Frontiers in Toxicology, Journal Year: 2023, Volume and Issue: 5

Published: Nov. 17, 2023

Introduction: While targeted investigation of key toxicity pathways has been instrumental for biomarker discovery, unbiased and holistic analysis transcriptomic data provides a complementary systems-level perspective. However, in systematic context, this approach yet to receive comprehensive methodical implementation. Methods: Here, we took an integrated bioinformatic by re-analyzing publicly available MCF7 cell TempO-seq 44 ToxCast chemicals using alternative pipeline demonstrate the power approach. The original study focused on analyzing gene signature comparing them vitro biological pathway altering concentrations determined from HTS assays. Our workflow, comparison, involves sequential differential expression, set enrichment, benchmark dose modeling, identification commonly perturbed network visualization. Results: Using approach, identified dose-responsive molecular changes, pathways, points departure untargeted manner. Critically, modeling based recapitulated apical endpoints, while also revealing additional mechanisms missed single endpoint analyses. Discussion: This systems-toxicology multifaceted insights into complex effects chemical exposures. work highlights importance data-driven techniques, alongside methods, comprehensively evaluating initiating events, dose-response relationships, pathways. Overall, integrating omics assays with robust bioinformatics holds promise improving risk assessment advancing new methodologies (NAMs).

Language: Английский