biostudies-literatureUnknown6(1)Hellgren J<h4>Background</h4>Early detection of drug-induced liver injury (DILI) during drug development is crucial for reducing drug attrition and ensuring the safety of patients. A versatile, biologically interpretable, and dose-dependent screening approach is therefore needed to inform early stop/go decisions and therapeutic margins.<h4>Methods</h4>We have developed AEGIS (Apoptotic Effector Genes In Safety), a preclinical DILI risk screening and prioritization tool that quantifies dose dependent perturbation of apoptosis-regulating transcription factors from transcriptomics data. We profiled transcriptomic responses after short exposures across primary human hepatocytes (PHH), HepG2/C3A cells, RAW 264.7 cells, and an acute Balb/c mouse study. From these profiles, AEGIS provides quantitative riskCommunications medicine48https://www.ebi.ac.uk/biostudies/studies/S-EPMC12827481biostudies-literatureApoptotic signatures allow early and rapid screening of drug-induced liver injury to accelerate drug discovery.PMC12827481Bonetti AKalm MToki NGallon JWilliams DPChaudhari AChouhan BUatay AKarlsson FAndersson PTan JYPryde KElgendy RLindgren JHellgren JSagemark JJohn BfalseApoptotic signatures allow early and rapid screening of drug-induced liver injury to accelerate drug discovery.<h4>Background</h4>Early detection of drug-induced liver injury (DILI) during drug development is crucial for reducing drug attrition and ensuring the safety of patients. A versatile, biologically interpretable, and dose-dependent screening approach is therefore needed to inform early stop/go decisions and therapeutic margins.<h4>Methods</h4>We have developed AEGIS (Apoptotic Effector Genes In Safety), a preclinical DILI risk screening and prioritization tool that quantifies dose dependent perturbation of apoptosis-regulating transcription factors from transcriptomics data. We profiled transcriptomic responses after short exposures across primary human hepatocytes (PHH), HepG2/C3A cells, RAW 264.7 cells, and an acute Balb/c mouse study. From these profiles, AEGIS provides quantitative risk2025-01-01T00:00:00Z2025 Dec2026-06-06T21:38:31.464Z2026-06-05T03:11:35.293ZS-EPMC128274814144445910.1038/s43856-025-01306-7