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Record W4399390779 · doi:10.1038/s41597-024-03443-5

The Pan-Canadian Chemical Library: A Mechanism to Open Academic Chemistry to High-Throughput Virtual Screening

2024· article· en· W4399390779 on OpenAlexafffundabout
Corentin Bedart, Grace K. Shimokura, F. G. West, Tabitha E. Wood, Robert A. Batey, John J. Irwin, Matthieu Schapira

Bibliographic record

VenueScientific Data · 2024
Typearticle
Languageen
FieldComputer Science
TopicComputational Drug Discovery Methods
Canadian institutionsUniversity of WinnipegUniversity of AlbertaStructural Genomics ConsortiumUniversity of Toronto
FundersNational Institute of General Medical SciencesGenentechEuropean Federation of Pharmaceutical Industries and AssociationsUniversity of TorontoOntario Genomics InstituteMerck KGaAAlliance de recherche numérique du CanadaNational Institutes of HealthOntario GenomicsGenome CanadaMcGill UniversityBayerPfizerBristol-Myers Squibb
KeywordsChemical spaceDrug discoveryWorkflowVirtual screeningComputer scienceChemical libraryData scienceCheminformaticsChemical databaseProcess (computing)Mechanism (biology)ChemistryChemical biologyResource (disambiguation)NanotechnologySmall moleculeDatabasePhysicsMaterials scienceComputational chemistryOrganic chemistry

Abstract

fetched live from OpenAlex

Computationally screening chemical libraries to discover molecules with desired properties is a common technique used in early-stage drug discovery. Recent progress in the field now enables the efficient exploration of billions of molecules within days or hours, but this exploration remains confined within the boundaries of the accessible chemistry space. While the number of commercially available compounds grows rapidly, it remains a limited subset of all druglike small molecules that could be synthesized. Here, we present a workflow where chemical reactions typically developed in academia and unconventional in drug discovery are exploited to dramatically expand the chemistry space accessible to virtual screening. We use this process to generate a first version of the Pan-Canadian Chemical Library, a collection of nearly 150 billion diverse compounds that does not overlap with other ultra-large libraries such as Enamine REAL or SAVI and could be a resource of choice for protein targets where other libraries have failed to deliver bioactive molecules.

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

Direct model labels (unvalidated)

Per-model category and study-design labels from the labeling rounds. They are machine output, unvalidated, and the disagreement between models ships as data. No study design here is MEDLINE-validated yet.

Model armCategoriesStudy designConfidence
gemmaOpen science
Domain: not available · Genre: Methods
About the Canadian research system: yes · About a Canadian topic: no
Not applicablemedium
gptno category
Domain: not available · Genre: Dataset
About the Canadian research system: yes · About a Canadian topic: yes
Not applicablelow
models splitAgreement compares identical category sets and study designs across arms.

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)0.002
metaresearch head score (Gemma)0.004
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesOpen science
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.997
Threshold uncertainty score0.192

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.004
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0030.005
Science and technology studies0.0020.002
Scholarly communication0.0020.001
Open science0.0030.004
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0110.005

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 head0.069
GPT teacher head0.351
Teacher spread0.282 · 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

Labeled directly by 2 models reading the full record.

Open science

The models disagree on parts of this classification; every voice is preserved in the section at the end of the page.

Study designNot applicable
Domainnot available
GenreMethods · Dataset

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

Citations10
Published2024
Admission routes3
Has abstractyes

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