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

Area of Science:

• Toxicology and Risk Assessment
• Bioinformatics and Computational Biology
• Molecular Biology

Background:

• The field of toxicology is shifting towards non-animal testing methods, utilizing 'omics' technologies like transcriptomics, proteomics, and metabolomics.
• Adverse Outcome Pathways (AOPs) provide a framework to connect molecular initiating events to adverse health outcomes, but integrating 'omics' data remains a challenge.
• Current AOP Knowledge Base (AOP-KB) lacks direct support for 'omics' data integration, hindering comprehensive toxicological assessments.

Purpose of the Study:

• To demonstrate how WikiPathways can enhance the interoperability of 'omics' data with the AOP-Wiki for improved risk assessment.
• To present a new AOP Portal on WikiPathways for collaborative development of molecular pathways underlying AOP key events.
• To facilitate the integration of 'omics' data directly linked to AOP key events for a more robust understanding of chemical toxicity.

Main Methods:

• Manual and automatic linkage of data between WikiPathways and AOP-Wiki, including chemical identifiers and gene names.
• Analysis of overlap percentages between AOP-Wiki chemicals and pathways in WikiPathways.
• Development of an AOP Portal on WikiPathways to support community collaboration.

Main Results:

• Manual matching linked 67% of AOP key events to molecular pathways.
• Automatic identifier linkage found only 30% overlap between AOP-Wiki chemicals and WikiPathways.
• Gene name linkage showed higher overlap (70-71%), indicating opportunities for improved interoperability via ontology annotations.

Conclusions:

• Integrating WikiPathways with AOP-Wiki significantly improves risk assessment by directly linking 'omics' data to AOP key events.
• The developed AOP Portal fosters collaboration and populates molecular pathways crucial for AOP understanding.
• Enhanced interoperability between these platforms is essential for reproducible and valid toxicological assessments, requiring further development in both systems.