima, Hidenori Kondo, Tadashi eng Research Support, Non-U.S. Gov't Netherlands Biochim Biophys Acta Proteins Proteom. Apr;(4):434-443. doi: 10./j.bbapap..09.011. Epub Sep 20.I SomaScan 09/25/ Rice LM, et al. A Proteome-Derived Longitudinal Pharmacodynamic Biomarker for Diffuse Systemic Sclerosis Skin J Invest Dermatol 137 1 62-70 https://www.doi.org/10./j.jid..08.027 27,640,094 Adult Biomarkers/blood Case-Control Studies Cytokines/*metabolism Enzyme-Linked Immunosorbent Assay Female Humans Linear Models Longitudinal Studies Male Middle Aged Pharmacogenomic Testing Proteome/*metabolism Reproducibility of Results Scleroderma, Diffuse/*blood/drug therapy/physiopathology Severity of Illness Index In this study we systematically investigated alterations in the serum proteome of patients with diffuse cutaneous systemic sclerosis and identified differentially expressed proteins that correlated with disease severity. Our goal was to identify a combination of serum proteins that would provide a biological measure for the extent of skin disease and that could be combined into a longitudinal pharmacodynamic biomarker. We found that 16% of the sera proteins analyzed by SOMAscan aptamer technology, from two cohorts of patients with diffuse cutaneous systemic sclerosis, were identified as differentially regulated between diffuse cutaneous systemic sclerosis and controls and correlated with modified Rodnan skin score. This dataset showed tumor necrosis factor-alpha, IFN-gamma, transforming growth factor-beta, and IL-13 as potential upstream regulators of the serum protein patterns in the sera of patients with diffuse cutaneous systemic sclerosis. By ELISA, two analytes (ST2 and Spondin-1) best described longitudinal change in modified Rodnan skin score, using linear mixed models. This model was then validated in three independent cohorts. In this study we discovered a large array of proteins not previously associated with systemic sclerosis that provide insight into pathogenesis and potential targets for therapeutic intervention. Furthermore, we show that two of these proteins can be combined to form a robust longitudinal biomarker that might be used in clinical trials to assess changes in diffuse cutaneous systemic sclerosis skin disease over time. Rice, Lisa M Mantero, Julio C Stifano, Giuseppina Ziemek, Jessica Simms, Robert W Gordon, Jessica Domsic, Robyn Lafyatis, Robert eng UL1 TR/TR/NCATS NIH HHS/ P30 AR/AR/NIAMS NIH HHS/ P50 AR/AR/NIAMS NIH HHS/ R01 AR/AR/NIAMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't J Invest Dermatol. Jan;137(1):62-70. doi: 10./j.jid..08.027. Epub Sep 14.I SomaScan 09/19/ Escolano JM, et al. Selection of aptamers to Neisseria meningitidis and Streptococcus pneumoniae surface specific proteins and affinity assay using thin film AlN resonators Sensors and Actuators B: Chemical 246 591-596 https://www.doi.org/10./j.snb..02.098 Meningitis SOMAmer AlN gravimetric biosensor PavA FHbp The first steps in the development of an aptasensor for bacterial meningitis diagnosis in real time are described: slow off-rate modified aptamers (SOMAmer) selection, gravimetric sensor fabrication and functionalization of its active surface. SOMAmers polyclonal populations were generated to surface specific proteins PavA (S. pneumoniae) and FHbp (N. meningitidis) by systematic evolution of ligands by exponential enrichment method (SELEX). After eight rounds, they were tested by direct enzyme-linked oligonucleotide assays (ELONA) and by high frequency (1.4GHz) gravimetric sensors based on thin film AlN resonators operating in shear mode. The sensing surface of the resonators was functionalized using a silane-glutaraldehyde based protocol and the binding of PavA and FHbp was measured in real time. The SOMAmers polyclonal populations showing the best ELONA results have been also tested using gravimetric sensors and the binding to the protein functionalized surface was measured in real time showing positive results. These first steps towards the development of an aptasensor for the targeted bacteria demonstrate the potential of the method for sensitive, rapid, and cost effective detection of bacterial meningitis. Escolano, José M. Díaz-Durán, Bárbara DeMiguel-Ramos, Mario Olivares, Jimena Geday, Morten A. Iborra, Enrique SomaScan Tsim S, et al. Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma (DIAPHRAGM) study: protocol of a prospective, multicentre, observational study BMJ Open 6 11 e https://www.doi.org/10./bmjopen-- 27,884,852 Biomarkers, Tumor/blood Cross-Sectional Studies Extracellular Matrix Proteins/*blood GPI-Linked Proteins/*blood Humans Lung Neoplasms/*blood/*diagnostic imaging Magnetic Resonance Imaging Mesothelin Mesothelioma/*blood/*diagnostic imaging Mesothelioma, Malignant Prognosis Prospective Studies Proteomics/methods ROC Curve Research Design Scotland Biomarker Diagnosis Mesothelioma INTRODUCTION: Malignant pleural mesothelioma (MPM) is an asbestos-related cancer, which is difficult to diagnose. Thoracoscopy is frequently required but is not widely available. An accurate, non-invasive diagnostic biomarker would allow early specialist referral, limit diagnostic delays and maximise clinical trial access. Current markers offer insufficient sensitivity and are not routinely used. The SOMAmer proteomic classifier and fibulin-3 have recently demonstrated sensitivity and specificity exceeding 90% in retrospective studies. DIAPHRAGM (Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma) is a suitably powered, multicentre, prospective observational study designed to determine whether these markers provide clinically useful diagnostic and prognostic information. METHODS AND ANALYSIS: Serum and plasma (for SOMAscan and fibulin-3, respectively) will be collected at presentation, prior to pleural biopsy/pleurodesis, from 83 to 120 patients with MPM, at least 480 patients with non-MPM pleural disease and 109 asbestos-exposed controls. Final numbers of MPM/non-MPM cases will depend on the incidence of MPM in the study population (estimated at 13-20%). Identical sampling and storage protocols will be used in 22 recruiting centres and histological confirmation sought in all cases. Markers will be measured using the SOMAscan proteomic assay (SomaLogic) and a commercially available fibulin-3 ELISA (USCN Life Science). The SE in the estimated sensitivity and specificity will be 4 log10 units) and an ultralow detection limit of 0.67 fM (0.012 pg/mL). These results show comparable sensitivity to our antibody pair-based Simoa assays, and tens to thousands-fold enhancement in sensitivity compared with conventional ELISAs. High recovery percentages were observed in a spike-recovery test using human sera, demonstrating the feasibility of this novel Simoa assay in detecting TNF-alpha in clinically relevant samples. Detection SOMAmers were also used to detect other cytokines, such as IFN-gamma, IL-1beta, IL-2, IL-6, and IL-10, in human samples. Although not yet demonstrated, in principle it should be possible to eventually replace both the capture and detector antibodies with corresponding SOMAmer pairs in sandwich immunoassays. The combination of the ultrasensitive Simoa platform with the higher reliability of SOMAmer binding reagents will greatly benefit both biomarker discovery and disease diagnostic fields. Wu, Danlu Katilius, Evaldas Olivas, Edgar Dumont Milutinovic, Milena Walt, David R eng Letter Research Support, U.S. Gov't, Non-P.H.S. Anal Chem. Sep 6;88(17):-9. doi: 10./acs.analchem.6b. Epub Aug 23.I SomaScan 08/17/ Ashley SL, et al. Six-SOMAmer Index Relating to Immune, Protease and Angiogenic Functions Predicts Progression in IPF PLoS One 11 8 e https://www.doi.org/10./journal.pone. 27,490,795 Aged Area Under Curve Biomarkers/blood Cathepsins/metabolism Cysteine Endopeptidases/metabolism Disease Progression Disease-Free Survival Female Humans Idiopathic Pulmonary Fibrosis/immunology/metabolism/*pathology Inducible T-Cell Co-Stimulator Protein/metabolism Lectins/metabolism Logistic Models Male Middle