sAOP: linking chemical stressors to adverse outcomes pathway networks

Abstract

Motivation: Adverse 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.

Results: With 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.

Availability and implementation: sAOP is available at http://saop.cpr.ku.dk.

Supplementary information: Supplementary data are available at Bioinformatics online.

Fig. 1.

Results of the sAOP network for the chemical ‘phenanthrene’. A color scheme is defined for each element of the network. The arrows show the edges directionality