Why adverse outcome pathways need to be FAIR
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Abstract
Adverse outcome pathways (AOPs) provide evidence for demonstrating and assessing causality between measurable toxicological mechanisms and human or environmental adverse effects. AOPs have gained increasing attention over the past decade and are believed to provide the necessary steppingstone for more effective risk assessment of chemicals and materials and moving beyond the need for animal testing. However, as with all types of data and knowledge today, AOPs need to be reusable by machines, i.e., machine-actionable, in order to reach their full impact potential. Machine-actionability is supported by the FAIR principles, which guide findability, accessibility, interoperability, and reusability of data and knowledge. Here, we describe why AOPs need to be FAIR and touch on aspects such as the improved visibility and the increased trust that FAIRification of AOPs provides.
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Ankley, G. T., Bennett, R. S., Erickson, R. J. et al (2010). Adverse outcome pathways: A conceptual framework to support ecotoxicology research and risk assessment. Environmental Toxicology and Chemistry, 29(3), 730–741. doi:10.1002/etc.34
Carusi, A., Davies, M. R., De Grandis, G. et al. (2018). Harvesting the promise of AOPs: An assessment and recommendations. Science of The Total Environment, 628–629, 1542–1556. doi:10.1016/j.scitotenv.2018.02.015
Carusi, A., Wittwehr, C. and Whelan, M. (2022). Addressing evidence needs in chemicals policy and regulation. Publications Office of the European Union. https://data.europa.eu/doi/10.2760/9130
Edwards, S. W., Tan, Y.-M., Villeneuve, D. L. et al. (2015). Adverse Outcome Pathways—Organizing Toxicological Information to Improve Decision Making. Journal of Pharmacology and Experimental Therapeutics, 356(1), 170–181. doi:10.1124/jpet.115.228239
Halappanavar, S., Nymark, P., Krug, H. F. et al. (2021). Non-Animal Strategies for Toxicity Assessment of Nanoscale Materials: Role of Adverse Outcome Pathways in the Selection of Endpoints. Small, 17(15), 2007628. doi:10.1002/smll.202007628
Halappanavar, S., van den Brule, S., Nymark, P. et al. (2020). Adverse outcome pathways as a tool for the design of testing strategies to support the safety assessment of emerging advanced materials at the nanoscale. Particle and Fibre Toxicology, 17(1), 16. doi:10.1186/s12989-020-00344-4
Ives, C., Campia, I., Wang, R.-L. et al. (2017). Creating a Structured Adverse Outcome Pathway Knowledgebase via Ontology-Based Annotations. Applied In Vitro Toxicology, 3(4), 298–311. doi:10.1089/aivt.2017.0017
Knapen, D. (2021). Adverse Outcome Pathways and the Paradox of Complex Simplicity. Environmental Toxicology and Chemistry, 40(11), 2950–2952. doi:10.1002/etc.5205
Kumar, A. (2019). The Newly Available FAERS Public Dashboard: Implications for Health Care Professionals. Hospital Pharmacy, 54(2), 75–77. doi:10.1177/0018578718795271
Lindquist, M. (2008). VigiBase, the WHO Global ICSR Database System: Basic Facts. Drug Information Journal : DIJ / Drug Information Association, 42(5), 409–419. doi:10.1177/009286150804200501
Martens, M., Ammar, A., Riutta, A. et al. (2021). WikiPathways: Connecting communities. Nucleic Acids Research, 49(D1), D613–D621. doi:10.1093/nar/gkaa1024
Martens, M., Evelo, C. T. and Willighagen, E. L. (2022). Providing Adverse Outcome Pathways from the AOP-Wiki in a Semantic Web Format to Increase Usability and Accessibility of the Content. Applied In Vitro Toxicology, 8(1), 2–13. doi:10.1089/aivt.2021.0010
Martens, M., Verbruggen, T., Nymark, P. et al. (2018). Introducing WikiPathways as a Data-Source to Support Adverse Outcome Pathways for Regulatory Risk Assessment of Chemicals and Nanomaterials. Frontiers in Genetics, 9, 661. doi:10.3389/fgene.2018.00661
Marx-Stoelting, P., Rivière, G., Luijten, M. et al. (2023). A walk in the PARC: developing and implementing 21st century chemical risk assessment in Europe. Arch Toxicol. 97, 893-908. doi:10.1007/s00204-022-03435-7