Aged Peptide Hydrolases/*metabolism Proportional Hazards Models ROC Curve *Severity of Illness Index Smoking Vascular Endothelial Growth Factor Receptor-2/metabolism RATIONALE: Biomarkers in easily accessible compartments like peripheral blood that can predict disease progression in idiopathic pulmonary fibrosis (IPF) would be clinically useful regarding clinical trial participation or treatment decisions for patients. In this study, we used unbiased proteomics to identify relevant disease progression biomarkers in IPF. METHODS: Plasma from IPF patients was measured using an analyte slow off-rate modified aptamer (SOMAmer) array, and patient outcomes were followed over the next 80 weeks. Receiver operating characteristic (ROC) curves evaluated sensitivity and specificity for levels of each biomarker and estimated area under the curve (AUC) when prognostic biomarker thresholds were used to predict disease progression. Both logistic and Cox regression models advised biomarker selection for a composite disease progression index; index biomarkers were weighted via expected progression-free days lost during follow-up with a biomarker on the unfavorable side of the threshold. RESULTS: A six-analyte index, scaled 0 to 11, composed of markers of immune function, proteolysis and angiogenesis [high levels of ficolin-2 (FCN2), cathepsin-S (Cath-S), legumain (LGMN) and soluble vascular endothelial growth factor receptor 2 (VEGFsR2), but low levels of inducible T cell costimulator (ICOS) or trypsin 3 (TRY3)] predicted better progression-free survival in IPF with a ROC AUC of 0.91. An index score >/= 3 (group >/= 2) was strongly associated with IPF progression after adjustment for age, gender, smoking status, immunomodulation, forced vital capacity % predicted and diffusing capacity for carbon monoxide % predicted (HR 16.8, 95% CI 2.2-126.7, P = 0.006). CONCLUSION: This index, derived from the largest proteomic analysis of IPF plasma samples to date, could be useful for clinical decision making in IPF, and the identified analytes suggest biological processes that may promote disease progression. Ashley, Shanna L Xia, Meng Murray, Susan O'Dwyer, David N Grant, Ethan White, Eric S Flaherty, Kevin R Martinez, Fernando J Moore, Bethany B eng R01 HL/HL/NHLBI NIH HHS/ T32 AI/AI/NIAID NIH HHS/ UL1 TR/TR/NCATS NIH HHS/ PLoS One. Aug 4;11(8):e. doi: 10./journal.pone.. eCollection .I SomaScan 08/05/ Gramolini A, et al. Identifying Low-Abundance Biomarkers: Aptamer-Based Proteomics Potentially Enables More Sensitive Detection in Cardiovascular Diseases Circulation 134 4 286-9 https://www.doi.org/10./CIRCULATIONAHA.116. 27,444,931 *Biomarkers Biomarkers, Tumor Cardiovascular Diseases/diagnosis Humans *Proteomics Editorials biomarkers cohort studies diagnosis prognosis proteomics Gramolini, Anthony Lau, Edward Liu, Peter P eng CIHR/Canada Comment Editorial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Circulation. Jul 26;134(4):286-9. doi: 10./CIRCULATIONAHA.116..I SomaScan 07/23/ Ngo D, et al. Aptamer-Based Proteomic Profiling Reveals Novel Candidate Biomarkers and Pathways in Cardiovascular Disease Circulation 134 4 270-85 https://www.doi.org/10./CIRCULATIONAHA.116. 27,444,932 Acute Coronary Syndrome/blood Adult Aptamers, Nucleotide/*metabolism Biomarkers/*blood Blood Proteins/*analysis Cardiomyopathy, Hypertrophic/*blood/complications Chromatography, Liquid DNA, Single-Stranded/metabolism Female Humans Longitudinal Studies Male Middle Aged Myocardial Infarction/*blood/etiology Phenotype Proteomics/*methods Reproducibility of Results Sensitivity and Specificity Tandem Mass Spectrometry aptamer, nucleotides cardiovascular diseases mass spectrometry myocardial infarction proteomics BACKGROUND: Single-stranded DNA aptamers are oligonucleotides of approximately 50 base pairs in length selected for their ability to bind proteins with high specificity and affinity. Emerging DNA aptamer-based technologies may address limitations of existing proteomic techniques, including low sample throughput, which have hindered proteomic analyses of large cohorts. METHODS: To identify early biomarkers of myocardial injury, we applied an aptamer-based proteomic platform that measures proteins to a clinically relevant perturbational model of planned myocardial infarction (PMI), patients undergoing septal ablation for hypertrophic cardiomyopathy. Blood samples were obtained before and at 10 and 60 minutes after PMI, and protein changes were assessed by repeated-measures analysis of variance. The generalizability of our PMI findings was evaluated in a spontaneous myocardial infarction cohort (Wilcoxon rank-sum). We then tested the platform's ability to detect associations between proteins and Framingham Risk Score components in the Framingham Heart Study, performing regression analyses for each protein versus each clinical trait. RESULTS: We found 217 proteins that significantly changed in the peripheral vein blood after PMI in a derivation cohort (n=15; P/= 2(8) and increased IL-6 and CXCL10 to healthy controls, we identified 162 differentially-expressed proteins between the two groups. This number greatly exceeds the number of DEPs identified in previous studies in human influenza patients. Most of the identified proteins were associated with the host immune response to infection, and changes in protein levels of 151 of the DEPs were significantly correlated with viral load. Most important, SOMAscan identified differentially expressed proteins heretofore not associated with respiratory influenza infection in humans. Our study is the first report for the use of SOMAscan to screen nasal secretions. It establishes a precedent for micro-proteomic quantification of proteins that reflect ongoing response to respiratory infection. Marion, Tony Elbahesh, Husni Thomas, Paul G DeVincenzo, John P Webby, Richard Schughart, Klaus eng HHSNC/AI/NIAID NIH HHS/ HHSNC/AI/NIAID NIH HHS/ HHSNC/PHS HHS/ HHSNC/PHS HHS/ Comparative Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. PLoS One. Apr 18;11(4):e. doi: 10./journal.pone.. eCollection .I SomaScan 04/19/ Hathout Y, et al. Clinical utility of serum biomarkers in Duchenne muscular dystrophy Clin Proteomics 13 9 https://www.doi.org/10./s-016--x 27,051,355 Biomarkers Clinical outcomes Duchenne muscular dystrophy Mass spectrometry Pharmacodynamic biomarkers Proteins SomaScan Surrogate biomarkers miRNA Assessments of disease progression and response to therapies in Duchenne muscular dystrophy (DMD) patients remain challenging. Current DMD patient assessments include complex physical tests and invasive procedures such as muscle biopsies, which are not suitable for young children. Defining alternative, less invasive and objective outcome measures to assess disease progression and response to therapy will aid drug development and clinical trials in DMD. In this review we highlight advances in development of non-invasive blood circulating biomarkers as a means to assess disease progression and response to therapies in DMD. Hathout, Yetrib Seol, Haeri Han, Meng Hsuan J Zhang, Aiping Brown, Kristy J Hoffman, Eric P eng U54 HD/HD/NICHD NIH HHS/ P30 HD/HD/NICHD NIH HHS/ R01 AR/AR/NIAMS NIH HHS/ P50 AR/AR/NIAMS NIH HHS/ U54 HD/HD/NICHD NIH HHS/ Review England Clin Proteomics. Apr 5;13:9. doi: 10./s-016--x. eCollection .I SomaScan 04/07/ Gelinas AD, et al. Embracing proteins: structural themes in aptamer-protein complexes Curr Opin Struct Biol 36 122-32 https://www.doi.org/10./j.sbi..01.009 26,919,170 Aptamers, Nucleotide/*chemistry/metabolism Binding Sites Hydrophobic and Hydrophilic Interactions Ligands *Models, Molecular Nucleic Acid Conformation Nucleotide Motifs Protein Binding Protein Conformation Proteins/*chemistry/metabolism Structure-Activity Relationship Understanding the structural rules that govern specific, high-affinity binding characteristic of aptamer-protein interactions is important in view of the increasing use of aptamers across many applications. From the modest number of 16 aptamer-protein structures