A Mechanistic Framework for Integrating Chemical Structure and High-Throughput Screening Results to Improve Toxicity Predictions.

ABSTRACT: Adverse Outcome Pathways (AOPs) establish a connection between a molecular initiating event (MIE) and an adverse outcome. Detailed understanding of the MIE provides the ideal data for determining chemical properties required to elicit the MIE. This study utilized high-throughput screening data from the ToxCast program, coupled with chemical structural information, to generate chemical clusters using three similarity methods pertaining to nine MIEs within an AOP network for hepatic steatosis. Three case studies demonstrate the utility of the mechanistic information held by the MIE for integrating biological and chemical data. Evaluation of the chemical clusters activating the glucocorticoid receptor identified activity differences in chemicals within a cluster. Comparison of the estrogen re

SUBMITTER: Nelms MD 

PROVIDER: S-EPMC9910356 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature