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Record W2951428751 · doi:10.1371/journal.pone.0181585

Progress towards a public chemogenomic set for protein kinases and a call for contributions

2017· article· en· W2951428751 on OpenAlex
David H. Drewry, Carrow I. Wells, David Andrews, Richard Angell, Hassan Al‐Ali, Alison D. Axtman, Stephen J. Capuzzi, Jonathan M. Elkins, Peter Ettmayer, Mathias Frederiksen, O. Gileadi, Nathanael S. Gray, Alice Hooper, Stefan Knapp, Stefan Laufer, Ulrich Luecking, Michel Michaelides, Susanne Müller, Eugene Muratov, R. Aldrin Denny, Kumar Singh Saikatendu, Daniel K. Treiber, William J. Zuercher, Timothy M. Willson

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenuePLoS ONE · 2017
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtein Degradation and Inhibitors
Canadian institutionsnot available
FundersEshelman Institute for Innovation, University of North Carolina at Chapel HillNational Institute of Diabetes and Digestive and Kidney DiseasesMinistero dello Sviluppo EconomicoFundação de Amparo à Pesquisa do Estado de São PauloNational Institute of Mental HealthEuropean Federation of Pharmaceutical Industries and AssociationsNovartis PharmaWellcome TrustOntario Ministry of Economic Development and InnovationGenome CanadaPfizer
KeywordsKinomeKinaseDrug discoveryComputational biologyFunction (biology)Complement (music)Set (abstract data type)BiologyBioinformaticsComputer scienceCell biologyBiochemistryGene

Abstract

fetched live from OpenAlex

Protein kinases are highly tractable targets for drug discovery. However, the biological function and therapeutic potential of the majority of the 500+ human protein kinases remains unknown. We have developed physical and virtual collections of small molecule inhibitors, which we call chemogenomic sets, that are designed to inhibit the catalytic function of almost half the human protein kinases. In this manuscript we share our progress towards generation of a comprehensive kinase chemogenomic set (KCGS), release kinome profiling data of a large inhibitor set (Published Kinase Inhibitor Set 2 (PKIS2)), and outline a process through which the community can openly collaborate to create a KCGS that probes the full complement of human protein kinases.

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.

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: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.019
Threshold uncertainty score0.362

Codex and Gemma teacher scores by category

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

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 head0.058
GPT teacher head0.290
Teacher spread0.232 · 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