S15-02 New Approaches to Data and Model Integration of Adverse Outcome Pathway information in the EPA AOP-DB

Abstract

Adverse Outcome Pathways (AOPs) is a conceptual framework that describes the mechanistic progression of key biological events that result in an adverse response. How we catalog these entities and interactions enhances our ability to understand mechanistic effects and subsequently toxicological outcomes relevant to human health. Structured implementation of AOP knowledge contributes to New Approach Methodologies (NAMs) and further development of machine learning and artificial intelligence (AI) utilization for regulatory objectives.

The longevity and success of database/knowledgebase and infrastructure projects have typically been hampered by inconsistent and limited funding. This has clear effects on data sustainability practices, quality of data, and data reuse policies. For AOPs, improving consistent mapping to other types of biological and toxicological data will increase utility, reuse, and interoperability. For example, integrating FAIR (findable, accessible, interoperable, and re-usable) data standards is a good approach, but is reliant on 3^rd party tools. One such tool, the EPA Adverse Outcome Pathway Database (AOP-DB), integrates multiple publicly available resources, extending ontology mapping of AOPs to the mapping of molecular and mechanistic componentsincluding biomedical entities (e.g.,gene, protein, biological pathway, disease, tissue, assay, etc).Since the AOP-DB was created, additional tools have been initiated to improve automatic and systematic parsing, machine-actionability of AOP data to elucidate biological mechanism, and mapping to (meta)data. These tools are necessarybecause the AOP-Wiki, the primary repository of AOP information, does not programmatically map to this type of information. As a result, there is no consistency across AOPs in FAIR reporting standards related to biomedical entity mapping or the human/machine readability within a given AOP. Currently, no 3^rd party mapping of biomedical information pertaining to an AOP feeds into the AOP-Wiki repository. Standardization/harmonization of AOP (meta)data and defining AOP biomedical data lifecycles will facilitate the machine-actionability of AOPs and improve trust, transparency and accessibility.

Four independent, expert workgroups have been formed to address FAIR AOP data standards: the FAIR AOP Cluster Workgroup; the Elixer Toxicology Community; the Environmental Health Language Collaborative AOP Standards Workgroup; and the AOP Ontology Workgroup. These workgroups are currently interacting todevelop a FAIR AOP Roadmap to ensure that AOP data and related biomedical information are easily accessible and interoperable for researchers across different disciplines (e.g., AOP, toxicology, biomedical, regulatory). Here we report on the current direction of the OECD, WPHA, SAAOP, and expert workgroups to improve standards for AOP biomedical entity mapping and coordinate this information. This abstract does not reflect EPA Policy.