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Record W3126821152 · doi:10.1101/2021.02.10.430527

CRISPR perturbations at many coronary artery disease loci impair vascular endothelial cell functions

2021· preprint· en· W3126821152 on OpenAlexafffund
Florian Wünnemann, Thierry Fotsing Tadjo, Mélissa Beaudoin, Simon Lalonde, Ken Sin Lo, Guillaume Lettre

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2021
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCRISPR and Genetic Engineering
Canadian institutionsUniversité de MontréalMontreal Heart Institute
FundersFonds de Recherche du Québec - SantéCanadian Institutes of Health ResearchFondation Institut de Cardiologie de MontréalInstitut de Cardiologie de MontréalHeart and Stroke Foundation of CanadaGénome QuébecCompute Canada
KeywordsBiologyCRISPRPhenotypeGenome-wide association studyGeneCoronary artery diseaseGeneticsFurinEndothelial stem cellNitric oxideCell biologySingle-nucleotide polymorphismInternal medicineGenotypeMedicineIn vitroBiochemistryEnzymeEndocrinology

Abstract

fetched live from OpenAlex

ABSTRACT Genome-wide association studies have identified 161 genetic variants associated with coronary artery disease (CAD), but the causal genes and biological pathways remain unknown at most loci. Here, we used CRISPR knockout, inhibition and activation to target 1998 variants at 83 CAD loci to assess their effect on six vascular endothelial cell phenotypes (E-selectin, ICAM1, VCAM1, nitric oxide, reactive oxygen species, calcium signalling). We identified 42 significant variants located within 26 CAD loci. Detailed characterization of the RNA helicase DHX38 and CRISPR activation at the FURIN/FES, CCDC92/ZNF664 and CNNM2 loci revealed a strong effect on vascular endothelial cell senescence.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

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)0.0030.001

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 head0.007
GPT teacher head0.218
Teacher spread0.211 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
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

Citations5
Published2021
Admission routes2
Has abstractyes

Explore more

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