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Creating a Structured Adverse Outcome Pathway Knowledgebase via Ontology-Based Annotations
Citation:
Ives, C., I. Campia, R. Wang, C. Wittwehr, AND S. Edwards. Creating a Structured Adverse Outcome Pathway Knowledgebase via Ontology-Based Annotations. Applied In Vitro Toxicology. Mary Ann Liebert, Inc., Larchmont, NY, 3(4):298-311, (2017).
Impact/Purpose:
This work describes efforts to expand the AOP ontology developed as part of the international AOP-KB effort via the incorporation of existing biological ontologies. This work is essential for the long-term sustainability of AOP development and use. First, the expert-derived AOPs housed in the AOP-KB must be identifiable by controlled terminology to promote interoperability among the different modules of the knowledgebase. Second, formal descriptions of the key events will facilitate the emergence of AOP networks, which are essential for capturing the biological complexity that is lost when defining individual AOPs. In addition, having key events tied to biological ontologies is necessary for the incorporation of computationally predicted AOPs derived from data mining of toxicological databases because these AOPs are built using the biological objects as described in the formal ontologies. By using the same terminology for both expert-derived and computationally predicted AOPs, we are able to compare the two via automated methods rather than extensive manual curation. Finally, having the key events within an AOP tied to formal biological ontologies will promote direct use of the AOP information by computational methods and should facilitate the development of computational models describing the AOPs and AOP networks.
Description:
The Adverse Outcome Pathway (AOP) framework is increasingly used to integrate data based on traditional and emerging toxicity testing paradigms. As the number of AOP descriptions has increased, so has the need to define the AOP in computable terms. Herein, we present a comprehensive annotation of 172 AOPs housed in the AOP-Wiki as of December 4, 2016, using terms from existing biological ontologies. AOP Key Events (KEs) were assigned ontology terms using a concept called the Event Component, which consists of a Process, an Object, and an Action term, with each term originating from ontologies and other controlled vocabularies. Annotation of KEs with ontology classes from 14 ontologies and controlled vocabularies resulted in a total of 685 KEs being annotated with a total of 809 Event Components. A set of seven conventions resulted, defining the annotation of KEs via Event Components. This expanded annotation of AOPs allows computational reasoners to aid in both AOP development and applications. In addition, the incorporation of explicit biological objects will reduce the time required for converting a qualitative AOP description into a conceptual model that can support computational modeling. As high-throughput genomics becomes a more important part of the high-throughput toxicity testing landscape, the new approaches described here for annotating KEs will also promote the visualization and analysis of genomics data in an AOP context.
