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Record W4283835519 · doi:10.1038/s41570-022-00363-z

CACHE (Critical Assessment of Computational Hit-finding Experiments): A public–private partnership benchmarking initiative to enable the development of computational methods for hit-finding

2022· review· en· W4283835519 on OpenAlexaff
Suzanne Ackloo, Rima Al‐awar, Rommie E. Amaro, C.H. Arrowsmith, Hatylas Azevedo, Robert A. Batey, Yoshua Bengio, Ulrich A. K. Betz, Cristian Bologa, John D. Chodera, Wendy D. Cornell, Ian Dunham, Gerhard F. Ecker, Kristina Edfeldt, A.M. Edwards, Michael K. Gilson, Cláudia R. Gordijo, Gerhard Heßler, Alexander Hillisch, Anders Hogner, John J. Irwin, Johanna M. Jansen, Daniel Kühn, Andrew R. Leach, Alpha A. Lee, Uta Lessel, Maxwell R. Morgan, John Moult, Ingo Muegge, Tudor I. Oprea, Benjamin Perry, Patrick Riley, Sophie A. L. Rousseaux, Kumar Singh Saikatendu, Vijayaratnam Santhakumar, Matthieu Schapira, Cora Scholten, Matthew H. Todd, Masoud Vedadi, Andrea Volkamer, Timothy M. Willson

Bibliographic record

VenueNature Reviews Chemistry · 2022
Typereview
Languageen
FieldComputer Science
TopicComputational Drug Discovery Methods
Canadian institutionsMila - Quebec Artificial Intelligence InstituteUniversité de MontréalStructural Genomics ConsortiumOntario Institute for Cancer ResearchUniversity of Toronto
FundersNational Center for Advancing Translational SciencesNational Cancer InstituteKarolinska InstitutetNational Institute of General Medical SciencesBayer
KeywordsBenchmarkingComputer scienceCacheIdentification (biology)Computational modelBenchmark (surveying)Drug discoveryData scienceChemical spaceMachine learningArtificial intelligenceBioinformaticsParallel computingBiologyBusiness

Abstract

fetched live from OpenAlex

One aspirational goal of computational chemistry is to predict potent and drug-like binders for any protein, such that only those that bind are synthesized. In this Roadmap, we describe the launch of Critical Assessment of Computational Hit-finding Experiments (CACHE), a public benchmarking project to compare and improve small-molecule hit-finding algorithms through cycles of prediction and experimental testing. Participants will predict small-molecule binders for new and biologically relevant protein targets representing different prediction scenarios. Predicted compounds will be tested rigorously in an experimental hub, and all predicted binders as well as all experimental screening data, including the chemical structures of experimentally tested compounds, will be made publicly available and not subject to any intellectual property restrictions. The ability of a range of computational approaches to find novel binders will be evaluated, compared and openly published. CACHE will launch three new benchmarking exercises every year. The outcomes will be better prediction methods, new small-molecule binders for target proteins of importance for fundamental biology or drug discovery and a major technological step towards achieving the goal of Target 2035, a global initiative to identify pharmacological probes for all human proteins. Critical Assessment of Computational Hit-finding Experiments (CACHE) is a public benchmarking project to compare and improve computational small-molecule hit-finding approaches through cycles of prediction, compound synthesis and experimental testing. By that, CACHE will enable a more efficient and effective approach to hit identification and drug discovery.

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)0.100
metaresearch head score (Gemma)0.111
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: Not applicable
GenreCandidate signal: Review · Consensus signal: none
Teacher disagreement score0.100
Threshold uncertainty score0.529

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.1000.111
Meta-epidemiology (narrow)0.0040.001
Meta-epidemiology (broad)0.0030.003
Bibliometrics0.0040.006
Science and technology studies0.0020.003
Scholarly communication0.0060.007
Open science0.0120.012
Research integrity0.0040.007
Insufficient payload (model declined to judge)0.0150.007

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 head0.285
GPT teacher head0.534
Teacher spread0.249 · 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 designNot applicable
Domainnot available
GenreReview

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

Citations102
Published2022
Admission routes1
Has abstractyes

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