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Record W3027142126 · doi:10.1093/nar/gkaa421

SYNERGxDB: an integrative pharmacogenomic portal to identify synergistic drug combinations for precision oncology

2020· article· en· W3027142126 on OpenAlexafffund
Heewon Seo, Denis Tkachuk, Chantal Ho, Anthony Mammoliti, Aria Rezaie, Benjamin Haibe‐Kains

Bibliographic record

VenueNucleic Acids Research · 2020
Typearticle
Languageen
FieldComputer Science
TopicComputational Drug Discovery Methods
Canadian institutionsVector InstitutePrincess Margaret Cancer CentreOntario Institute for Cancer ResearchUniversity of TorontoUniversity Health Network
FundersCanadian Institutes of Health ResearchOntario Institute for Cancer ResearchGenome Canada
KeywordsPharmacogenomicsDrugBiologyComputational biologyCompendiumCancerCancer cell linesSystems pharmacologyPrecision medicineBioinformaticsPharmacologyCancer cellGenetics

Abstract

fetched live from OpenAlex

Drug-combination data portals have recently been introduced to mine huge amounts of pharmacological data with the aim of improving current chemotherapy strategies. However, these portals have only been investigated for isolated datasets, and molecular profiles of cancer cell lines are lacking. Here we developed a cloud-based pharmacogenomics portal called SYNERGxDB (http://SYNERGxDB.ca/) that integrates multiple high-throughput drug-combination studies with molecular and pharmacological profiles of a large panel of cancer cell lines. This portal enables the identification of synergistic drug combinations through harmonization and unified computational analysis. We integrated nine of the largest drug combination datasets from both academic groups and pharmaceutical companies, resulting in 22 507 unique drug combinations (1977 unique compounds) screened against 151 cancer cell lines. This data compendium includes metabolomics, gene expression, copy number and mutation profiles of the cancer cell lines. In addition, SYNERGxDB provides analytical tools to discover effective therapeutic combinations and predictive biomarkers across cancer, including specific types. Combining molecular and pharmacological profiles, we systematically explored the large space of univariate predictors of drug synergism. SYNERGxDB constitutes a comprehensive resource that opens new avenues of research for exploring the mechanism of action for drug synergy with the potential of identifying new treatment strategies for cancer patients.

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)0.003
metaresearch head score (Gemma)0.006
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: none
GenreCandidate signal: Software · Consensus signal: none
Teacher disagreement score0.010
Threshold uncertainty score0.034

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.006
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0010.002
Bibliometrics0.0040.004
Science and technology studies0.0010.000
Scholarly communication0.0020.001
Open science0.0020.003
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0100.002

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 head0.118
GPT teacher head0.486
Teacher spread0.368 · 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
GenreSoftware

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

Citations49
Published2020
Admission routes2
Has abstractyes

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