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Emergent Adverse Outcome Pathways and Their Potential to Contribute Novel Toxicological Knowledge
Citation:
Pollesch, N., J. Olker, AND R. Wang. Emergent Adverse Outcome Pathways and Their Potential to Contribute Novel Toxicological Knowledge. Society of Environmental Toxicology and Chemistry (SETAC) North America 42nd Annual Meeting, Portland, OR, November 14 - 18, 2021. https://doi.org/10.23645/epacomptox.17113727
Impact/Purpose:
Presentation to the Society of Environmental Toxicology and Chemistry (SETAC) North America 42nd Annual Meeting November 2021. The concept of adverse outcome pathways is increasingly adopted as a framework to aid the toxicology paradigm shift from traditional animal testing to in vitro, in silico, and short-term in vivo methods. There have been many AOPs developed by domain subject experts. This study demonstrates the usefulness of semantic network analysis of the user-defined and emergent AOPs to assess biological plausibility and prioritize AOPs for further expert review. This approach highlights the large amount of valuable untapped AOP knowledge and provides a systematic method for evaluating and prioritizing emergent AOPs.
Description:
Adverse outcome pathways (AOPs) are used to encode structured toxicological knowledge. User-contributed online knowledgebases, such as the AOPWiki, contain AOPs that span diverse biological and toxicological domains. When AOPs are shared publicly, contributors are doing more than just disseminating knowledge of their specialties, they are also creating the potential for new knowledge through emergent AOPs across domains. Emergent AOPs result when key events are shared across user-defined AOPs. Recent research shows that emergent AOPs far outnumber user-defined AOPs in the AOPWiki. However, given the diversity of AOPs, emergent AOPs may provide novel toxicological insight, or they may be computational artifacts. Therefore, methods must be developed to assess their biological plausibility and prioritize them for further expert review. This paper demonstrates the usefulness of semantic network analysis of the user-defined and emergent AOPs for this purpose. Results show that unspecified emergent AOPs have, on average, comparable if not higher levels of semantic coherence as user-defined AOPs. These results indicate that emergent AOPs represent a large amount of valuable untapped AOP knowledge and reiterate the value of further enhancing user-contributed public knowledgebases, such as the AOPWiki and broader AOP knowledgebase. The contents of this abstract neither constitute nor necessarily reflect US EPA policy.
URLs/Downloads:
DOI: Emergent Adverse Outcome Pathways and Their Potential to Contribute Novel Toxicological Knowledge
EMERGENT AOPS AND THEIR POTENTIAL - POLLESCH ET AL.PDF (PDF, NA pp, 1602.867 KB, about PDF)