AOP-DB: A database resource for the exploration of Adverse Outcome Pathways through integrated association networks
Open accessAbstract
The Adverse Outcome Pathway (AOP) framework describes the progression of a toxicity pathway from molecular perturbation to population-level outcome in a series of measurable, mechanistic responses. The controlled, computer-readable vocabulary that defines an AOP has the ability to, automatically and on a large scale, integrate AOP knowledge with publically available sources of biological high-throughput data and its derived associations. To support the discovery and development of putative (existing) and potential AOPs, we introduce the AOP-DB, an exploratory database resource that aggregates association relationships between genes and their related chemicals, diseases, pathways, species orthology information, ontologies, and gene interactions. These associations are mined from publically available annotation databases and are integrated with the AOP information centralized in the AOP-Wiki, allowing for the automatic characterization of both putative and potential AOPs in the context of multiple areas of biological information, referred to here as "biological entities". The AOP-DB acts as a hypothesis-generation tool for the expansion of putative AOPs, as well as the characterization of potential AOPs, through the creation of association networks across these biological entities. Finally, the AOP-DB provides a useful interface between the AOP framework and existing chemical screening and prioritization efforts by the US Environmental Protection Agency.
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Muratov, E. N., Bajorath, J., Sheridan, R. P., Tetko, I. V., Filimonov, D., Poroikov, V., Oprea, T. I., Baskin, I. I., Varnek, A., Roitberg, A., et al. (2020) · Chemical Society Reviews · doi:10.1039/d0cs00098a · Cited by 913 · see citing works
- Authors
- Pittman, M. E., Edwards, S. W., Ives, C., & Mortensen, H. M.
- Affiliations
- Oak Ridge Associated Universities (US)
- Environmental Protection Agency (US)
- Corresponding author
- Mortensen, Holly M.
- Venue
- Toxicology and Applied Pharmacology
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 343
- Pages
- 71-83
- ISSN
- 0041-008X (ISSN-L)
- PMC
- PMC6104822
- OpenAlex
- W2789275540
- Cited by
- 78
- References
- 52
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 8 · 2023: 9 · 2022: 9 · 2021: 13 · 2020: 10 · 2019: 13 · 2018: 3 · 2017: 1
- FWCI
- 3.47
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Toxicology and Applied Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Environmental Protection Agency
- Office of Research and Development
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biomedical Text Mining and Ontologies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Keywords
- adverse outcome pathways, AOP-Wiki, association networks, toxicity pathways, genetic interactions, hypothesis generation, chemical prioritization, compound screening, environmental chemicals, biological ontologies
- MeSH terms
- Adverse Outcome Pathways, Animals, Humans, Databases, Factual, Risk Assessment, Gene Regulatory Networks, Data Mining, Drug-Related Side Effects and Adverse Reactions
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