currently available, trends are emerging. The flexible phosphodiester backbone allows folding into precise three-dimensional structures using known nucleic acid motifs as scaffolds that orient specific functional groups for target recognition. Still, completely novel motifs essential for structure and function are found in modified aptamers with diversity-enhancing side chains. Aptamers and antibodies, two classes of macromolecules used as affinity reagents with entirely different backbones and composition, recognize protein epitopes of similar size and with comparably high shape complementarity. Gelinas, Amy D Davies, Douglas R Janjic, Nebojsa eng Review England Curr Opin Struct Biol. Feb;36:122-32. doi: 10./j.sbi..01.009. Epub Feb 24.I SomaScan 02/27/ Drolet DW, et al. Fit for the Eye: Aptamers in Ocular Disorders Nucleic Acid Ther 26 3 127-46 https://www.doi.org/10./nat.. 26,757,406 Aptamers, Nucleotide/*therapeutic use Eye Diseases/genetics/*therapy Humans Ligands Ophthalmology/*trends SELEX Aptamer Technique/*trends For any new class of therapeutics, there are certain types of indications that represent a natural fit. For nucleic acid ligands in general, and aptamers in particular, the eye has historically been an attractive site for therapeutic intervention. In this review, we recount the discovery and early development of three aptamers designated for use in ophthalmology, one approved (Macugen), and two in late-stage development (Fovista and Zimura). Every one of these molecules was originally intended for other indications. Key improvements in technology, specifically with regard to libraries used for in vitro selection and subsequent chemical optimization of aptamers, have played an important role in allowing the identification of development candidates with suitable properties. The lessons learned from the selection of these molecules are valuable for informing us about the many remaining opportunities for aptamer-based therapeutics in ophthalmology as well as for identifying additional indications for which aptamers as a class of therapeutics have distinct advantages. Drolet, Daniel W Green, Louis S Gold, Larry Janjic, Nebojsa eng Review Nucleic Acid Ther. Jun;26(3):127-46. doi: 10./nat... Epub Jan 12.I SomaScan 01/13/ Murota A, et al. Serum proteomic analysis identifies interleukin 16 as a biomarker for clinical response during early treatment of rheumatoid arthritis Cytokine 78 87-93 https://www.doi.org/10./j.cyto..12.002 26,700,586 Abatacept/therapeutic use Adult Aged Antibodies, Monoclonal, Humanized/therapeutic use Antirheumatic Agents/*therapeutic use Arthritis, Rheumatoid/*blood/*drug therapy Biomarkers/blood Blood Proteins/*analysis/immunology Blood Sedimentation Female Humans Infliximab/therapeutic use Interleukin-16/*blood Male Matrix Metalloproteinase 3/blood Methotrexate/therapeutic use Middle Aged *Proteomics Statistics as Topic Treatment Outcome Biomarker Interleukin-16 Proteomics Rheumatoid arthritis Serum protein OBJECTIVES: To conduct a comprehensive quantitative proteomics analysis of novel serum protein biomarkers based on synovitis status associated with matrix metalloproteinase-3 (MMP-3) and to determine the clinical significance of these biomarkers in rheumatoid arthritis (RA). METHODS: Patients with untreated RA (n=28), primary Sjogren's syndrome (pSS) (n=30), and healthy controls (HCs) (n=30) were enrolled for the screening assay. A total of serum proteins were analyzed using the SOMAscan assay. Serum levels of MMP-3 and interleukin (IL)-16 were measured using a latex turbidimetric immunoassay and ELISA at baseline and 12weeks after treatment with methotrexate (MTX) for MTX-naive RA patients (n=28) or with the biologics tocilizumab (TCZ) (n=7), abatacept (ABT) (n=11) or infliximab (n=22) for MTX-inadequate response (IR) RA patients. Correlation analysis was conducted using Spearman's rank correlation method. RESULTS: Proteomics showed that serum IL-16 levels were most positively correlated with those of MMP-3 (rho=0.51, p99 percentile of the controls) was significantly increased (17 to 23%). Measurement reproducibility of these results was confirmed by an ELISA for fibrinogen (Pearson's r = 0.77). In an independent sample set from 36 patients and 30 controls, using the ELISA, results were similar (22%). When these two sample sets were combined, the number of patients with a high fibrinogen level was significantly increased (15/66; odds ratio 8.53; 95% confidence interval 1.9-39.1, p = 0.). By using diffusion tensor imaging, we found white matter tracts abnormalities in patients with a high fibrinogen level but not those patients with a normal fibrinogen level, compared with controls. Plasma fibrinogen levels were similar among the diagnostic groups. Our results point to a subgroup of MDD represented by increased CSF fibrinogen and white matter tract abnormalities. Hattori, Kotaro Ota, Miho Sasayama, Daimei Yoshida, Sumiko Matsumura, Ryo Miyakawa, Tomoko Yokota, Yuuki Yamaguchi, Shinobu Noda, Takamasa Teraishi, Toshiya Hori, Hiroaki Higuchi, Teruhiko Kohsaka, Shinichi Goto, Yu-ichi Kunugi, Hiroshi eng Research Support, Non-U.S. Gov't England Sci Rep. Jun 17;5:. doi: 10./srep.I SomaScan 06/18/ Kiddle SJ, et al. Plasma protein biomarkers of Alzheimer's disease endophenotypes in asymptomatic older twins: early cognitive decline and regional brain volumes Transl Psychiatry 5 6 e584 https://www.doi.org/10./tp..78 26,080,319 Aged Alzheimer Disease/*blood/pathology Asymptomatic Diseases Biomarkers/blood Brain/*pathology *Endophenotypes Entorhinal Cortex/pathology Female Humans Intracellular Signaling Peptides and Proteins/*blood MAP Kinase Kinase 4/*blood Male Middle Aged Neuropsychological Tests Organ Size Protein Serine-Threonine Kinases/*blood Twins/*genetics/psychology There is great interest in blood-based markers of Alzheimer's disease (AD), especially in its pre-symptomatic stages. Therefore, we aimed to identify plasma proteins whose levels associate with potential markers of pre-symptomatic AD. We also aimed to characterise confounding by genetics and the effect of genetics on blood proteins in general. Panel-based proteomics was performed using SOMAscan on plasma samples from TwinsUK subjects who are asymptomatic for AD, measuring the level of proteins. Protein levels were compared with 10-year change in CANTAB-paired associates learning (PAL; n = 195), and regional brain volumes (n = 34). Replication of proteins associated with regional brain volumes was performed in 254 individuals from the AddNeuroMed cohort. Across all the proteins measured, genetic factors were found to explain ~26% of the variability in blood protein levels on average. The plasma level of the mitogen-activated protein kinase (MAPK) MAPKAPK5 protein was found to positively associate with the 10-year change in CANTAB-PAL in both the individual and twin difference context. The plasma level of protein MAP2K4 was found to suggestively associate negatively (Q 100 proteins) blood proteomics studies of AD, which had identified a total of 163 candidate biomarkers. Few putative blood-based protein biomarkers replicate in independent studies but we found that some proteins do appear in multiple studies; for example, four candidate biomarkers are found to associate with AD-related phenotypes in five independent research cohorts in these 21 studies: alpha-1-antitrypsin, alpha-2-macroglobulin, apolipoprotein E, and complement C3. Using SomaLogic's SOMAscan proteomics technology, we were able to conduct a large-scale replication study for 94 of the 163 candidate biomarkers from these 21 published studies in plasma samples from 677 subjects from the AddNeuroMed (ANM) and the Alzheimer's Research UK/Maudsley BRC Dementia Case Registry at King's Health Partners (ARUK/DCR) research cohorts. Nine of the 94 previously reported candidates were found to associate with AD-related phenotypes (False Discovery Rate (FDR) q-value 3 logs, an overall dynamic range of at least 7 logs, and a throughput of one million analytes