Alejandro Aguayo-Orozco1, Karine Audouze2, Troels Siggaard1, Robert Barouki2, Søren Brunak1, Olivier Taboureau1,3. 1. Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DK-2200, Denmark. 2. Environmental Toxicity, Therapeutic Targets, Cellular Signaling and Biomarkers (T3S) Unit, Université de Paris, INSERM UMR-S 1124, Paris, France. 3. Université de Paris, INSERM U1133, Computational Modeling of Protein-Ligand Interactions group, CNRS UMR 8251, Unit of Functional and adaptive Biology, Paris, France.
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.
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.
Authors: Karine Audouze; Elias Zgheib; Khaled Abass; Asma H Baig; Isabel Forner-Piquer; Henrik Holbech; Dries Knapen; Pim E G Leonards; Diana I Lupu; Saranya Palaniswamy; Arja Rautio; Maria Sapounidou; Olwenn V Martin Journal: Front Toxicol Date: 2021-12-21