ArticleCell systems2022
Multiomic analysis reveals cell-type-specific molecular determinants of COVID-19 severity.
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Article in Cell systems, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18citing papers in PubMed
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18 citing papers in PubMed, 37 citations in OpenAlex.
- A review on fungal pathogens in the One Health framework: connecting plant, animal, and human health.Archives of microbiology · 2026Review
- Single-cell polygenic risk scores dissect cellular and molecular heterogeneity of complex human diseases.Nature biotechnology · 2026Article
- Recombinant Bacillus subtilis spores expressing SARS-CoV-2 spike protein induced humoral, mucosal, and cellular immunity in mice.Scientific reports · 2025Article
- Dissecting the genetic complexity of myalgic encephalomyelitis/chronic fatigue syndrome via deep learning-powered genome analysis.medRxiv : the preprint server for health sciences · 2025Article
- Longitudinal immune profiling uncovers regulatory T cell signatures associated with the progression of COVID-19.Frontiers in immunology · 2025Article
- Clinical features and predictive nomogram for fatigue sequelae in non-severe patients infected with SARS-CoV-2 Omicron variant in Shanghai, China.Brain, behavior, & immunity - health · 2024Article
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- Influence of Th1 versus Th2 immune bias on viral, pathological, and immunological dynamics in SARS-CoV-2 variant-infected human ACE2 knock-in mice.EBioMedicine · 2024Article
- Associations between immune cell traits and autoimmune thyroid diseases: a bidirectional two-sample mendelian randomization study.Immunogenetics · 2024Article
- Emerging Microorganisms and Infectious Diseases: One Health Approach for Health Shared Vision.Genes · 2024Review
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- A Retrospective Data Audit of Outcome of Moderate and Severe Covid-19 Patients Who Had Received MP and Dex: A Single Center Study.Infection and drug resistance · 2024Article
- From bench to bedside via bytes: Multi-omic immunoprofiling and integration using machine learning and network approaches.Human vaccines & immunotherapeutics · 2023Review
- Multi-Omics Profiling for Health.Molecular & cellular proteomics : MCP · 2023Review
- The natural killer cell-associated rs9916629-C allele is a novel genetic risk factor for fatal COVID-19.Journal of medical virology · 2023Article
- Low expression of EXOSC2 protects against clinical COVID-19 and impedes SARS-CoV-2 replication.Life science alliance · 2023Article
- Machine Learning and COVID-19: Lessons from SARS-CoV-2.Advances in experimental medicine and biology · 2023Article
Corrections and comments
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Authors and funding
20 authors at 9 institutions in 4 countries.
Sai ZhangDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; VA Palo Alto Epidemiology Research and Information Center for Genomics, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA; Center for Genomics and Personalized Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Johnathan Cooper-KnockSheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK.
Annika K WeimerDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Center for Genomics and Personalized Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Minyi ShiDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Center for Genomics and Personalized Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Lina KozhayaThe Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
Derya UnutmazThe Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
Calum HarveySheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK.
Thomas H JulianSheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK.
Simone FuriniMed Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy.
Elisa FrullantiMed Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy; Medical Genetics, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy.
Francesca FavaMed Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy; Medical Genetics, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy; Genetica Medica, Azienda Ospedaliero-Universitaria Senese, 53100 Siena, Italy.
Alessandra RenieriMed Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy; Medical Genetics, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy; Genetica Medica, Azienda Ospedaliero-Universitaria Senese, 53100 Siena, Italy.
Peng GaoDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Center for Genomics and Personalized Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Xiaotao ShenDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Center for Genomics and Personalized Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Ilia Sarah TimpanaroDepartment of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands.
Kevin P KennaDepartment of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands.
J Kenneth BaillieRoslin Institute, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK; Intensive Care Unit, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, UK.
Mark M DavisInstitute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Philip S TsaoVA Palo Alto Epidemiology Research and Information Center for Genomics, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: ptsao@stanford.edu.
Michael P SnyderDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Center for Genomics and Personalized Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: mpsnyder@stanford.edu.
Stanford University · USUniversity of Sheffield · GBAzienda Ospedaliera Universitaria Senese · ITCardiovascular Institute of the South · USJackson Laboratory · USUniversity Medical Center Utrecht · NLUniversity of Siena · ITHoward Hughes Medical Institute · USWestern General Hospital · GB
Funding
Using a tonsil organoid system to probe conditions for the induction of protective antibody and T cell responses to influenza.U19AI057229 · NIAID · STANFORD UNIVERSITY · PI Mark Morris Davis · 2003 to 2026
$88.5MPRODUCTION CENTER FOR MAPPING REGULATORY REGIONS OF THE HUMAN GENOMEUM1HG009442 · NHGRI · STANFORD UNIVERSITY · PI SNYDER, MICHAEL P. · 2017 to 2021
$20.1MStanford Islet Research CoreP30DK116074 · NIDDK · STANFORD UNIVERSITY · PI Seung K Kim · 2017 to 2026
$19.5MThe effects of immune-age on immune-response and the molecular mechanisms which drive itP01AI153559 · NIAID · STANFORD UNIVERSITY · PI DAVIS, MARK MORRIS · 2021 to 2025
$17.8MSignature Protein Profiles to Identify AAAsP50HL083800 · NHLBI · STANFORD UNIVERSITY · PI CONNOLLY, ANDREW J · 2006 to 2010
$13.7MDNA Variants and AAA DiseaseR01HL101388 · NHLBI · STANFORD UNIVERSITY · PI TSAO, PHILIP S · 2010 to 2013
$1.6MMicroRNA Regulation of Nicotine Accelerated AAAsR01HL122939 · NHLBI · PALO ALTO VETERANS INSTIT FOR RESEARCH · PI TSAO, PHILIP S · 2014 to 2017
$1.4MComputational appliance: a supercomputer for modern biomedical researchS10OD023452 · OD · STANFORD UNIVERSITY · PI DATTA, SOMALEE · 2017 to 2017
$600kUltra high throughput sequencer for sustaining and enhancing multi-scale genomic studiesS10OD025212 · OD · STANFORD UNIVERSITY · PI SNYDER, MICHAEL P. · 2018 to 2018
$600kNHGRI NIH HHS UM1 HG009442NHLBI NIH HHS P50 HL083800NHLBI NIH HHS R01 HL101388NHLBI NIH HHS R01 HL122939NIAID NIH HHS P01 AI153559NIAID NIH HHS U19 AI057229NIDDK NIH HHS P30 DK116074NIH HHS S10 OD023452NIH HHS S10 OD025212Wellcome TrustWellcome Trust 216596/Z/19/Z
Abstract
The determinants of severe COVID-19 in healthy adults are poorly understood, which limits the opportunity for early intervention. We present a multiomic analysis using machine learning to characterize the genomic basis of COVID-19 severity. We use single-cell multiome profiling of human lungs to link genetic signals to cell-type-specific functions. We discover >1,000 risk genes across 19 cell types, which account for 77% of the SNP-based heritability for severe disease. Genetic risk is particularly focused within natural killer (NK) cells and T cells, placing the dysfunction of these cells upstream of severe disease. Mendelian randomization and single-cell profiling of human NK cells support the role of NK cells and further localize genetic risk to CD56
Indexed as
COVID-19AdultCD56 AntigenCytokinesGenetic Predisposition to DiseaseHumansKiller Cells, NaturalPolymorphism, Single NucleotideCD56 AntigenCytokinesCOVID-19gene discoverygenome-wide association studyGWASmachine learningMendelian randomizationnetwork analysisNK cellrare variant analysissingle-cell multiomic profiling
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.