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Looking at the BiG picture: incorporating bipartite graphs in drug response prediction

2022· article· en· W4281964006 on OpenAlexafffund
David Earl Hostallero, Yihui Li, Amin Emad

Bibliographic record

VenueBioinformatics · 2022
Typearticle
Languageen
FieldComputer Science
TopicComputational Drug Discovery Methods
Canadian institutionsMcGill UniversityMila - Quebec Artificial Intelligence Institute
FundersNatural Sciences and Engineering Research Council of CanadaInstitut de Valorisation des DonnéesMerck Canada
KeywordsBipartite graphDrug responseComputer scienceLeverage (statistics)PharmacogenomicsPython (programming language)DrugGraphBig dataMachine learningArtificial intelligenceComputational biologyTheoretical computer scienceData miningBioinformaticsBiology

Abstract

fetched live from OpenAlex

MOTIVATION: The increasing number of publicly available databases containing drugs' chemical structures, their response in cell lines, and molecular profiles of the cell lines has garnered attention to the problem of drug response prediction. However, many existing methods do not fully leverage the information that is shared among cell lines and drugs with similar structure. As such, drug similarities in terms of cell line responses and chemical structures could prove to be useful in forming drug representations to improve drug response prediction accuracy. RESULTS: We present two deep learning approaches, BiG-DRP and BiG-DRP+, for drug response prediction. Our models take advantage of the drugs' chemical structure and the underlying relationships of drugs and cell lines through a bipartite graph and a heterogeneous graph convolutional network that incorporate sensitive and resistant cell line information in forming drug representations. Evaluation of our methods and other state-of-the-art models in different scenarios shows that incorporating this bipartite graph significantly improves the prediction performance. In addition, genes that contribute significantly to the performance of our models also point to important biological processes and signaling pathways. Analysis of predicted drug response of patients' tumors using our model revealed important associations between mutations and drug sensitivity, illustrating the utility of our model in pharmacogenomics studies. AVAILABILITY AND IMPLEMENTATION: An implementation of the algorithms in Python is provided in https://github.com/ddhostallero/BiG-DRP. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

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 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)0.003
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: Simulation or modeling
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.192
Threshold uncertainty score0.423

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0030.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0010.000
Scholarly communication0.0000.001
Open science0.0010.001
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 head0.019
GPT teacher head0.256
Teacher spread0.237 · 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 teacher head, 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

Citations30
Published2022
Admission routes2
Has abstractyes

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