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Accelerating Adverse Outcome Pathway Development Using Publicly Available Data Sources

Noffisat O. Oki, Mark D. Nelms, Shannon M. Bell, Holly M. Mortensen, Stephen W. Edwards.
Current Environmental Health Reports. 2016 DOI: http://dx.doi.org/10.1007/s40572-016-0079-y PMID: 26809562



The adverse outcome pathway (AOP) concept links molecular perturbations with organism and population-level outcomes to support high-throughput toxicity (HTT) testing. International efforts are underway to define AOPs and store the information supporting these AOPs in a central knowledge base; however, this process is currently labor-intensive and time-consuming. Publicly available data sources provide a wealth of information that could be used to define computationally predicted AOPs (cpAOPs), which could serve as a basis for creating expert-derived AOPs in a much more efficient way. Computational tools for mining large datasets provide the means for extracting and organizing the information captured in these public data sources. Using cpAOPs as a starting point for expert-derived AOPs should accelerate AOP development. Coupling this with tools to coordinate and facilitate the expert development efforts will increase the number and quality of AOPs produced, which should play a key role in advancing the adoption of HTT testing, thereby reducing the use of animals in toxicity testing and greatly increasing the number of chemicals that can be tested.


Figure 1. Overview of the AOP framework.

All data sources listed here are also referenced in Table 1.
Data resources containing data in the molecular to cellular levels of biological organization.
Data resources containing data in the cellular to tissue levels of biological organization.
Data resources containing data in the tissue to individual levels of biological organization.


Table 1. List of AOP data source, level of biological organization, and data type included.