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Record W3091081431 · doi:10.1016/j.isci.2020.101697

Integrative Transcriptome Analyses Empower the Anti-COVID-19 Drug Arsenal

2020· article· en· W3091081431 on OpenAlexafffund
Nehmé El-Hachem, Edward Eid, Georges Nemer, Ghassan Dbaibo, Ossama Abbas, Nelly Rubeiz, Salah Zeineldine, Ghassan M. Matar, Jean‐Pierre Bikorimana, Riam Shammaa, Benjamin Haibe‐Kains, Mazen Kurban, Moutih Rafei

Bibliographic record

VenueiScience · 2020
Typearticle
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsMcGill UniversityPrincess Margaret Cancer CentreVector InstituteIntelliView Technologies (Canada)Ontario Institute for Cancer ResearchUniversity Health NetworkUniversity of TorontoUniversité de MontréalCentre Hospitalier Universitaire Sainte-Justine
FundersNatural Sciences and Engineering Research Council of CanadaCancer Research Society
KeywordsTranscriptomePandemicCoronavirus disease 2019 (COVID-19)DrugPopulationCoronavirusClinical trialMedicineOutbreakBiologyBioinformaticsComputational biologyPharmacologyDiseaseVirologyInfectious disease (medical specialty)GeneticsInternal medicineGeneEnvironmental health

Abstract

fetched live from OpenAlex

The beginning of the 21st century has been marked by three distinct waves of zoonotic coronavirus outbreaks into the human population. The COVID-19 (coronavirus disease 2019) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and emerged as a global threat endangering the livelihoods of millions worldwide. Currently, and despite collaborative efforts, diverse therapeutic strategies from ongoing clinical trials are still debated. To address the need for such an immediate call of action, we leveraged the largest dataset of drug-induced transcriptomic perturbations, public SARS-CoV-2 transcriptomic datasets, and expression profiles from normal lung transcriptomes. Most importantly, our unbiased systems biology approach prioritized more than 50 repurposable drug candidates (e.g., corticosteroids, Janus kinase and Bruton kinase inhibitors). Further clinical investigation of these FDA-approved candidates as monotherapy or in combination with an antiviral regimen (e.g., remdesivir) could lead to promising outcomes in patients with COVID-19.

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)0.000
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
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 score0.604
Threshold uncertainty score0.350

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0010.000
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 head0.125
GPT teacher head0.433
Teacher spread0.308 · 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.

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

Citations16
Published2020
Admission routes2
Has abstractyes

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