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Record W2953289747 · doi:10.12688/f1000research.8705.1

Assessment of pharmacogenomic agreement

2016· preprint· en· W2953289747 on OpenAlexafffund
Zhaleh Safikhani, Nehmé El-Hachem, Rene Quevedo, Petr Smirnov, Anna Goldenberg, Nicolai J. Birkbak, Christopher E. Mason, Christos Hatzis, Leming Shi, Hugo J.W.L. Aerts, John Quackenbush, Benjamin Haibe‐Kains

Bibliographic record

VenueF1000Research · 2016
Typepreprint
Languageen
FieldComputer Science
TopicComputational Drug Discovery Methods
Canadian institutionsMontreal Clinical Research InstituteHospital for Sick ChildrenPrincess Margaret Cancer CentreUniversity of TorontoUniversity Health Network
FundersNational Institute of Biomedical Imaging and BioengineeringNational Institute of Neurological Disorders and StrokeCanadian Cancer Society Research InstituteNational Institutes of HealthNational Cancer InstituteNational Institute on Alcohol Abuse and AlcoholismHigher Education Discipline Innovation ProjectGovernment of OntarioNational Natural Science Foundation of ChinaPershing Square Sohn Cancer Research AllianceNational Supercomputer Centre in GuangzhouCancer Research SocietyNational Heart, Lung, and Blood InstituteWorldQuant FoundationVallee FoundationOntario Institute for Cancer ResearchYale UniversityNational Aeronautics and Space Administration
KeywordsPharmacogenomicsDrug responseDrugMedicineGenomicsComputational biologyPharmacologyBiologyGeneticsGeneGenome

Abstract

fetched live from OpenAlex

In 2013 we published an analysis demonstrating that drug response data and gene-drug associations reported in two independent large-scale pharmacogenomic screens, Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Cell Line Encyclopedia (CCLE), were inconsistent. The GDSC and CCLE investigators recently reported that their respective studies exhibit reasonable agreement and yield similar molecular predictors of drug response, seemingly contradicting our previous findings. Reanalyzing the authors' published methods and results, we found that their analysis failed to account for variability in the genomic data and more importantly compared different drug sensitivity measures from each study, which substantially deviate from our more stringent consistency assessment. Our comparison of the most updated genomic and pharmacological data from the GDSC and CCLE confirms our published findings that the measures of drug response reported by these two groups are not consistent. We believe that a principled approach to assess the reproducibility of drug sensitivity predictors is necessary before envisioning their translation into clinical settings.

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)0.097
metaresearch head score (Gemma)0.289
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: Empirical · Consensus signal: Empirical
Teacher disagreement score0.097
Threshold uncertainty score0.512

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0970.289
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0020.004
Bibliometrics0.0100.009
Science and technology studies0.0010.004
Scholarly communication0.0050.003
Open science0.0020.006
Research integrity0.0020.003
Insufficient payload (model declined to judge)0.0050.001

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 head0.098
GPT teacher head0.474
Teacher spread0.376 · 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
GenreEmpirical

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

Citations35
Published2016
Admission routes2
Has abstractyes

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