European Partnership for the Assessment of Risks from Chemicals

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Published March 8, 2024 | Version v1
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Comprehensive mapping of the AOP-Wiki database: identifying biological and disease gaps

Authors/Creators

  • 1. ROR icon Université Paris Cité
  • 2. ROR icon Inserm
  • 3. ROR icon Norwegian Institute of Public Health
  • 4. università degli Studi di Milano
  • 5. ROR icon University of Antwerp
  • 6. medical university of Innsbruck
  • 7. ROR icon University of Southern Denmark
  • 8. ROR icon Aristotle University of Thessaloniki
  • 9. ROR icon National Hellenic Research Foundation
  • 10. ROR icon Istituto Universitario di Studi Superiori di Pavia
  • 11. ROR icon University of Cologne
  • 12. ROR icon Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
  • 13. ROR icon European Commission
  • 14. ROR icon Joint Research Centre
  • 15. ROR icon Leibniz Institute of Environmental Medicine
  • 16. ROR icon Heinrich Heine University Düsseldorf
  • 17. Swiss Centre for Applied Human Toxicology
  • 18. DNTOX gmbH
  • 19. ROR icon Université Sorbonne Paris Nord
  • 20. ROR icon Centre National de la Recherche Scientifique

Description

Introduction: The Adverse Outcome Pathway (AOP) concept facilitates rapid hazard assessment for human health risks. AOPs are constantly evolving, their number is growing, and they are referenced in the AOP-Wiki database, which is supported by the OECD. Here, we present a study that aims at identifying well-defined biological areas, as well as gaps within the AOP-Wiki for future research needs. It does not intend to provide a systematic and comprehensive summary of the available literature on AOPs but summarizes and maps biological knowledge and diseases represented by the already developed AOPs (with OECD endorsed status or under validation).

Methods: Knowledge from the AOP-Wiki database were extracted and prepared for analysis using a multi-step procedure. An automatic mapping of the existing information on AOPs (i.e., genes/proteins and diseases) was performed using bioinformatics tools (i.e., overrepresentation analysis using Gene Ontology and DisGeNET), allowing both the classification of AOPs and the development of AOP networks (AOPN).

Results: AOPs related to diseases of the genitourinary system, neoplasms and developmental anomalies are the most frequently investigated on the AOP-Wiki. An evaluation of the three priority cases (i.e., immunotoxicity and non-genotoxic carcinogenesis, endocrine and metabolic disruption, and developmental and adult neurotoxicity) of the EU-funded PARC project (Partnership for the Risk Assessment of Chemicals) are presented. These were used to highlight under- and over-represented adverse outcomes and to identify and prioritize gaps for further research.

Discussion: These results contribute to a more comprehensive understanding of the adverse effects associated with the molecular events in AOPs, and aid in refining risk assessment for stressors and mitigation strategies. Moreover, the FAIRness (i.e., data which meets principles of findability, accessibility, interoperability, and reusability (FAIR)) of the AOPs appears to be an important consideration for further development.

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Additional details

Funding

European Commission
PARC - Partnership for the Assessment of Risks from Chemicals 101057014

Dates

Available
2024-03-08