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Record W3165277981 · doi:10.1172/jci147834

Rare loss-of-function variants in type I IFN immunity genes are not associated with severe COVID-19

2021· article· en· W3165277981 on OpenAlexaff
Gundula Povysil, Guillaume Butler‐Laporte, Ning Shang, Chen Wang, Atlas Khan, Manal Alaamery, Tomoko Nakanishi, Sirui Zhou, Vincenzo Forgetta, Robert Eveleigh, Mathieu Bourgey, Naveed Aziz, Steven J.M. Jones, Bartha Maria Knoppers, Stephen W. Scherer, Lisa J. Strug, Pierre Lepage, Jiannis Ragoussis, Guillaume Bourque, Jahad Alghamdi, Nora Aljawini, Nour Albes, Hani Al-Afghani, Bader Alghamdi, Mansour Almutairi, Ebrahim Mahmoud, Leen Abu‐Safieh, Hadeel El Bardisy, Fawz S. Al Harthi, Abdulraheem Alshareef, Bandar A. Suliman, Saleh A. Alqahtani, Abdulaziz Almalik, May Alrashed, Salam Massadeh, Vincent Mooser, Mark Lathrop, Fawzy Mohamed, Yaseen M. Arabi, Hamdi Mbarek, Chadi Saad, Wadha Al‐Muftah, Junghyun Jung, Serghei Mangul, Radja Badji, Asma Al Thani, Said I. Ismail, Ali G. Gharavi, Malak Abedalthagafi, J. Brent Richards, David B. Goldstein, Krzysztof Kiryluk

Bibliographic record

VenueJournal of Clinical Investigation · 2021
Typearticle
Languageen
FieldImmunology and Microbiology
Topicinterferon and immune responses
Canadian institutionsOntario GenomicsMcGill Genome CentreMcGill UniversityJewish General Hospital
FundersNational Center for Advancing Translational SciencesNational Institute on Aging
KeywordsBiologyGeneExome sequencingGeneticsPopulationCandidate geneLoss functionCoronavirus disease 2019 (COVID-19)ExomeMutationDiseaseMedicinePhenotypeInternal medicine

Abstract

fetched live from OpenAlex

A recent report found that rare predicted loss-of-function (pLOF) variants across 13 candidate genes in TLR3- and IRF7-dependent type I IFN pathways explain up to 3.5% of severe COVID-19 cases. We performed whole-exome or whole-genome sequencing of 1,864 COVID-19 cases (713 with severe and 1,151 with mild disease) and 15,033 ancestry-matched population controls across 4 independent COVID-19 biobanks. We tested whether rare pLOF variants in these 13 genes were associated with severe COVID-19. We identified only 1 rare pLOF mutation across these genes among 713 cases with severe COVID-19 and observed no enrichment of pLOFs in severe cases compared to population controls or mild COVID-19 cases. We found no evidence of association of rare LOF variants in the 13 candidate genes with severe COVID-19 outcomes.

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.

How this classification was reachedexpand

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)0.002
metaresearch head score (Gemma)0.013
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.176
Threshold uncertainty score0.995

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.013
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
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 head0.107
GPT teacher head0.363
Teacher spread0.255 · 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

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations70
Published2021
Admission routes1
Has abstractyes

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