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Record W4395954697 · doi:10.1101/2024.04.23.590739

Chemical Coverage of the Human Reactome

2024· preprint· en· W4395954697 on OpenAlexafffund
Haejin Angela Kwak, Lihua Liu, Claudia Tredup, Sandra Röhm, Panagiotis Prinos, Jark Böttcher, Matthieu Schapira

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2024
Typepreprint
Languageen
FieldComputer Science
TopicComputational Drug Discovery Methods
Canadian institutionsStructural Genomics ConsortiumCanada Research ChairsUniversity of Toronto
FundersNatural Sciences and Engineering Research Council of CanadaOntario Genomics InstituteEuropean Federation of Pharmaceutical Industries and AssociationsMerck KGaACanadian Institutes of Health ResearchOntario GenomicsGenome CanadaMcGill UniversityGenentechBayerPfizerBristol-Myers Squibb
KeywordsComputer scienceComputational biologyBiology

Abstract

fetched live from OpenAlex

Abstract Chemical probes and chemogenomic compounds are valuable tools to link gene to phenotype, explore human biology and uncover novel targets for precision medicine. A growing federation of scientists is contributing to the mission of Target 2035 – discovering chemical tools for all druggable human proteins by the year 2035. It is expected that these compounds will enable the understanding of the regulation of cellular machineries and biological processes across the compendium of signaling pathways that animate cellular life. Here, we draw a landscape of the current chemical coverage of the human Reactome. We find that even though available chemical probes and chemogenomic compounds are targeting only 3% of the human proteome, they cover 53% of the human Reactome, due to the fact that 46% of human proteins are involved in more than one cellular pathway. As such, existing chemical probes and chemogenomic compounds already represent a versatile toolkit to manipulate a vast portion of human biology. Pathways targeted by existing drugs may be enriched in unknown but valid drug targets and could be prioritized in future Target 2035 efforts.

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)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Methods · Consensus signal: none
Teacher disagreement score0.006
Threshold uncertainty score0.019

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0020.002
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0060.001

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 head0.018
GPT teacher head0.262
Teacher spread0.243 · 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 designSimulation or modeling
Domainnot available
GenreMethods

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

Citations0
Published2024
Admission routes2
Has abstractyes

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