NUTRIM School of Nutrition and Translational Research in Metabolism Introducing WikiPathways to link molecular pathways to Adverse Outcome Pathways Marvin Martens1, Egon Willighagen1 and Chris T Evelo1,2 1 Dept. of Bioinformatics, BiGCaT, Maastricht University, Maastricht, The Netherlands 2 Maastricht Centre for Systems Biology (MaCSBio), Maastricht University, Maastricht, The Netherlands Results Conclusion Most of the molecular and cellular Key Events, and the Key Event Relationships that connect these, on AOP Wiki describe molecular pathways by free-text that are already present on WikiPathways.org or as part of it. Clear descriptions of the Key Events with correct use of ontologies are required to allow linking the Key Events and Key Event Relationships to the molecular pathways and for WikiPathways to become a supportive database for AOPs and assisting in the implementation of omics approaches in regulatory risk assessment. Future work will need to focus on linking AOP Wiki Key Events with their corresponding molecular pathways and entities by improving the ontology annotations, linking these to the Pathway Ontology used in WikiPathways and introducing link-outs on the AOP Wiki. References [1] Ankley GT, Bennett RS, Erickson RJ, Hoff DJ, Hornung MW, Johnson RD, et al. Adverse outcome pathways: A conceptual framework to support ecotoxicology research and risk assessment. Environ Toxicol Chem. 2010 Mar 1;29(3):730–41. [2] Leist M, Ghallab A, Graepel R, Marchan R, Hassan R, Bennekou SH, et al. Adverse outcome pathways: opportunities, limitations and open questions. Arch Toxicol. 2017;91(11):3477–505. [3] Vinken M, Knapen D, Vergauwen L, Hengstler JG, Angrish M, Whelan M. Adverse outcome pathways: a concise introduction for toxicologists. Arch Toxicol [Internet]. 2017 Nov 28;91(11):3697–707. [4] Marx-stoelting P, Braeuning · A, Buhrke · T, Lampen · A, Niemann · L, Oelgeschlaeger · M, et al. Application of omics data in regulatory toxicology: report of an international BfR expert workshop. Arch Toxicol [Internet]. 2015;89:2177–84. [5] Tralau T, Oelgeschläger M, Gürtler R, Heinemeyer G, Herzler M, Höfer T, et al. Regulatory toxicology in the twenty-first century: challenges, perspectives and possible solutions. Arch Toxicol [Internet]. 2015 ;89:823–50. [6] Nymark P, Rieswijk L, Ehrhart F, Jeliazkova N, Tsiliki G, Sarimveis H, et al. A Data Fusion Pipeline for Generating and Enriching Adverse Outcome Pathway Descriptions. Toxicol Sci. 2018;162(1):264–75. Correspondence to: Marvin Martens, BiGCaT ORCID: 0000-0003-2230-0840 marvin.martens@maastrichtuniversity.nl @mmarvinm2 Maastricht University Dept of Bioinformatics http://www.bigcat.unimaas.nl T +3143 388 1343 Background Adverse Outcome Pathway concept The Adverse Outcome Pathway (AOP) has become a useful tool to support regulatory decision making for chemical compounds. AOPs provide a mechanistic representation of toxicological effects, from the initial molecular interaction of a chemical towards an adverse outcome on a biological level relevant for risk assessment (Figure 1A). This will lead to more rapid and cost-effective, high-throughput methods to aid regulatory risk assessment and serving as a basis for generating integrated approaches to testing and assessment [1,2]. To guide the increasing development and use of AOPs, the OECD, JRC and US EPA together launched the AOP knowledge base (Figure 1B) [2,3]. Figure 1: Graphical representation of the Adverse Outcome Pathway concept (A) and the modules of the AOP knowledge base (B). A B AOP knowledge base AOP Wiki Effectopedia Intermediate effects DB AOP Xplorer e. AOP.Portal Objective Our research question is: How can Adverse Outcome Pathways be supported by molecular pathway knowledge (to allow the use of omics approaches)? Figure 3: AOP Wiki statistics tree. Pink nodes indicate elements of predefined vocabularies or identifiers. Figure 2: The Adverse Outcome Pathway portal on WikiPathways.org (left). This portal has a growing