per week. Our collection includes SOMAmers that specifically recognize most of the complement cascade proteins. We have used this assay to identify potential biomarkers in a range of diseases such as malignancies, cardiovascular disorders, and inflammatory conditions. In this chapter, we describe the application of our technology to discovering large-scale protein expression changes associated with chronic kidney disease and non-small cell lung cancer. With this new proteomics technology-which is fast, economical, highly scalable, and flexible--we now have a powerful tool that enables whole-proteome proteomics, biomarker discovery, and advancing the next generation of evidence-based, "personalized" diagnostics and therapeutics." Mehan, Michael R Ostroff, Rachel Wilcox, Sheri K Steele, Fintan Schneider, Daniel Jarvis, Thale C Baird, Geoffrey S Gold, Larry Janjic, Nebojsa eng Review Adv Exp Med Biol. ;735:283-300. doi: 10./978-1---2_20.I SomaScan 02/14/ Davies DR, et al. Unique motifs and hydrophobic interactions shape the binding of modified DNA ligands to protein targets Proc Natl Acad Sci U S A 109 49 -6 https://www.doi.org/10./pnas. 23,139,410 Amino Acid Motifs/genetics Aptamers, Nucleotide/*chemistry/*metabolism Becaplermin Crystallography, X-Ray DNA Primers/genetics *Hydrophobic and Hydrophilic Interactions *Models, Molecular Molecular Sequence Data Molecular Structure Phosphorylation Protein Binding Proto-Oncogene Proteins c-sis/chemistry/*metabolism SELEX Aptamer Technique/*methods Sequence Analysis, DNA Transition Temperature Selection of aptamers from nucleic acid libraries by in vitro evolution represents a powerful method of identifying high-affinity ligands for a broad range of molecular targets. Nevertheless, a sizeable fraction of proteins remain difficult targets due to inherently limited chemical diversity of nucleic acids. We have exploited synthetic nucleotide modifications that confer protein-like diversity on a nucleic acid scaffold, resulting in a new generation of binding reagents called SOMAmers (Slow Off-rate Modified Aptamers). Here we report a unique crystal structure of a SOMAmer bound to its target, platelet-derived growth factor B (PDGF-BB). The SOMAmer folds into a compact structure and exhibits a hydrophobic binding surface that mimics the interface between PDGF-BB and its receptor, contrasting sharply with mainly polar interactions seen in traditional protein-binding aptamers. The modified nucleotides circumvent the intrinsic diversity constraints of natural nucleic acids, thereby greatly expanding the structural vocabulary of nucleic acid ligands and considerably broadening the range of accessible protein targets. Davies, Douglas R Gelinas, Amy D Zhang, Chi Rohloff, John C Carter, Jeffrey D O'Connell, Daniel Waugh, Sheela M Wolk, Steven K Mayfield, Wesley S Burgin, Alex B Edwards, Thomas E Stewart, Lance J Gold, Larry Janjic, Nebojsa Jarvis, Thale C eng Proc Natl Acad Sci U S A. Dec 4;109(49):-6. doi: 10./pnas.. Epub Nov 8.I SomaScan 11/10/ Ostroff RM, et al. Early detection of malignant pleural mesothelioma in asbestos-exposed individuals with a noninvasive proteomics-based surveillance tool PLoS One 7 10 e https://www.doi.org/10./journal.pone. 23,056,237 Adult Aged Aged, 80 and over Asbestos Biomarkers, Tumor/blood Carcinogens Case-Control Studies Cohort Studies Enzyme-Linked Immunosorbent Assay Female Humans Lectins/blood Male Mesothelioma/chemically induced/*diagnosis/metabolism Middle Aged Pleural Neoplasms/chemically induced/*diagnosis/metabolism Principal Component Analysis Proteomics/*methods Public Health Surveillance/*methods Reproducibility of Results Sensitivity and Specificity Young Adult BACKGROUND: Malignant pleural mesothelioma (MM) is an aggressive, asbestos-related pulmonary cancer that is increasing in incidence. Because diagnosis is difficult and the disease is relatively rare, most patients present at a clinically advanced stage where possibility of cure is minimal. To improve surveillance and detection of MM in the high-risk population, we completed a series of clinical studies to develop a noninvasive test for early detection. METHODOLOGY/PRINCIPAL FINDINGS: We conducted multi-center case-control studies in serum from 117 MM cases and 142 asbestos-exposed control individuals. Biomarker discovery, verification, and validation were performed using SOMAmer proteomic technology, which simultaneously measures over proteins in unfractionated biologic samples. Using univariate and multivariate approaches we discovered 64 candidate protein biomarkers and derived a 13-marker random forest classifier with an AUC of 0.99+/-0.01 in training, 0.98+/-0.04 in independent blinded verification and 0.95+/-0.04 in blinded validation studies. Sensitivity and specificity at our pre-specified decision threshold were 97%/92% in training and 90%/95% in blinded verification. This classifier accuracy was maintained in a second blinded validation set with a sensitivity/specificity of 90%/89% and combined accuracy of 92%. Sensitivity correlated with pathologic stage; 77% of Stage I, 93% of Stage II, 96% of Stage III and 96% of Stage IV cases were detected. An alternative decision threshold in the validation study yielding 98% specificity would still detect 60% of MM cases. In a paired sample set the classifier AUC of 0.99 and 91%/94% sensitivity/specificity was superior to that of mesothelin with an AUC of 0.82 and 66%/88% sensitivity/specificity. The candidate biomarker panel consists of both inflammatory and proliferative proteins, processes strongly associated with asbestos-induced malignancy. SIGNIFICANCE: The SOMAmer biomarker panel discovered and validated in these studies provides a solid foundation for surveillance and diagnosis of MM in those at highest risk for this disease. Ostroff, Rachel M Mehan, Michael R Stewart, Alex Ayers, Deborah Brody, Edward N Williams, Stephen A Levin, Stephen Black, Brad Harbut, Michael Carbone, Michele Goparaju, Chandra Pass, Harvey I eng U01 CA/CA/NCI NIH HHS/ 2U01CA-04/CA/NCI NIH HHS/ Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't PLoS One. ;7(10):e. doi: 10./journal.pone.. Epub Oct 3.I SomaScan 10/12/ Brody E, et al. Life's simple measures: unlocking the proteome J Mol Biol 422 5 595-606 https://www.doi.org/10./j.jmb..06.021 22,721,953 Aptamers, Nucleotide/*analysis/*metabolism Body Fluids/*chemistry Protein Binding Proteome/*analysis SELEX Aptamer Technique/*methods Using modified nucleotides and selecting for slow off-rates in the SELEX procedure, we have evolved a special class of aptamers, called SOMAmers (slow off-rate modified aptamers), which bind tightly and specifically to proteins in body fluids. We use these in a novel assay that yields 1:1 complexes of the SOMAmers with their cognate proteins in body fluids. Measuring the SOMAmer concentrations of the resultant complexes reflects the concentration of the proteins in the fluids. This is simply done by hybridization to complementary sequences on solid supports, but it can also be done by any other DNA quantification technology (including NexGen sequencing). We use measurements of over proteins in under 100 muL of serum or plasma to answer important medical questions, two of which are reviewed here. A number of bioinformatics methods have guided our discoveries, including principal component analysis. We use various methods to evaluate sample handling procedures in our clinical samples and can identify many parameters that corrupt proteomics analysis. Brody, Edward Gold, Larry Mehan, Mike Ostroff, Rachel Rohloff, John Walker, Jeff Zichi, Dom eng Netherlands J Mol Biol. Oct 5;422(5):595-606. doi: 10./j.jmb..06.021. Epub Jun 19.I SomaScan 06/23/ Lourdusamy A, et al. Identification of cis-regulatory variation influencing protein abundance levels in human plasma Hum Mol Genet 21 16 -26 https://www.doi.org/10./hmg/dds186 22,595,970 Aged Aged, 80 and over Aptamers, Nucleotide Blood Proteins/*genetics Female Genetic Predisposition to Disease Genome-Wide Association Study Humans