Mortensen, H. M., Martens, M., Senn, J. et al. (2022). The AOP-DB RDF: Applying FAIR Principles to the Semantic Integration of AOP Data Using the Research Description Framework. Frontiers in Toxicology, 4, 803983. doi:10.3389/ftox.2022.803983
Mortensen, H. M., Senn, J., Levey, T. et al. (2021). The 2021 update of the EPA’s adverse outcome pathway database. Scientific Data, 8(1), 169. doi:10.1038/s41597-021-00962-3
Nymark, P., Rieswijk, L., Ehrhart, F. et al. (2018). A Data Fusion Pipeline for Generating and Enriching Adverse Outcome Pathway Descriptions. Toxicological Sciences, 162(1), 264–275. doi:10.1093/toxsci/kfx252
Nymark, P., Karlsson, H. L., Halappanavar, S. and Vogel, U. (2021). Adverse Outcome Pathway Development for Assessment of Lung Carcinogenicity by Nanoparticles. Front Toxicol 3, 653386. doi:10.3389/ftox.2021.653386
OECD (2018). Users’ Handbook supplement to the Guidance Document for developing and assessing Adverse Outcome Pathways. OECD Series on Adverse Outcome Pathways, No. 1, OECD Publishing, Paris, doi:10.1787/5jlv1m9d1g32-en
OECD (2021). Draft Guidance Document for the scientific review of Adverse Outcome Pathways. Joint Meeting Of The Chemicals Committee And The Working Party On Chemicals, Pesticides And Biotechnology, OECD Publishing, https://www.oecd.org/env/ehs/testing/draft-guidance-document-scientific-review-adverse-outcome-pathways.pdf
Pittman, M. E., Edwards, S. W., Ives, C. and Mortensen, H. M. (2018). AOP-DB: A database resource for the exploration of Adverse Outcome Pathways through integrated association networks. Toxicology and Applied Pharmacology, 343, 71–83. doi:10.1016/j.taap.2018.02.006
Pollesch, N. L., Villeneuve, D. L. and O’Brien, J. M. (2019). Extracting and Benchmarking Emerging Adverse Outcome Pathway Knowledge. Toxicological Sciences, 168(2), 349–364. doi:10.1093/toxsci/kfz006
Postigo, R., Brosch, S., Slattery, J. et al. (2018). EudraVigilance Medicines Safety Database: Publicly Accessible Data for Research and Public Health Protection. Drug Safety, 41(7), 665–675. doi:10.1007/s40264-018-0647-1
Rittenbruch, M., Vella, K., Brereton, M. et al. (2022). Collaborative Sense-Making in Genomic Research: The Role of Visualisation. IEEE Transactions on Visualization and Computer Graphics, 28(12), 4477–4489. doi:10.1109/TVCG.2021.3090746
Schultes, E., Magagna, B., Hettne, K. M. et al. (2020). Reusable FAIR Implementation Profiles as Accelerators of FAIR Convergence. In G. Grossmann & S. Ram (Eds.), Advances in Conceptual Modeling (Vol. 12584, pp. 138–147). Springer International Publishing. doi:10.1007/978-3-030-65847-2_13
Schultes, E. and Magagna, B. (2022). FIP Wizard 3.0 User Guide: Making your FIP. Open Science Framework. https://osf.io/5ygzx
Schultes, E. (2023). The FAIR hourglass: A framework for FAIR implementation. FAIR Connect, 1(1), 13–17. doi:10.3233/FC-221514
U.S. EPA (2022). ORD Staff Handbook for Developing IRIS Assessments. U.S. EPA Office of Research and Development, Washington, DC, EPA/600/R-22/268, 2022. https://cfpub.epa.gov/ncea/iris_drafts/recordisplay.cfm?deid=356370
Whaley, P., Edwards, S. W., Kraft, A. et al. (2020). Knowledge Organization Systems for Systematic Chemical Assessments. Environmental Health Perspectives, 128(12), 125001. doi:10.1289/EHP6994
Wiklund, L., Caccia, S., Pípal, M. et al. (2023). Development of a data-driven approach to Adverse Outcome Pathway network generation: A case study on the EATS-modalities. Frontiers in Toxicology, 5, 1183824. doi:10.3389/ftox.2023.1183824
Wilkinson, M. D., Dumontier, M., Aalbersberg, Ij. J. et al. (2016). The FAIR Guiding Principles for scientific data management and stewardship. Scientific Data, 3(1), 160018. doi:10.1038/sdata.2016.18
Wittwehr, C., Aladjov, H., Ankley, G. et al. (2017). How Adverse Outcome Pathways Can Aid the Development and Use of Computational Prediction Models for Regulatory Toxicology. Toxicological Sciences, 155(2), 326–336. doi:10.1093/toxsci/kfw207
Wittwehr, C., Chang, X., Bisson, W. et al. (2023). Methods2AOP: An International Collaboration to Integrate Assay Annotations into the AOP Key Event Descriptions. Society of Toxicology 62nd Annual Meeting and ToxExpo 2023, Nashville, TN, March 19 - 23, 2023. doi:10.23645/epacomptox.23564160