AOP-DB: The Adverse Outcome Pathway Database
Monday, 8 April 2019, 16:00 CET
Presenters: Holly Mortensen, Ph.D. (US EPA), Phillip Langley (ORAU-SSC) and Trevor Levey (ORAU-SSC)
The EPA Adverse Outcome Pathway Database (AOP-DB) is currently an internal EPA SQL database that supports discovery and development of putative and potential AOPs. The AOP-DB aggregates relationships between AOP-gene targets, chemical, disease, tissue, pathway, species orthology information, ontologies and gene interactions to characterize the impacts of chemicals to human health and the environment. The AOP-DB serves as a hypothesis generation and decision support tool for case study development. Associations are sourced from public annotation to provide biological context and are integrated with AOP information centralized in the AOP-Wiki. The AOP-DB allows for fast, automatic AOP profiling and exploration that gives a broad, systems-level overview of the biological context of AOPs, thus dramatically expediting predictive toxicology efforts. The long-term significance and impact of the AOP-DB tool is the continued translation of AOP biological context, and the ability to associate these data between and across AOPs, and with assay, chemical, and disease endpoints.
We will present the updated version of the AOP-DB, which includes an increased number of adverse outcomes and corresponding key events derived from direct integration of the AOPWiki XML. We will highlight how the database was originally envisioned, and case study examples of how the database can be used. We will walk through example queries using the development version of the AOP-DB frontend user interface. We will also discuss efforts underway to incorporate AOP-tissue specific network generation, and population-level characterization for AOP multilocus networks.
*This abstract does not reflect EPA Policy
Short Bio - Holly M. Mortensen, Ph.D.
Holly Mortensen received her BS from the University of California, Davis, her M.Sc. from Stanford University, and her Ph.D. in Human Genetics from the University of Maryland, College Park. Dr. Mortensen completed her postdoctoral work at the EPA’s National Center for Computational Toxicology, where her projects included defining toxicity related pathways for annotated human genes, using chemical and disease association and drug target information, data implemented in assay prioritization efforts for the EPA’s ToxCast program. Dr. Mortensen has served as the acting Assistant Laboratory Director and the matrix interface for the Chemical Safety and Sustainability and Human Health Risk Assessment programs for the National Health and Environmental Effects Research Laboratory (NHEERL). Dr. Mortensen’s current research focuses on computational approaches to characterizing human susceptibility in relation to adverse outcome pathways of toxicological interest.