Male Middle Aged *Polymorphism, Single Nucleotide Proteomics/methods Quantitative Trait Loci *Regulatory Sequences, Nucleic Acid Proteins are central to almost all cellular processes, and dysregulation of expression and function is associated with a range of disorders. A number of studies in human have recently shown that genetic factors significantly contribute gene expression variation. In contrast, very little is known about the genetic basis of variation in protein abundance in man. Here, we assayed the abundance levels of proteins in plasma from 96 elderly Europeans using a new aptamer-based proteomic technology and performed genome-wide local (cis-) regulatory association analysis to identify protein quantitative trait loci (pQTL). We detected robust cis-associations for 60 proteins at a false discovery rate of 5%. The most highly significant single nucleotide polymorphism detected was rs (false discovery rate, 2.5 x 10(-12)), mapped within the gene coding sequence of Tenascin C (TNC). Importantly, we identified evidence of cis-regulatory variation for 20 previously disease-associated genes encoding protein, including variants with strong evidence of disease association show significant association with protein abundance levels. These results demonstrate that common genetic variants contribute to the differences in protein abundance levels in human plasma. Identification of pQTLs will significantly enhance our ability to discover and comprehend the biological and functional consequences of loci identified from genome-wide association study of complex traits. This is the first large-scale genetic association study of proteins in plasma measured using a novel, highly multiplexed slow off-rate modified aptamer (SOMAmer) proteomic platform. Lourdusamy, Anbarasu Newhouse, Stephan Lunnon, Katie Proitsi, Petra Powell, John Hodges, Angela Nelson, Sally K Stewart, Alex Williams, Stephen Kloszewska, Iwona Mecocci, Patrizia Soininen, Hilkka Tsolaki, Magda Vellas, Bruno Lovestone, Simon Dobson, Richard eng K01 AG/AG/NIA NIH HHS/ P30 AG/AG/NIA NIH HHS/ U01 AG/AG/NIA NIH HHS/ U19 AG/AG/NIA NIH HHS/ Research Support, Non-U.S. Gov't England Hum Mol Genet. Aug 15;21(16):-26. doi: 10./hmg/dds186. Epub May 16.I SomaScan 05/19/ Mehan MR, et al. Protein signature of lung cancer tissues PLoS One 7 4 e https://www.doi.org/10./journal.pone. 22,509,397 Aged Apoptosis/genetics Biomarkers, Tumor/blood/genetics/metabolism Carcinoma, Non-Small-Cell Lung/blood/genetics/*metabolism Female *Gene Expression Regulation, Neoplastic Humans Inflammation/genetics Lung Neoplasms/blood/genetics/*metabolism Male Middle Aged Neoplasm Invasiveness/genetics Neoplasm Metastasis Neovascularization, Pathologic/genetics Proteome/*analysis Lung cancer remains the most common cause of cancer-related mortality. We applied a highly multiplexed proteomic technology (SOMAscan) to compare protein expression signatures of non small-cell lung cancer (NSCLC) tissues with healthy adjacent and distant tissues from surgical resections. In this first report of SOMAscan applied to tissues, we highlight 36 proteins that exhibit the largest expression differences between matched tumor and non-tumor tissues. The concentrations of twenty proteins increased and sixteen decreased in tumor tissue, thirteen of which are novel for NSCLC. NSCLC tissue biomarkers identified here overlap with a core set identified in a large serum-based NSCLC study with SOMAscan. We show that large-scale comparative analysis of protein expression can be used to develop novel histochemical probes. As expected, relative differences in protein expression are greater in tissues than in serum. The combined results from tissue and serum present the most extensive view to date of the complex changes in NSCLC protein expression and provide important implications for diagnosis and treatment. Mehan, Michael R Ayers, Deborah Thirstrup, Derek Xiong, Wei Ostroff, Rachel M Brody, Edward N Walker, Jeffrey J Gold, Larry Jarvis, Thale C Janjic, Nebojsa Baird, Geoffrey S Wilcox, Sheri K eng PLoS One. ;7(4):e. doi: 10./journal.pone.. Epub Apr 11.I SomaScan 04/18/ Gold L, et al. Advances in human proteomics at high scale with the SOMAscan proteomics platform N Biotechnol 29 5 543-9 https://www.doi.org/10./j.nbt..11.016 22,155,539 Biomarkers/metabolism DNA/*metabolism Humans Proteins/metabolism Proteomics/*instrumentation/methods/*trends In , while still working at NeXstar Pharmaceuticals, several of us made a proteomic bet. We thought then, and continue to think, that proteomics offers a chance to identify disease-specific biomarkers and improve healthcare. However, interrogating proteins turned out to be a much harder problem than interrogating nucleic acids. Consequently, the 'omics' revolution has been fueled largely by genomics. High-scale proteomics promises to transform medicine with personalized diagnostics, prevention, and treatment. We have now reached into the human proteome to quantify more than proteins in any human matrix - serum, plasma, CSF, BAL, and also tissue extracts - with our new SOMAmer-based proteomics platform. The surprising and pleasant news is that we have made unbiased protein biomarker discovery a routine and fast exercise. The downstream implications of the platform are substantial. Gold, Larry Walker, Jeffrey J Wilcox, Sheri K Williams, Stephen eng Review Netherlands N Biotechnol. Jun 15;29(5):543-9. doi: 10./j.nbt..11.016. Epub Dec 7.I SomaScan 12/14/ Baird GS, et al. Age-dependent changes in the cerebrospinal fluid proteome by slow off-rate modified aptamer array Am J Pathol 180 2 446-56 https://www.doi.org/10./j.ajpath..10.024 22,122,984 Adult Aged Aged, 80 and over Aging/genetics/*metabolism Aptamers, Nucleotide/*metabolism Biomarkers/cerebrospinal fluid Cerebrospinal Fluid Proteins/*analysis Female Humans Male Middle Aged Protein Array Analysis/*methods Proteome/genetics/*metabolism Young Adult An important precondition for the successful development of diagnostic assays of cerebrospinal fluid (CSF) biomarkers of age-related neurodegenerative diseases is an understanding of the dynamic nature of the CSF proteome during the normal aging process. In this study, a novel proteomic technology was used to quantify hundreds of proteins simultaneously in the CSF from 90 cognitively normal adults 21 to 85 years of age. SomaLogic's highly multiplexed proteomic platform can measure more than 800 proteins simultaneously from small volumes of biological fluids using novel slow off-rate modified aptamer (SOMAmer) protein affinity reagents with sensitivity, specificity, and dynamic ranges that meet or exceed those of enzyme-linked immunosorbent assays. In the first application of this technology to CSF, we detected 248 proteins that possessed signals greater than twofold over background. Several novel correlations between detected protein concentrations and age were discovered that indicate that both inflammation and response to injury in the central nervous system may increase with age. Applying this powerful proteomic approach to CSF provides potential new insight into the aging of the human central nervous system that may have utility in discovering new disease-related changes in the CSF proteome. Baird, Geoffrey S Nelson, Sally K Keeney, Tracy R Stewart, Alex Williams, Stephen Kraemer, Stephan Peskind, Elaine R Montine, Thomas J eng P50 AG/AG/NIA NIH HHS/ AG/AG/NIA NIH HHS/ Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Am J Pathol. Feb;180(2):446-56. doi: 10./j.ajpath..10.024. Epub Nov 26.I SomaScan 11/30/ Gold L, et al. Aptamers and the RNA world, past and present Cold Spring Harb Perspect Biol 4 3 https://www.doi.org/10./cshperspect.a 21,441,582 Aptamers, Nucleotide/*chemistry Biomarkers/blood/chemistry History, 20th Century Humans Proteomics/methods RNA/*chemistry/physiology SELEX Aptamer Technique/*history Aptamers and the SELEX process were discovered over two decades ago. These discoveries have spawned a productive academic and commercial industry. The collective results