Integration of Adverse Outcome Pathways, Causal Networks and 'Omics to Support Chemical Hazard Assessment.

ABSTRACT: Several approaches have been used in an attempt to simplify and codify the events that lead to adverse effects of chemicals including systems biology, 'omics, in vitro assays and frameworks such as the Adverse Outcome Pathway (AOP). However, these approaches are generally not integrated despite their complementary nature. Here we propose to integrate toxicogenomics data, systems biology information and AOPs using causal biological networks to define Key Events in AOPs. We demonstrate this by developing a causal subnetwork of 28 nodes that represents the Key Event of regenerative proliferation - a critical event in AOPs for liver cancer. We then assessed the effects of three chemicals known to cause liver injury and cell proliferation (carbon tetrachloride, aflatoxin B₁, t

SUBMITTER: Perkins EJ 

PROVIDER: S-EPMC8987526 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature