You are here:
AOP-DB: A Database Resource for the Exploration of Adverse Outcome Pathways Through Integrated Association Networks
Citation:
Pittman, M., S. Edwards, C. Ives, AND H. Mortensen. AOP-DB: A Database Resource for the Exploration of Adverse Outcome Pathways Through Integrated Association Networks. TOXICOLOGY AND APPLIED PHARMACOLOGY. Academic Press Incorporated, Orlando, FL, 343:71-83, (2018).
Impact/Purpose:
To address the need for an automated system to relate putative and potential AOPs to useful publically available information, we introduce the AOP-DB, a database resource that stores AOP-associated gene targets and relevant chemicals, diseases, biological pathways, taxonomy, and ontologies. The AOP-DB integrates multiple heterogeneous data sources and types in a single centralized location, and is the first effort of its kind to automatically relate AOP mechanistic information to functional biological entities. The AOP-DB facilitates exploration across multiple levels of biological organization, as well as species-level variation. To enable the exchange of information among regulatory research efforts, the AOP-DB also interfaces between OECD AOP Discovery and Development tools and other EPA toxicology resources, including ToxCast data (Dix et al., 2007) and the EPA Chemistry Dashboards (Richard & Williams, 2002). The AOP-DB seeks to capture the relationships between these diverse data types in order to profile AOPs in a systems biology context, act as a hypothesis-generation tool for assay development, and aid in the discovery of unidentified AOPs. This paper briefly outlines the design and data sources of the AOP-DB, and illustrates the utility of the tool through three use cases: 1) characterizing the biological space of a putative AOP; 2) exploring the biological overlap between a collection of interconnected AOPs; and 3) hypothesis generation for the development of a potential AOP (e.g. an AOP not yet described). Here we illustrate the AOP-DB to be an effective data integration tool for the characterization of known and potential AOPs, as well as a useful interface between OECD and EPA toxicology efforts and the wider landscape of publically available annotation.
Description:
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.