provide insights into biology, past and present, through an in vitro evolutionary exploration of the nature of nucleic acids and their potential roles in ancient life. Aptamers have helped usher in an RNA renaissance. Here we explore some of the evolution of the aptamer field and the insights it has provided for conceptualizing an RNA world, from its nascence to our current endeavor employing aptamers in human proteomics to discover biomarkers of health and disease. Gold, Larry Janjic, Nebojsa Jarvis, Thale Schneider, Dan Walker, Jeffrey J Wilcox, Sheri K Zichi, Dom eng Historical Article Review Cold Spring Harb Perspect Biol. Mar 1;4(3):a. doi: 10./cshperspect.a.I SomaScan 03/29/ Kraemer S, et al. From SOMAmer-based biomarker discovery to diagnostic and clinical applications: a SOMAmer-based, streamlined multiplex proteomic assay PLoS One 6 10 e https://www.doi.org/10./journal.pone. 22,022,604 Automation Biological Assay/*methods Biomarkers/*analysis Case-Control Studies *Diagnostic Techniques and Procedures Humans Limit of Detection Nucleic Acids/metabolism Oligonucleotides/chemistry/*metabolism Proteomics/*methods Reproducibility of Results Titrimetry Recently, we reported a SOMAmer-based, highly multiplexed assay for the purpose of biomarker identification. To enable seamless transition from highly multiplexed biomarker discovery assays to a format suitable and convenient for diagnostic and life-science applications, we developed a streamlined, plate-based version of the assay. The plate-based version of the assay is robust, sensitive (sub-picomolar), rapid, can be highly multiplexed (upwards of 60 analytes), and fully automated. We demonstrate that quantification by microarray-based hybridization, Luminex bead-based methods, and qPCR are each compatible with our platform, further expanding the breadth of proteomic applications for a wide user community. Kraemer, Stephan Vaught, Jonathan D Bock, Christopher Gold, Larry Katilius, Evaldas Keeney, Tracy R Kim, Nancy Saccomano, Nicholas A Wilcox, Sheri K Zichi, Dom Sanders, Glenn M eng Research Support, Non-U.S. Gov't PLoS One. ;6(10):e. doi: 10./journal.pone.. Epub Oct 17.I SomaScan 10/25/ Gupta S, et al. Rapid histochemistry using slow off-rate modified aptamers with anionic competition Appl Immunohistochem Mol Morphol 19 3 273-8 https://www.doi.org/10./PAI.0b013ec29 21,217,521 Aptamers, Peptide/chemistry/*metabolism Breast Neoplasms/*diagnosis/metabolism/pathology Carcinoma/*diagnosis/metabolism/pathology Epidermal Growth Factor/metabolism Female Fluorescent Dyes/chemistry/*metabolism Humans *Molecular Diagnostic Techniques Protein Binding Sensitivity and Specificity Immunohistochemistry is used in both research and clinical settings to identify proteins in tissue samples. Despite the power and versatility of immunohistochemistry, limitations are imposed by the slow diffusion of antibodies through tissue and the need for secondary staining or signal amplification. Aptamers can circumvent these limitations, but their application has been hindered by nonspecific binding to cellular components, particularly in the nucleus. Here we describe unique slow off-rate modified aptamers that facilitate rapid and selective binding to target proteins in tissue. Specifically, we have developed a fluorescent aptamer that binds to the human epidermal growth factor receptor 2 (HER2) in breast carcinomas quickly and specifically, and we have shown that the slow off-rate of the aptamer from the HER2 protein contributes to its selectivity. These findings open the door to aptamer histochemistry applications in both research and clinical settings, including intraoperative diagnostics in which speed and accuracy are paramount. Gupta, Shashi Thirstrup, Derek Jarvis, Thale C Schneider, Daniel J Wilcox, Sheri K Carter, Jeff Zhang, Chi Gelinas, Amy Weiss, Allison Janjic, Nebojsa Baird, Geoffrey S eng Research Support, Non-U.S. Gov't Appl Immunohistochem Mol Morphol. May;19(3):273-8. doi: 10./PAI.0b013ec29.I SomaScan 01/11/ Ostroff RM, et al. Unlocking biomarker discovery: large scale application of aptamer proteomic technology for early detection of lung cancer PLoS One 5 12 e https://www.doi.org/10./journal.pone. 21,170,350 Algorithms Autoantibodies/chemistry Biomarkers/*metabolism Biomarkers, Tumor/*metabolism Carcinoma, Non-Small-Cell Lung/*metabolism Case-Control Studies Cohort Studies Early Detection of Cancer/*methods Humans Lung Neoplasms/*metabolism Mass Spectrometry/methods Models, Statistical Proteomics/*methods Sensitivity and Specificity Smoking/adverse effects BACKGROUND: Lung cancer is the leading cause of cancer deaths worldwide. New diagnostics are needed to detect early stage lung cancer because it may be cured with surgery. However, most cases are diagnosed too late for curative surgery. Here we present a comprehensive clinical biomarker study of lung cancer and the first large-scale clinical application of a new aptamer-based proteomic technology to discover blood protein biomarkers in disease. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a multi-center case-control study in archived serum samples from 1,326 subjects from four independent studies of non-small cell lung cancer (NSCLC) in long-term tobacco-exposed populations. Sera were collected and processed under uniform protocols. Case sera were collected from 291 patients within 8 weeks of the first biopsy-proven lung cancer and prior to tumor removal by surgery. Control sera were collected from 1,035 asymptomatic study participants with >/= 10 pack-years of cigarette smoking. We measured 813 proteins in each sample with a new aptamer-based proteomic technology, identified 44 candidate biomarkers, and developed a 12-protein panel (cadherin-1, CD30 ligand, endostatin, HSP90alpha, LRIG3, MIP-4, pleiotrophin, PRKCI, RGM-C, SCF-sR, sL-selectin, and YES) that discriminates NSCLC from controls with 91% sensitivity and 84% specificity in cross-validated training and 89% sensitivity and 83% specificity in a separate verification set, with similar performance for early and late stage NSCLC. CONCLUSIONS/SIGNIFICANCE: This study is a significant advance in clinical proteomics in an area of high unmet clinical need. Our analysis exceeds the breadth and dynamic range of proteome interrogated of previously published clinical studies of broad serum proteome profiling platforms including mass spectrometry, antibody arrays, and autoantibody arrays. The sensitivity and specificity of our 12-biomarker panel improves upon published protein and gene expression panels. Separate verification of classifier performance provides evidence against over-fitting and is encouraging for the next development phase, independent validation. This careful study provides a solid foundation to develop tests sorely needed to identify early stage lung cancer. Ostroff, Rachel M Bigbee, William L Franklin, Wilbur Gold, Larry Mehan, Mike Miller, York E Pass, Harvey I Rom, William N Siegfried, Jill M Stewart, Alex Walker, Jeffrey J Weissfeld, Joel L Williams, Stephen Zichi, Dom Brody, Edward N eng U01 CA/CA/NCI NIH HHS/ P50 CA/CA/NCI NIH HHS/ P50-CA/CA/NCI NIH HHS/ P50 CA/CA/NCI NIH HHS/ 5P30CA/CA/NCI NIH HHS/ U01 CA-10/CA/NCI NIH HHS/ U01-CA/CA/NCI NIH HHS/ U01 CA/CA/NCI NIH HHS/ 5U01CA/CA/NCI NIH HHS/ P30 CA/CA/NCI NIH HHS/ Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't PLoS One. Dec 7;5(12):e. doi: 10./journal.pone..I SomaScan 12/21/ Gold L, et al. Aptamer-based multiplexed proteomic technology for biomarker discovery PLoS One 5 12 e https://www.doi.org/10./journal.pone. 21,165,148 Aged *Aptamers, Nucleotide Biomarkers/*metabolism Evidence-Based Medicine Female Gene Library Genetic Techniques Glomerular Filtration Rate Humans Kidney Failure, Chronic/metabolism Kinetics Male Mass Spectrometry/methods Middle Aged Nucleic Acid Hybridization Oligonucleotide Array Sequence Analysis Proteome Proteomics/*methods Reproducibility of Results BACKGROUND: The interrogation of proteomes (proteomics") in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology