sAOP: linking chemical stressors to adverse outcomes pathway networks

Abstract

MOTIVATION\nAdverse outcome pathway (AOP) is a toxicological concept proposed to provide a mechanistic representation of biological perturbation over different layers of biological organization. Although AOPs are by definition chemical-agnostic, many chemical stressors can putatively interfere with one or several AOPs and such information would be relevant for regulatory decision-making.\n\n\nRESULTS\nWith the recent development of AOPs networks aiming to facilitate the identification of interactions among AOPs, we developed a stressor-AOP network (sAOP). Using the cytotoxitiy burst (CTB) approach, we mapped bioactive compounds from the ToxCast data to a list of AOPs reported in AOP-Wiki database. With this analysis, a variety of relevant connections between chemicals and AOP components can be identified suggesting multiple effects not observed in the simplified one-biological perturbation to one-adverse outcome model. The results may assist in the prioritization of chemicals to assess risk-based evaluations in the context of human health.\n\n\nAVAILABILITY\nsAOP is available at http://saop.cpr.ku.dk.\n\n\nSUPPLEMENTARY INFORMATION\nSupplementary data are available at Bioinformatics online.