Why adverse outcome pathways need to be FAIR

Main Article Content

Clemens Wittwehr
Laure-Alix Clerbaux
Stephen Edwards
Michelle Angrish
Holly Mortensen
Annamaria Carusi
Maciej Gromelski
Eftychia Lekka
Vassilis Virvilis
Marvin Martens
Luiz Olavo Bonino da Silva Santos
Penny Nymark

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.

Article Details

How to Cite
Wittwehr, C., Clerbaux, L.-A., Edwards, S., Angrish, M., Mortensen, H., Carusi, A., Gromelski, M., Lekka, E., Virvilis, V., Martens, M., Bonino da Silva Santos, L. O. and Nymark, P. (2023) “Why adverse outcome pathways need to be FAIR”, ALTEX - Alternatives to animal experimentation. doi: 10.14573/altex.2307131.
Section
Articles
References

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

Most read articles by the same author(s)