Semantic modelling of Adverse Outcome Pathways and the implementation in reproducible workflows

The purpose of Adverse Outcome Pathways is to organize mechanistic knowledge on toxicological processes upon exposure to a stressor leading to an Adverse Outcome through a series of Key Events (KEs). The implementation of this concept for risk assessments is aimed to facilitate the replacement, reduction, refinement (3Rs) of animal testing. Qualitative descriptions of AOPs are generally stored in the public AOP-Wiki. However, its content remains relatively isolated and is only manually queryable or through downloading the full dataset, limiting the capabilities of this rich resource of toxicological knowledge. We tackled this AOP-Wiki limitation by converting the data into the AOP-Wiki Resource Description Framework (RDF) as triples. We used over twenty ontologies for the semantic annotation of property-object relations, and we introduced over 10,000 database descriptors for chemicals, genes and proteins. The AOP-Wiki RDF has been made available at aopwiki.rdf.bigcat-bioinformatics.org where SPARQL queries can be used to extract information and answer biological and toxicological questions, manually or computationally. As a demonstration of its usability, we developed a Jupyter notebook that adds information to an AOP of interest and looks for supporting experimental data from ToxCast and TG-GATES based on the molecular targets and stressor chemicals. Then, it performs pathway enrichment analysis with the transcriptomics data using molecular pathways from WikiPathways. Overall, the AOP-Wiki RDF improves the accessibility and interoperability of the database, providing additional ways of querying the data and enabling the implementation in automated workflows. By focusing on increasing the machine-readability of AOPs and using consistent vocabularies and ontologies, AOPs become an increasingly useful tool for integrating toxicological knowledge and data, thereby increasing the effectiveness of the concept and addressing the 3Rs in toxicological studies. Poster presented at SWAT4HCLS 2022 (2022).