Identifying multiscale translational safety biomarkers using a network-based systems approach.

ABSTRACT: Animal testing is the current standard for drug and chemicals safety assessment, but hazards translation to human is uncertain. Human in vitro models can address the species translation but might not replicate in vivo complexity. Herein, we propose a network-based method addressing these translational multiscale problems that derives in vivo liver injury biomarkers applicable to in vitro human early safety screening. We applied weighted correlation network analysis (WGCNA) to a large rat liver transcriptomic dataset to obtain co-regulated gene clusters (modules). We identified modules statistically associated with liver pathologies, including a module enriched for ATF4-regulated genes as associated with the occurrence of hepatocellular single-cell necrosis, and

SUBMITTER: Callegaro G 

PROVIDER: S-EPMC9988559 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature