Deriving time-concordant event cascades from gene expression data: A case study for Drug-Induced Liver Injury (DILI).

ABSTRACT: Adverse event pathogenesis is often a complex process which compromises multiple events ranging from the molecular to the phenotypic level. In toxicology, Adverse Outcome Pathways (AOPs) aim to formalize this as temporal sequences of events, in which event relationships should be supported by causal evidence according to the tailored Bradford-Hill criteria. One of the criteria is whether events are consistently observed in a certain temporal order and, in this work, we study this time concordance using the concept of "first activation" as data-driven means to generate hypotheses on potentially causal mechanisms. As a case study, we analysed liver data from repeat-dose studies in rats from the TG-GATEs database which comprises measurements across eight timepoints, ranging from 3 hours to 4

SUBMITTER: Liu A 

PROVIDER: S-EPMC9292124 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature