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Record W4307482819 · doi:10.1101/2022.10.27.514070

A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients

2022· preprint· en· W4307482819 on OpenAlex
Yered Pita-Juárez, Dimitra Karagkouni, Nikolaos Kalavros, Johannes C. Melms, Sebastian Niezen, Toni Delorey, Adam L. Essene, Olga R. Brook, Deepti Pant, Disha Skelton-Badlani, Pourya Naderi Yeganeh, Pinzhu Huang, Liuliu Pan, Tyler Hether, Tallulah Andrews, Carly G.K. Ziegler, Jason Reeves, Andriy Myloserdnyy, Rachel Chen, Andy Nam, Stefan Phelan, Yan Liang, Amit Dipak Amin, Jana Biermann, Hanina Hibshoosh, Molly Veregge, Zachary Kramer, Christopher Jacobs, Yusuf Yalcin, Devan Phillips, Michal Slyper, Ayshwarya Subramanian, Orr Ashenberg, Zohar Bloom‐Ackermann, Victoria M. Tran, James Gomez, Alexander Sturm, Shuting Zhang, Stephen J. Fleming, Sarah Warren, Joseph Beechem, Deborah T. Hung, Mehrtash Babadi, Robert F. Padera, Sonya A. MacParland, Gary D. Bader, Nasser Imad, Isaac H. Solomon, Eric Miller, Stefan Riedel, Caroline Porter, Alexandra–Chloé Villani, Linus Tsai, Gyöngyi Szabó, Jonathan L. Hecht, Orit Rozenblatt–Rosen, Alex K. Shalek, Benjamin Izar, Aviv Regev, Yury Popov, Z. Gordon Jiang, Ioannis S. Vlachos

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2022
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicSingle-cell and spatial transcriptomics
Canadian institutionsUniversity of TorontoCanada Research ChairsUniversity Health Network
FundersIrving Medical Center, Columbia UniversityNational Institutes of HealthHamilton Health Sciences FoundationManton FoundationHoward Hughes Medical InstituteMassachusetts Life Sciences CenterChan Zuckerberg InitiativeNational Cancer InstituteBrigham and Women's HospitalRagon Institute of MGH, MIT and HarvardBeth Israel Deaconess Medical CenterU.S. Department of DefenseBill and Melinda Gates FoundationMassachusetts General HospitalBurroughs Wellcome Fund
KeywordsTranscriptomePhenotypeLiver injuryBiologyProgenitor cellPathologyContext (archaeology)Cell biologyNecroptosisLungGene expression profilingStem cellGene expressionMedicineProgrammed cell deathGeneInternal medicineEndocrinologyGenetics

Abstract

fetched live from OpenAlex

The molecular underpinnings of organ dysfunction in acute COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we performed single-nucleus RNA-seq and spatial transcriptomic profiling of livers from 17 COVID-19 decedents. We identified hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells. Integrated analysis and comparisons with healthy controls revealed extensive changes in the cellular composition and expression states in COVID-19 liver, reflecting hepatocellular injury, ductular reaction, pathologic vascular expansion, and fibrogenesis. We also observed Kupffer cell proliferation and erythrocyte progenitors for the first time in a human liver single-cell atlas, resembling similar responses in liver injury in mice and in sepsis, respectively. Despite the absence of a clinical acute liver injury phenotype, endothelial cell composition was dramatically impacted in COVID-19, concomitantly with extensive alterations and profibrogenic activation of reactive cholangiocytes and mesenchymal cells. Our atlas provides novel insights into liver physiology and pathology in COVID-19 and forms a foundational resource for its investigation and understanding.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.566
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.023
GPT teacher head0.218
Teacher spread0.195 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it