MétaCan
Menu
Back to cohort
Record W4291552122 · doi:10.1038/s41467-022-31999-6

ELF5 is a potential respiratory epithelial cell-specific risk gene for severe COVID-19

2022· article· en· W4291552122 on OpenAlexafffund
Maik Pietzner, Robert Lorenz Chua, Eleanor Wheeler, Katharina Jechow, Julian Willett, Helena Radbruch, Saskia Trump, Bettina Heidecker, Hugo Zeberg, Frank L. Heppner, Roland Eils, Marcus Mall, J. Brent Richards, Leif Erik Sander, Irina Lehmann, Soeren Lukassen, Nicholas J. Wareham, Christian Conrad, Claudia Langenberg

Bibliographic record

VenueNature Communications · 2022
Typearticle
Languageen
FieldMedicine
TopicCOVID-19 Clinical Research Studies
Canadian institutionsMcGill University Health CentreMcGill UniversityMcGill Genome CentreJewish General Hospital
FundersMedical Research CouncilDeutsche ForschungsgemeinschaftCanadian Institutes of Health ResearchNational Institute for Health and Care ResearchUniversity of CambridgeCancer Research UKWellcome Trust
KeywordsPopulationOdds ratioBiologyGeneMedicineSingle-cell analysisImmunologyInternal medicineBioinformaticsCellGenetics

Abstract

fetched live from OpenAlex

Abstract Despite two years of intense global research activity, host genetic factors that predispose to a poorer prognosis of COVID-19 infection remain poorly understood. Here, we prioritise eight robust (e.g., ELF5) or suggestive but unreported (e.g., RAB2A) candidate protein mediators of COVID-19 outcomes by integrating results from the COVID-19 Host Genetics Initiative with population-based plasma proteomics using statistical colocalisation. The transcription factor ELF5 ( ELF5 ) shows robust and directionally consistent associations across different outcome definitions, including a >4-fold higher risk (odds ratio: 4.88; 95%-CI: 2.47–9.63; p-value < 5.0 × 10 −6 ) for severe COVID-19 per 1 s.d. higher genetically predicted plasma ELF5. We show that ELF5 is specifically expressed in epithelial cells of the respiratory system, such as secretory and alveolar type 2 cells, using single-cell RNA sequencing and immunohistochemistry. These cells are also likely targets of SARS-CoV-2 by colocalisation with key host factors, including ACE2 and TMPRSS2 . In summary, large-scale human genetic studies together with gene expression at single-cell resolution highlight ELF5 as a risk gene for severe COVID-19, supporting a role of epithelial cells of the respiratory system in the adverse host response to SARS-CoV-2.

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, Science and technology studies, Research integrity
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: Not applicable
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.856
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.013
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0020.000
Scholarly communication0.0000.000
Open science0.0010.002
Research integrity0.0000.003
Insufficient payload (model declined to judge)0.0010.000

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 head0.077
GPT teacher head0.436
Teacher spread0.359 · 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 designNot applicable
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

Citations35
Published2022
Admission routes2
Has abstractyes

Explore more

Same venueNature CommunicationsSame topicCOVID-19 Clinical Research StudiesFrench-language works237,207