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.

Highlights

  • TOXPANEL is a web-based tool to assess liver and kidney injury from in vitro or in vivo genomic data

  • With the use of TG-GATE, we identified common gene responses that correlated with the severity of injury, including fibrosis, using in silico approaches

  • We have shown that the combination of our modular approach to identify key injury phenotype together with pathway analysis, provided in ToxPanel, can be useful when understanding the underlying molecular mechanisms in e.g., liver or kidney injury (Schyman et al, 2020a; Schyman et al, 2020b)

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Summary

INTRODUCTION

TOXPANEL is a web-based tool to assess liver and kidney injury from in vitro or in vivo genomic data. We previously derived 11 liver- and 8 kidney-injury modules (Te et al, 2016) from the Open Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System (TG-GATEs) database (Igarashi et al, 2015), where each injury module is uniquely associated with a specific organ-injury phenotype, see Table 1. The TG-GATEs database contains gene-expression data from Sprague Dawley rats exposed to different chemicals for 4–29 days with corresponding documented and graded histopathological injury phenotypes. With the use of TG-GATE, we identified common gene responses (injury modules) that correlated with the severity of injury, including fibrosis, using in silico approaches.

A Web-Tool for Predictive Toxicology
METHODS
RESULTS AND DISCUSSION
DATA AVAILABILITY STATEMENT
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