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Comprehensive mapping of the AOP-Wiki database: identifying biological and disease gaps

identifying biological and disease gaps
Authors: Thomas Jaylet; Thibaut Coustillet; Nicola M. Smith; Barbara Viviani; Birgitte Lindeman; Lucia Vergauwen; Oddvar Myhre; +27 Authors

Comprehensive mapping of the AOP-Wiki database: identifying biological and disease gaps

Abstract

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.

Countries
Belgium, France, France, France, Italy, Denmark, Greece
Keywords

570, AOP network; PARC; adverse outcome pathway; diseases; immunotoxicity; neurotoxicity; nongenotoxic carcinogenesis, Bioinformatics, Nongenotoxic carcinogenesis, Τοξικολογία, nongenotoxic carcinogenesis, 610, Diseases, Toxicology, diseases, Adverse outcome pathway, RA1190-1270, neurotoxicity, Neurotoxicity, Immunotoxicity, Επιδημίες. Επιδημιολογία, AOP network, PARC, Molecular Biology, Βιοπληροφορική, immunotoxicity, Pharmacology. Therapy, Μοριακή Βιολογία, Epidemics. Epidemiology, adverse outcome pathway, adverse outcome pathway AOP network immunotoxicity neurotoxicity nongenotoxic carcinogenesis diseases PARC, [SDV.TOX] Life Sciences [q-bio]/Toxicology, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Toxicology. Poisons

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    selected citations
    These citations are derived from selected sources.
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    15
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
15
Top 10%
Average
Top 10%
Green
gold