A multi-dimensional computational framework of drug-induced hepatotoxicity: integrating molecular structure features with disease pathogenesis.

ABSTRACT: Drug-induced hepatotoxicity (DIH), characterized by diverse phenotypes and complex mechanisms, remains a critical challenge in drug discovery. To systematically decode this diversity and complexity, we propose a multi-dimensional computational framework integrating molecular structure analysis with disease pathogenesis exploration, focusing on drug-induced intrahepatic cholestasis (DIIC) as a representative DIH subtype. First, a graph-based modularity maximization algorithm identified DIIC risk genes, forming a DIIC module and eight disease pathogenesis clusters. Network proximity values between drug targets and DIIC clusters were calculated to define drug-disease relationships. Subsequently, a random forest model combining Mordred molecular descriptors, structural alerts (SAs), and networ

SUBMITTER: Zhong H 

PROVIDER: S-EPMC12415848 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature