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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.
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Submitted on : Monday, April 19, 2021 - 8:57:32 AM
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Alejandro Aguayo-Orozco, Karine Audouze, Troels Siggaard, Robert Barouki, Soren Brunak, et al.. sAOP: linking chemical stressors to adverse outcomes pathway networks. Bioinformatics, Oxford University Press (OUP), 2019, 35 (24), pp.5391-5392. ⟨10.1093/bioinformatics/btz570⟩. ⟨hal-03201557⟩



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