The FAIR AOP Roadmap for 2025: Advancing Findability, Accessibility, Interoperability, and Re-Usability of Adverse Outcome Pathways

Adverse Outcome Pathways (AOPs) describe the mechanistic interaction of biological entities that produce an adverse response. How we catalog these interactions and associations contributes to our ability to understand mechanistic effects and apply this knowledge to New Approach Methodologies (NAMs) that have the potential to reduce animal testing in chemical and material safety assessments. Making AOP data and supporting metadata FAIR (findable, accessible, interoperable, and reusable) depends on the coordination of FAIR supporting tools that implement and process AOP data and related metadata, referred to as FAIR Enabling Resources, and the establishment of coordinated and consensus bioinformatic methods. Here we describe current FAIR AOP efforts in addressing the FAIRification of AOP mechanistic data and metadata, as well as the international, collaborative efforts to document, and improve the use and reliability of AOP information. These coordinated efforts will contribute to the standard of AOP mechanistic data and application to 21st Century risk assessment.

Impact/Purpose

Adverse Outcome Pathways (AOPs) describe the mechanistic interaction of biological entities that result in an adverse response. How we catalog these interactions and associations contributes to our ability to understand mechanistic effects and apply this knowledge to New Approach Methodologies (NAMs). Related, our ability to connect AOPs to other types of biological and toxicological data defines their utility, reuse, and interoperability and whether AOP data will have the potential to reduce animal testing in chemical and material safety assessments in the future. Wittwehr,et al. (2024) describe why AOPs need to be FAIR and underline the pragmatic necessity of machine-actionability for AOPs to reach their full-impact. The FAIRAOP Cluster Workgroup is an international group of academic, government and industry partners with a shared interest in the use and reliability of AOP information. With the recent proliferation of methods and tools that aim to map AOP data and metadata to biomedical entities, the FAIR AOP ClusterWorkgroup has formed with the objective to address the coordinated standardization and identification of mechanistic information and data associated withAOPs. The FAIR AOP Cluster Workgroup has reviewed AOP projects and initiatives with related data challenges in an effort to identify synergies and promote coherence. This effort facilitates standardized AOP annotation, and promotes machine actionability and increased trustability of AOP information, whiledirecting community contribution through an open data model.Making AOP data and supporting metadata FAIR (findable, accessible, interoperable, and re-usable) depends on the coordination and active orchestration of FAIR Enabling Resources and the establishment of consensus formats and description of processes. The current FAIR AOP Cluster Workgroup efforts to document existing AOP projects and tools that implement mechanistic data, metadata, and related biomedical information are described.We discuss existing AOP tools and current approaches for mapping mechanistic data types to AOPs. We review the outcomes of international and collaborative AOP coordination efforts (ELIXIR, The Environmental Health Language Collaborative's 2025 AOP Standards Workshop, the AOP FAIRImplementation Profile) and the progress made in development of FAIR AOP standards. We describe the recent FAIR AOP Cluster Workgroup efforts andprogress in defining a FAIR AOP ROADMAP. We also position the FAIR AOP Cluster work among other initiatives, efforts and projects that aim at improvingthe AOP-Wiki and the AOP Framework, and describe how our results and recommendations will impact the planning for AOP-Wiki 3.0.The FAIR AOP Roadmap describes how, through coordinated efforts, AOP mechanistic data and metadata and related biomedical entities canbe incorporated to improve the FAIR standards of the AOP framework. These efforts will affect future iterations of AOP FAIR enabling resources including the AOP-Wiki repository, and the trustability of AOP information for inclusion risk assessment and regulatory efforts.

Citation

Mortensen, H., M. Gromelski, V. Hench, M. Martens, C. Wittwehr, S. Kumar, V. Kumar, K. Audouze, V. Virvilis, P. Nymark, M. Angrish, I. Lynch, S. Edwards, B. Magagna, AND M. Wojewodzic. The FAIR AOP Roadmap for 2025: Advancing Findability, Accessibility, Interoperability, and Re-Usability of Adverse Outcome Pathways. Elsevier B.V., Amsterdam, NETHERLANDS, 35:100368, (2025). [DOI: 10.1016/j.comtox.2025.100368]

DOI: The FAIR AOP Roadmap for 2025: Advancing Findability, Accessibility, Interoperability, and Re-Usability of Adverse Outcome Pathways