Introducing WikiPathways as a Data-Source to Support Adverse Outcome Pathways for Regulatory Risk Assessment of Chemicals and Nanomaterials.

Authors:
Marvin Martens
Marvin Martens
Maastricht University
Maastricht | Netherlands
Penny Nymark
Penny Nymark
Finnish Institute of Occupational Health
Finland
Lyle D Burgoon
Lyle D Burgoon
Michigan State University
United States
Hristo Aladjov
Hristo Aladjov
University Prof. As. Zlatarov
Dr Fernando Torres Andón, PhD
Dr Fernando Torres Andón, PhD
University of Santiago de Compostela
AECC Researcher in Nanomedicine for Cancer Immunotherapy
Nanomedicine - Cancer Immunotherapy - Nanotoxicology - Cell Death
Santiago de Compostela, A Coruña | Spain
Chris T Evelo
Chris T Evelo
Maastricht University
Netherlands

Front Genet 2018 21;9:661. Epub 2018 Dec 21.

Department of Bioinformatics - BiGCaT, NUTRIM, Maastricht University, Maastricht, Netherlands.

A paradigm shift is taking place in risk assessment to replace animal models, reduce the number of economic resources, and refine the methodologies to test the growing number of chemicals and nanomaterials. Therefore, approaches such as transcriptomics, proteomics, and metabolomics have become valuable tools in toxicological research, and are finding their way into regulatory toxicity. One promising framework to bridge the gap between the molecular-level measurements and risk assessment is the concept of adverse outcome pathways (AOPs). These pathways comprise mechanistic knowledge and connect biological events from a molecular level toward an adverse effect outcome after exposure to a chemical. However, the implementation of omics-based approaches in the AOPs and their acceptance by the risk assessment community is still a challenge. Because the existing modules in the main repository for AOPs, the AOP Knowledge Base (AOP-KB), do not currently allow the integration of omics technologies, additional tools are required for omics-based data analysis and visualization. Here we show how WikiPathways can serve as a supportive tool to make omics data interoperable with the AOP-Wiki, part of the AOP-KB. Manual matching of key events (KEs) indicated that 67% could be linked with molecular pathways. Automatic connection through linkage of identifiers between the databases showed that only 30% of AOP-Wiki chemicals were found on WikiPathways. More loose linkage through gene names in KE and Key Event Relationships descriptions gave an overlap of 70 and 71%, respectively. This shows many opportunities to create more direct connections, for example with extended ontology annotations, improving its interoperability. This interoperability allows the needed integration of omics data linked to the molecular pathways with AOPs. A new AOP Portal on WikiPathways is presented to allow the community of AOP developers to collaborate and populate the molecular pathways that underlie the KEs of AOP-Wiki. We conclude that the integration of WikiPathways and AOP-Wiki will improve risk assessment because omics data will be linked directly to KEs and therefore allow the comprehensive understanding and description of AOPs. To make this assessment reproducible and valid, major changes are needed in both WikiPathways and AOP-Wiki.

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Source
http://dx.doi.org/10.3389/fgene.2018.00661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6308971PMC

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December 2018
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