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Rat deconvolution as knowledge miner for immune cell trafficking from toxicogenomics databases.

Katsuhisa Morita1, Tadahaya Mizuno1, Iori Azuma1

  • 1Department of Pharmaceutical Sciences, The University of Tokyo, Bunkyo, Tokyo, Japan.

Toxicological Sciences : an Official Journal of the Society of Toxicology
|November 9, 2023
PubMed
Summary

We developed a rat-specific deconvolution method to analyze immune cell trafficking in toxicogenomics databases, revealing new insights into liver injury and compound responses.

Keywords:
deconvolutionimmune cellrattoxicogenomicstranscriptome

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Area of Science:

  • Toxicology
  • Immunology
  • Bioinformatics

Background:

  • Toxicogenomics databases offer broad biological response data but lack immune cell information crucial for liver injury.
  • Deconvolution methods, primarily for human/mouse, can estimate cell proportions from transcriptomes.
  • Rats are key in toxicogenomics, yet deconvolution methods for them are underdeveloped.

Purpose of the Study:

  • To develop and validate a rat-specific deconvolution method for extracting immune cell information from toxicogenomics databases.
  • To investigate the impact of species differences on deconvolution accuracy.
  • To identify compound clusters based on immune cell trafficking patterns.

Main Methods:

  • Developed a novel rat-specific deconvolution algorithm.
  • Generated gene expression profiles for 6 key rat immune cell types.
  • Applied the method to the Open TG-GATEs toxicogenomics database.
  • Compared rat deconvolution results with human and mouse data.

Main Results:

  • Rat-specific deconvolution demonstrated high correlations for immune cell types in spleen, blood, and toxicant-treated liver.
  • Significant differences were observed in deconvolution accuracy across species.
  • Identified 4 distinct compound clusters based on estimated immune cell trafficking, differing from transcriptome-only classifications.

Conclusions:

  • The developed rat deconvolution method effectively retrieves immune cell trafficking data from toxicogenomics databases.
  • Species-specific approaches are critical for accurate deconvolution in toxicological studies.
  • This work enables deeper understanding of immune cell roles in pathologies and supports Adverse Outcome Pathway evaluations.