and medicine. METHODOLOGY/PRINCIPAL FINDINGS: We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 microL of serum or plasma). Our current assay measures 813 proteins with low limits of detection (1 pM median), 7 logs of overall dynamic range (~100 fM-1 microM), and 5% median coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding signature of DNA aptamer concentrations, which is quantified on a DNA microarray. Our assay takes advantage of the dual nature of aptamers as both folded protein-binding entities with defined shapes and unique nucleotide sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to rapidly discover unique protein signatures characteristic of various disease states. CONCLUSIONS/SIGNIFICANCE: We describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine." Gold, Larry Ayers, Deborah Bertino, Jennifer Bock, Christopher Bock, Ashley Brody, Edward N Carter, Jeff Dalby, Andrew B Eaton, Bruce E Fitzwater, Tim Flather, Dylan Forbes, Ashley Foreman, Trudi Fowler, Cate Gawande, Bharat Goss, Meredith Gunn, Magda Gupta, Shashi Halladay, Dennis Heil, Jim Heilig, Joe Hicke, Brian Husar, Gregory Janjic, Nebojsa Jarvis, Thale Jennings, Susan Katilius, Evaldas Keeney, Tracy R Kim, Nancy Koch, Tad H Kraemer, Stephan Kroiss, Luke Le, Ngan Levine, Daniel Lindsey, Wes Lollo, Bridget Mayfield, Wes Mehan, Mike Mehler, Robert Nelson, Sally K Nelson, Michele Nieuwlandt, Dan Nikrad, Malti Ochsner, Urs Ostroff, Rachel M Otis, Matt Parker, Thomas Pietrasiewicz, Steve Resnicow, Daniel I Rohloff, John Sanders, Glenn Sattin, Sarah Schneider, Daniel Singer, Britta Stanton, Martin Sterkel, Alana Stewart, Alex Stratford, Suzanne Vaught, Jonathan D Vrkljan, Mike Walker, Jeffrey J Watrobka, Mike Waugh, Sheela Weiss, Allison Wilcox, Sheri K Wolfson, Alexey Wolk, Steven K Zhang, Chi Zichi, Dom eng Research Support, Non-U.S. Gov't PLoS One. Dec 7;5(12):e. doi: 10./journal.pone..I SomaScan 12/18/ Brody EN, et al. High-content affinity-based proteomics: unlocking protein biomarker discovery Expert Rev Mol Diagn 10 8 -22 https://www.doi.org/10./erm.10.89 21,080,818 *Aptamers, Nucleotide Biomarkers/*analysis/*chemistry Enzyme-Linked Immunosorbent Assay/methods Genetic Variation Humans Mass Spectrometry Molecular Diagnostic Techniques Proteins/*analysis/chemistry *Proteomics SELEX Aptamer Technique Single protein biomarkers measured with antibody-based affinity assays are the basis of molecular diagnostics in clinical practice today. There is great hope in discovering new protein biomarkers and combinations of protein biomarkers for advancing medicine through monitoring health, diagnosing disease, guiding treatment, and developing new therapeutics. The goal of high-content proteomics is to unlock protein biomarker discovery by measuring many (thousands) or all ( approximately 23,000) proteins in the human proteome in an unbiased, data-driven approach. High-content proteomics has proven technically difficult due to the diversity of proteins, the complexity of relevant biological samples, such as blood and tissue, and large concentration ranges (in the order of 10(12) in blood). Mass spectrometry and affinity methods based on antibodies have dominated approaches to high-content proteomics. For technical reasons, neither has achieved adequate simultaneous performance and high-content. Here we review antibody-based protein measurement, multiplexed antibody-based protein measurement, and limitations of antibodies for high-content proteomics due to their inherent cross-reactivity. Finally, we review a new affinity-based proteomic technology developed from the ground up to solve the problem of high content with high sensitivity and specificity. Based on a new generation of slow off-rate modified aptamers (SOMAmers), this technology is unlocking biomarker discovery. Brody, Edward N Gold, Larry Lawn, Richard M Walker, Jeffrey J Zichi, Dom eng Research Support, Non-U.S. Gov't Review England Expert Rev Mol Diagn. Nov;10(8):-22. doi: 10./erm.10.89.I SomaScan 11/18/ Vaught JD, et al. Expanding the chemistry of DNA for in vitro selection J Am Chem Soc 132 12 -51 https://www.doi.org/10./jag 20,201,573 Aptamers, Nucleotide/*chemistry/genetics/metabolism Base Sequence Gene Library Humans Molecular Sequence Data Molecular Structure Polymerase Chain Reaction Tumor Necrosis Factor Receptor Superfamily, Member 9/*chemistry/genetics/metabolism Six new 5-position modified dUTP derivatives connected by a unique amide linkage were synthesized and tested for compatibility with the enzymatic steps of in vitro selection. Six commercially available DNA polymerases were tested for their ability to efficiently incorporate each of these dUTP derivatives during PCR. It was not possible to perform PCR under standard conditions using any of the modified dUTP derivatives studied. In contrast, primer extension reactions of random templates, as well as defined sequence templates, were successful. KOD XL and D. Vent DNA polymerases were found to be the most efficient at synthesizing full-length primer extension product, with all of the dUTP derivatives tested giving yields similar to those obtained with TTP. Several of these modified dUTPs were then used in an in vitro selection experiment comparing the use of modified dUTP derivatives with TTP for selecting aptamers to a protein target (necrosis factor receptor superfamily member 9, TNFRSF9) that had previously been found to be refractory to in vitro selection using DNA. Remarkably, selections employing modified DNA libraries resulted in the first successful isolation of DNA aptamers able to bind TNFRSF9 with high affinity. Vaught, Jonathan D Bock, Chris Carter, Jeff Fitzwater, Tim Otis, Matt Schneider, Dan Rolando, Justin Waugh, Sheela Wilcox, Sheri K Eaton, Bruce E eng Research Support, U.S. Gov't, Non-P.H.S. J Am Chem Soc. Mar 31;132(12):-51. doi: 10./jag.I SomaScan 03/06/ Ostroff R, et al. The stability of the circulating human proteome to variations in sample collection and handling procedures measured with an aptamer-based proteomics array J Proteomics 73 3 649-66 https://www.doi.org/10./j.jprot..09.004 19,755,178 Algorithms Aptamers, Peptide/chemistry Blood Coagulation/physiology Blood Preservation/adverse effects/methods Blood Proteins/analysis/*metabolism Blood Specimen Collection/adverse effects/*methods/standards Cluster Analysis Freezing/adverse effects Humans Models, Biological Observer Variation Protein Array Analysis/instrumentation/methods *Protein Stability Proteome/*analysis/*metabolism Proteomics/instrumentation/methods SELEX Aptamer Technique/instrumentation/*methods Time Factors Blood-based protein biomarkers hold great promise to advance medicine with applications that detect and diagnose diseases and aid in their treatment. We are developing such applications with our proteomics technology that combines high-content with low limits of detection. Biomarker discovery relies heavily on archived blood sample collections. Blood is dynamic and changes with different sampling procedures potentially confounding biomarker studies. In order to better understand the effects of sampling procedures on the circulating proteome, we studied three sample collection variables commonly encountered in archived sample sets. These variables included (1) three different sample tube types, PPT plasma, SST serum, and Red Top serum, (2) the time from venipuncture to centrifugation, and (3) the time from centrifugation to freezing. We profiled 498 proteins for each of 240 samples and compared the results by ANOVA. The results found no significant variation in the measurements for most proteins (approximately 99%) when the two sample processing times tested were 2h or less, regardless of sample tube type. Even at the longest timepoints, 20 h, approximately 82% of the proteins, on average for the three collection tube types, showed no significant change. These results are encouraging for proteomic biomarker discovery. Ostroff, Rachel Foreman, Trudi Keeney, Tracy R Stratford, Suzanne Walker, Jeffrey J Zichi, Dom eng Evaluation Study Research Support, Non-U.S. Gov't Netherlands J Proteomics. Jan 3;73(3):649-66. doi: 10./j.jprot..09.004. Epub Sep 13.I SomaScan 09/17/ Zichi D, et al. Proteomics and diagnostics: Let's Get Specific, again Curr Opin Chem Biol 12 1 78-85 https://www.doi.org/10./j.cbpa..01.016 18,275,862 Animals Antibodies/immunology Aptamers, Peptide/metabolism *Diagnosis Humans Protein Array Analysis Proteomics/*methods Sensitivity and Specificity DNA array technology has changed all discussions about proteomics. Whole genome arrays allow unbiased experimentation, and the surprises that flow from those approaches. 