A large-scale human toxicogenomics resource for drug-induced liver injury prediction.

ABSTRACT: Drug-Induced Liver Injury (DILI) remains one of the most critical challenges in drug development, causing patient safety concerns, clinical trial failures and drug withdrawals. We introduce ToxPredictor, a toxicogenomics framework combining RNA-seq data from primary human hepatocytes with pharmacokinetic data to predict dose-resolved DILI risks and safety margins. At its core is DILImap, an RNA-seq library tailored for DILI research, comprising 300 compounds at multiple concentrations. ToxPredictor achieves 88% sensitivity at 100% specificity in blind validation, outperforming state-of-the-art methods. It flagged recent phase III clinical failures, including Evobrutinib, TAK-875, and BMS-986142, overlooked by animal studies. Beyond prediction, ToxPredictor provides mechanistic insights int

SUBMITTER: Bergen V 

PROVIDER: S-EPMC12615732 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature