Why adverse outcome pathways need to be FAIR
Main Article Content
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.
Plain language summary
New approach methodologies (NAMs) can detect biological phenomena that occur before they add up to serious problems like cancer, infertility, death, and others. NAMs detect key events (KE) along well-proven and agreed adverse outcome pathways (AOP). If a substance tests positive in a NAM for an upstream KE, this signals an early warning that actual adversity might follow. However, what if the knowledge about these AOPs is a well-kept secret? And what if decision-makers find AOPs too exotic to apply in risk assessment? This is where FAIR comes in! FAIR stands for making information findable, accessible, interoperable and re-useable. It aims to increase availability, usefulness, and trustworthiness of data. Here, we show that by interpreting the FAIR principles beyond a purely technical level, AOPs can ring in a new era of 3Rs applicability ‒ by increasing their visibility and making their creation process more transparent and reproducible.
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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. Environ Toxicol Chem 29, 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. Sci Total Environ 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. J Pharmacol Exp Ther 356, 170-181. doi:10.1124/jpet.115.228239
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. Part Fibre Toxicol 17, 16. doi:10.1186/s12989-020-00344-4
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, 2007628. doi:10.1002/smll.202007628
Ives, C., Campia, I., Wang, R.-L. et al. (2017). Creating a structured adverse outcome pathway knowledgebase via ontology-based annotations. Appl In Vitro Toxicol 3, 298-311. doi:10.1089/aivt.2017.0017
Knapen, D. (2021). Adverse outcome pathways and the paradox of complex simplicity. Environ Toxicol Chem 40, 2950-2952. doi:10.1002/etc.5205
Kumar, A. (2019). The newly available FAERS public dashboard: Implications for health care professionals. Hosp Pharm 54, 75-77. doi:10.1177/0018578718795271
Lindquist, M. (2008). VigiBase, the WHO global ICSR database system: Basic facts. Ther Innov Regul Sci 42, 409-419. doi:10.1177/009286150804200501
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. Front Genet 9, 661. doi:10.3389/fgene.2018.00661
Martens, M., Ammar, A., Riutta, A. et al. (2021). WikiPathways: Connecting communities. Nucleic Acids Res 49, 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. Appl In Vitro Toxicol 8, 2-13. doi:10.1089/aivt.2021.0010
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., Senn, J., Levey, T. et al. (2021). The 2021 update of the EPA’s adverse outcome pathway database. Sci Data 8, 169. doi:10.1038/s41597-021-00962-3
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. Front Toxicol 4, 803983. doi:10.3389/ftox.2022.803983
Nymark, P., Rieswijk, L., Ehrhart, F. et al. (2018). A data fusion pipeline for generating and enriching adverse outcome pathway descriptions. Toxicol Sci 162, 264-275. doi:10.1093/toxsci/kfx252
Nymark, P., Karlsson, H. L., Halappanavar, S. et al. (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. et al. (2018). AOP-DB: A database resource for the exploration of adverse outcome pathways through integrated association networks. Toxicol Appl Pharmacol 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. Toxicol Sci 168, 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, 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 Trans Vis Comp Graph 28, 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 and S. Ram (eds), Advances in Conceptual Modeling (138-147). Vol. 12584. 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, 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. Environ Health Perspect 128, 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. Front Toxicol 5, 1183824. doi:10.3389/ftox.2023.1183824
Wilkinson, M. D., Dumontier, M., Aalbersberg, I. J. et al. (2016). The FAIR guiding principles for scientific data management and stewardship. Sci Data 3, 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. Toxicol Sci 155, 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