Expanding biological space coverage enhances the prediction of drug adverse effects in human using in vitro activity profiles

Scientific Reports
Ruili HuangAnton Simeonov

Abstract

In vitro assay data have recently emerged as a potential alternative to traditional animal toxicity studies to aid in the prediction of adverse effects of chemicals on humans. Here we evaluate the data generated from a battery of quantitative high-throughput screening (qHTS) assays applied to a large and diverse collection of chemicals, including approved drugs, for their capacity in predicting human toxicity. Models were built with animal in vivo toxicity data, in vitro human cell-based assay data, as well as in combination with chemical structure and/or drug-target information to predict adverse effects observed for drugs in humans. Interestingly, we found that the models built with the human cell-based assay data performed close to those of the models based on animal in vivo toxicity data. Furthermore, expanding the biological space coverage of assays by including additional drug-target annotations was shown to significantly improve model performance. We identified a small set of targets, which, when added to the current suite of in vitro human cell-based assay data, result in models that greatly outperform those built with the existing animal toxicity data. Assays can be developed for this set of targets to screen compounds...Continue Reading

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Citations

Nov 16, 2018·Journal of the Royal Society of Medicine·Kathy ArchibaldPandora Pound
Jun 19, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yasunari Matsuzaka, Yoshihiro Uesawa
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Jun 10, 2021·Journal of Toxicology and Environmental Health. Part a·Adrienne PhiferMatias S Attene-Ramos
Nov 12, 2018·ACS Biomaterials Science & Engineering·Carley OrtKibret Mequanint

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Methods Mentioned

BETA
structure-based prediction
ELISA

Software Mentioned

RTECS

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