Bayes Optimal Informer Sets for Early-Stage Drug Discovery

DOI10.1111/BIOM.13637zbMATH Open1522.62282OpenAlexW4213204524MaRDI QIDQ6079751FDOQ6079751

Authors Peng Yu, Michael A. Newton 

Publication date 30 October 2023

Published in Biometrics (Search for Journal in Brave)

Full work available at URL https://arxiv.org/abs/2011.06122

zbMATH Keywords

experimental designmatrix completionrankingDirichlet process mixture modelBayes decision rulehigh-throughput screening

Mathematics Subject Classification ID

Applications of statistics to biology and medical sciences; meta analysis (62P10)

Abstract: An important experimental design problem in early-stage drug discovery is how to prioritize available compounds for testing when very little is known about the target protein. Informer based ranking (IBR) methods address the prioritization problem when the compounds have provided bioactivity data on other potentially relevant targets. An IBR method selects an informer set of compounds, and then prioritizes the remaining compounds on the basis of new bioactivity experiments performed with the informer set on the target. We formalize the problem as a two-stage decision problem and introduce the Bayes Optimal Informer SEt (BOISE) method for its solution. BOISE leverages a flexible model of the initial bioactivity data, a relevant loss function, and effective computational schemes to resolve the two-step design problem. We evaluate BOISE and compare it to other IBR strategies in two retrospective studies, one on protein-kinase inhibition and the other on anti-cancer drug sensitivity. In both empirical settings BOISE exhibits better predictive performance than available methods. It also behaves well with missing data, where methods that use matrix completion show worse predictive performance. We provide an R implementation of BOISE at https://github.com/wiscstatman/esdd/BOISE

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