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Accelerating Adverse Outcome Pathway Development Using Publicly Available Data Sources

  • Mechanisms of Toxicity (CJ Mattingly, Section Editor)
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Abstract

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.

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Acknowledgments

The authors thank all the members of the AOP-KB development team for their helpful discussions and the following for feedback on an early draft of this paper: Kevin Crofton, Lyle Burgoon, Hristo Aladjov, Ed Perkins, Natalia Garcia-Reyero, and Clemens Wittwehr. They also thank Ingrid Druwe and Michelle Angrish for their helpful comments on the manuscript. The information in this document has been funded wholly (or in part) by the US Environmental Protection Agency. It has been subjected to review by the National Health and Environmental Effects Research Laboratory and approved for publication. Approval does not signify that the contents reflect the views of the agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.

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Author notes

  1. Shannon M. Bell

    Present address: ILS/Contractor Supporting the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), Research Triangle Park, NC, USA

Authors and Affiliations

  1. Oak Ridge Institute for Science and Education, Oak Ridge, TN, USA

    Noffisat O. Oki, Mark D. Nelms & Shannon M. Bell

  2. Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, 109 T.W. Alexander Drive, Mail Code: B305-01, Research Triangle Park, NC, 27709, USA

    Noffisat O. Oki, Mark D. Nelms, Shannon M. Bell & Stephen W. Edwards

  3. Genomics Research Core, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA

    Holly M. Mortensen

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Noffisat Oki, Mark Nelms, Shannon Bell, Holly Mortensen, and Stephen Edwards declare that they have no conflict of interest.

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Oki, N.O., Nelms, M.D., Bell, S.M. et al. Accelerating Adverse Outcome Pathway Development Using Publicly Available Data Sources. Curr Envir Health Rpt 3, 53–63 (2016). https://doi.org/10.1007/s40572-016-0079-y

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