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

Johan Nyström-Persson¹, Yayoi Natsume-Kitatani², Yoshinobu Igarashi³

¹Level Five Co., Ltd., GYB Akihabara 3F, 2-25, Kanda-Sudacho, Chiyoda-ku, Tokyo, 101-0041, Japan. johan@level-five.jp.

Scientific Reports

|May 5, 2017

Summary

Toxygates now offers advanced toxicogenomics analysis tools for the Open TG-GATEs database. New features reveal how PPARα agonist WY-14643 causes liver injury via WNT/Ca2+ signaling.

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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.