Interactive Toxicogenomics: Gene set discovery, clustering and analysis in Toxygates

Area of Science:

• Toxicology
• Bioinformatics
• Genomics

Background:

• The Open TG-GATEs database provides large-scale toxicogenomics data.
• Toxygates enhances accessibility and analysis of this toxicogenomics data.
• Previous versions lacked advanced computational analysis features.

Purpose of the Study:

• To introduce new functionalities in Toxygates for sophisticated toxicogenomics analysis.
• To enable users with limited bioinformatics skills to analyze toxicogenomics data.
• To investigate the hepatotoxicity mechanism of WY-14643 using the enhanced Toxygates platform.

Main Methods:

• Implemented orthologous mode for cross-species data comparison.
• Integrated interactive clustering and heatmap visualization.
• Added gene set enrichment analysis and user data uploading capabilities.
• Utilized Toxygates to study the effects of PPARα agonist WY-14643.

Main Results:

• WY-14643 induced hepatotoxicity, specifically hypertrophy in the bile duct.
• Intracellular calcium (Ca2+) dysregulation was identified as a key mechanism.
• The study revealed induction of genes within a non-canonical WNT/Ca2+ signaling pathway.
• Demonstrated the utility of enhanced Toxygates for in-depth toxicogenomics analysis.

Conclusions:

• The enhanced Toxygates platform provides powerful tools for toxicogenomics research.
• WY-14643-induced hepatotoxicity involves disruption of cellular signaling pathways.
• Toxygates facilitates comprehensive analysis of both Open TG-GATEs and user-uploaded datasets.