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Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
Published on: January 31, 2022
TOXPANEL: A Gene-Set Analysis Tool to Assess Liver and Kidney Injuries
Patric Schyman1,2, Zhen Xu1,2, Valmik Desai1,2
1DoD Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Development Command, Fort Detrick, MD, United States.
Abstract:
Gene-set analysis is commonly used to identify trends in gene expression when cells, tissues, organs, or organisms are subjected to conditions that differ from those within the normal physiological range. However, tools for gene-set analysis to assess liver and kidney injury responses are less common. Furthermore, most websites for gene-set analysis lack the option for users to customize their gene-set database. Here, we present the ToxPanel website, which allows users to perform gene-set analysis to assess liver and kidney injuries using activation scores based on gene-expression fold-change values. The results are graphically presented to assess constituent injury phenotypes (histopathology), with interactive result tables that identify the main contributing genes to a given signal. In addition, ToxPanel offers the flexibility to analyze any set of custom genes based on gene fold-change values. ToxPanel is publically available online at https://toxpanel.bhsai.org. ToxPanel allows users to access our previously developed liver and kidney injury gene sets, which we have shown in previous work to yield robust results that correlate with the degree of injury. Users can also test and validate their customized gene sets using the ToxPanel website.
Insights
ToxPanel is a new website for gene-set analysis of liver and kidney injury. It allows users to analyze custom gene sets and visualize results, aiding toxicological research.
Area of Science:
- Toxicology and Bioinformatics
- Computational Biology
- Genomics
Background:
- Gene-set analysis is crucial for understanding gene expression changes in response to physiological stress.
- Existing tools for analyzing liver and kidney injury responses are limited.
- Many gene-set analysis platforms lack user-defined database customization.
Purpose of the Study:
- To introduce ToxPanel, a novel web-based platform for gene-set analysis focused on liver and kidney injury.
- To provide a user-friendly tool for assessing toxicological responses using gene expression data.
- To enable customized gene-set analysis for broader toxicological applications.
Main Methods:
- Development of the ToxPanel website (https://toxpanel.bhsai.org).
- Implementation of gene-set analysis using activation scores based on gene-expression fold-change values.
- Graphical presentation of results for injury phenotypes and interactive tables for key gene identification.
- Inclusion of pre-established liver and kidney injury gene sets and functionality for custom gene set analysis.
Main Results:
- ToxPanel enables gene-set analysis for liver and kidney injuries.
- The platform provides graphical and interactive visualizations of gene expression trends.
- Users can leverage pre-existing gene sets or upload and analyze custom gene sets.
- Results demonstrate correlation with injury severity, validating the approach.
Conclusions:
- ToxPanel offers a flexible and accessible tool for toxicological gene-set analysis.
- The website facilitates the identification of injury-related gene expression patterns.
- ToxPanel supports both predefined and custom gene sets, enhancing its utility in research.
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