'Whole proteome' proteomics is not possible today, and might never be possible unless experiments are guided by careful evaluation of reagent specificity. In this paper we explore some possible ways to increase the content of proteomic analysis. Zichi, Dom Eaton, Bruce Singer, Britta Gold, Larry eng Review England Curr Opin Chem Biol. Feb;12(1):78-85. doi: 10./j.cbpa..01.016. Epub Mar 7.I SomaScan 02/16/ Petach H, et al. Processing of photoaptamer microarrays Methods Mol Biol 264 101-10 https://www.doi.org/10./1--759-9:101 15,020,783 Cross-Linking Reagents/metabolism Endostatins/metabolism Fluorescent Dyes/metabolism *Light Nucleic Acids/*metabolism Protein Array Analysis/instrumentation/*methods Protein Binding Photoaptamers are single-stranded nucleic acids selected for their high affinity to specific proteins of interest. Photoaptamer microarrays capture and quantify proteins from complex samples using a unique protocol that leverages both high-affinity capture with covalent retention of analytes. The initial capture of proteins from solution is similar to the well-known antibody capture, but the secondary binding event" affected by photoaptamers is a covalent crosslink between the photoaptamer capture agent and the protein analyte. The nature of this specific covalent reaction allows a unique microarray processing that is described in detail in this chapter." Petach, Helen Ostroff, Rachel Greef, Chad Husar, Gregory M eng Methods Mol Biol. ;264:101-10. doi: 10./1--759-9:101.I SomaScan 03/17/ Smith D, et al. Sensitivity and specificity of photoaptamer probes Mol Cell Proteomics 2 1 8-Nov https://www.doi.org/10./mcp.m-mcp200 12,601,078 Bromodeoxyuridine/*pharmacology Cross-Linking Reagents/*pharmacology Escherichia coli/metabolism HIV Envelope Protein gp120/chemistry Kinetics Oligonucleotide Array Sequence Analysis Peptides/*chemistry Protein Array Analysis Protein Binding Proteomics/methods Sensitivity and Specificity The potential of photoaptamers as proteomic probes was investigated. Photoaptamers are defined as aptamers that bear photocross-linking functionality, in this report, 5-bromo-2'-deoxyuridine. A key question regarding the use of photoaptamer probes is the specificity of the cross-linking reaction. The specificity of three photoaptamers was explored by comparing their reactions with target proteins and non-target proteins. The range of target/non-target specificity varies from 100- to >10(6)-fold with most values >10(4)-fold. The contributions of the initial binding step and the photocross-linking step were evaluated for each reaction. Photocross-linking never degraded specificity and significantly increased aptamer specificity in some cases. The application of photoaptamer technology to proteomics was investigated in microarray format. Immobilized anti-human immunodeficiency virus-gp120 aptamer was able to detect subnanomolar concentrations of target protein in 5% human serum. The levels of sensitivity and specificity displayed by photoaptamers, combined with other advantageous properties of aptamers, should facilitate development of protein chip technology. Smith, Drew Collins, Brian D Heil, James Koch, Tad H eng Research Support, Non-U.S. Gov't Mol Cell Proteomics. Jan;2(1):11-8. doi: 10./mcp.m-mcp200.I SomaScan 02/26/ Gold L, et al. One, two, infinity: genomes filled with aptamers Chem Biol 9 12 -64 https://www.doi.org/10./s-(02)-7 12,498,875 Evolution, Molecular Gene Expression Regulation/genetics Genome Oligonucleotides/*genetics/therapeutic use RNA/chemistry/genetics Gold, Larry Brody, Ed Heilig, Joe Singer, Britta eng Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Chem Biol. Dec;9(12):-64. doi: 10./s-(02)-7.I SomaScan 12/25/ Petach H, et al. Dimensionality is the issue: use of photoaptamers in protein microarrays Curr Opin Biotechnol 13 4 309-14 https://www.doi.org/10./s-(02)-4 12,323,351 Electrophoresis, Gel, Two-Dimensional/*methods Enzyme-Linked Immunosorbent Assay/*methods Indicators and Reagents/chemistry Ligands Molecular Probes Photochemistry/*methods Protein Array Analysis/*methods/trends Proteins/*analysis/*chemistry Proteomics/methods Sensitivity and Specificity The development of high-density arrays for proteomics has become a goal of SomaLogic, many other companies, and a wide variety of academic entities. Unfortunately, the word proteomics has come to mean virtually everything. We define proteomics as being derived from arrays of analyte-specific reagents (ASRs) used to measure (something about) proteins. As the density of the ASRs on a chip increases toward the number of proteins in an organism, the concept of proteomics moves toward comprehensive proteomics. At issue then, is what constitutes an ASR, and what differences between them lead toward more or less biological information from a high-density panel of ASRs. Petach, Helen Gold, Larry eng Review England Curr Opin Biotechnol. Aug;13(4):309-14. doi: 10./s-(02)-4.I SomaScan 09/27/ Zimmermann GR, et al. Interlocking structural motifs mediate molecular discrimination by a theophylline-binding RNA Nat Struct Biol 4 8 644-9 https://www.doi.org/10./nsb-644 9,253,414 Bronchodilator Agents/*chemistry Caffeine/chemistry Cytosine/chemistry Magnetic Resonance Spectroscopy Models, Molecular Molecular Sequence Data *Nucleic Acid Conformation RNA/*chemistry Sensitivity and Specificity Theophylline/*chemistry To visualize the interplay of RNA structural interactions in a ligand binding site, we have determined the solution structure of a high affinity RNA-theophylline complex using NMR spectroscopy. The structure provides insight into the ability of this in vitro selected RNA to discriminate theophylline from the structurally similar molecule caffeine. Numerous RNA structural motifs combine to form a well-ordered binding pocket where an intricate network of hydrogen bonds and stacking interactions lock the theophylline into the complex. Two internal loops interact to form the binding site which consists of a sandwich of three base triples. The complex also contains novel base-zipper and 1-3-2 stacking motifs, in addition to an adenosine platform and a reversed sugar. An important feature of the RNA is that many of the conserved core residues participate in multiple overlapping tertiary interactions. This complex illustrates how interlocking structural motifs can be assembled into a highly specific ligand-binding site that possesses high levels of affinity and molecular discrimination. Zimmermann, G R Jenison, R D Wick, C L Simorre, J P Pardi, A eng Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Nat Struct Biol. Aug;4(8):644-9. doi: 10./nsb-644.I SomaScan 08/01/ Eaton BE, et al. Let's get specific: the relationship between specificity and affinity Chem Biol 2 10 633-8 https://www.doi.org/10./-(95)-3 9,383,468 Animals Drug Design Humans Protein Binding Receptors, Drug/*chemistry Surface Properties The factors that lead to high-affinity binding are a good fit between the surfaces of the two molecules in their ground state and charge complementarity. Exactly the same factors give high specificity for a target. We argue that selection for high-affinity binding automatically leads to highly specific binding. This principle can be used to simplify screening approaches aimed at generating useful drugs. Eaton, B E Gold, L Zichi, D A eng Review Chem Biol. Oct;2(10):633-8. doi: 10./-(95)-3.I SomaScan 10/01/