Bayesian joint modeling of chemical structure and dose response curves

DOI10.1214/21-AOAS1461zbMATH Open1478.62337arXiv1912.12228OpenAlexW3172640384MaRDI QIDQ2247494FDOQ2247494

David Dunson, Amy H. Herring, Matthew W. Wheeler, Kelly R. Moran

Publication date: 17 November 2021

Published in: The Annals of Applied Statistics (Search for Journal in Brave)

Abstract: Today there are approximately 85,000 chemicals regulated under the Toxic Substances Control Act, with around 2,000 new chemicals introduced each year. It is impossible to screen all of these chemicals for potential toxic effects either via full organism in vivo studies or in vitro high-throughput screening (HTS) programs. Toxicologists face the challenge of choosing which chemicals to screen, and predicting the toxicity of as-yet-unscreened chemicals. Our goal is to describe how variation in chemical structure relates to variation in toxicological response to enable in silico toxicity characterization designed to meet both of these challenges. With our Bayesian partially Supervised Sparse and Smooth Factor Analysis ($ext{BS}^{3}extFA$) model, we learn a distance between chemicals targeted to toxicity, rather than one based on molecular structure alone. Our model also enables the prediction of chemical dose-response profiles based on chemical structure (that is, without in vivo or in vitro testing) by taking advantage of a large database of chemicals that have already been tested for toxicity in HTS programs. We show superior simulation performance in distance learning and modest to large gains in predictive ability compared to existing methods. Results from the high-throughput screening data application elucidate the relationship between chemical structure and a toxicity-relevant high-throughput assay. An R package for $ext{BS}^{3}extFA$ is available online at https://github.com/kelrenmor/bs3fa.

Full work available at URL: https://arxiv.org/abs/1912.12228

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zbMATH Keywords

dimension reductionfunctional predictionQSARhigh-throughput screeningtoxicitydistance learningToxCast

Mathematics Subject Classification ID

Factor analysis and principal components; correspondence analysis (62H25) Applications of statistics to biology and medical sciences; meta analysis (62P10) Inference from stochastic processes and prediction (62M20) Functional data analysis (62R10)

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Cited In (8)

• Bayesian additive adaptive basis tensor product models for modeling high dimensional surfaces: an application to high‐throughput toxicity testing
• Hierarchical Bayesian Modeling of Pharmacophores in Bioinformatics
• Statistical methods for automated drug susceptibility testing: Bayesian minimum inhibitory concentration prediction from growth curves
• Title not available (Why is that?)
• A Bayesian Approach to Dose-Response Assessment and Synergy and Its Application to In Vitro Dose-Response Studies
• bs3fa
• BMA‐Mod: A Bayesian model averaging strategy for determining dose‐response relationships in the presence of model uncertainty
• A Bayesian model of dose-response for cancer drug studies

Uses Software

• R
• JIVE
• GitHub

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