Rat Deconvolution as Knowledge Miner for Immune Cell Trafficking from Toxicogenomics Databases

Abstract

Toxicogenomics databases are useful for understanding biological responses in individuals because they are derived from well-controlled experiments and include a diverse spectrum of biological responses. Although these database contain no information regarding immune cells in the liver, which are important in the progression of liver injury, deconvolution that estimates cell-type proportions from bulk transcriptome could add information regarding immune cell trafficking to the database. However, deconvolution has been mainly applied to humans and mice and less often to rats, which are the main target of toxicogenomics databases. Here, we developed a deconvolution method for rats and established a methodology to obtain information regarding immune cells from toxicogenomics databases. The contributions of this work are three-fold. First, we obtained the gene expression profiles of various rat immune cells necessary for deconvolution and constructed a dataset; second, we compared the accuracy of models based on human and mouse datasets and showed the impact of species differences on deconvolution; third, we showed that rat deconvolution could retrieve information regarding immune cell trafficking from toxicogenomics databases.

Uncovering the neuroprotective effect of vitamin B12 in pneumococcal meningitis: insights into its pleiotropic mode of action at the transcriptional level

“…Deconvolution analysis of the RNA-Seq data to assess whether PM or adjuvant B12 affect the proportions of major leukocyte types in the inflammatory infiltrate was conducted using the CIBERSORTx software ( 11 ), specifically utilizing the “Impute Cell Fractions” module, and adjusting parameters for batch correction and number of permutations (100). Reference cell type-specific signatures were obtained from validated single-cell RNA-Seq data of rat-derived immune cells available in GitHub (RatDeconvolution) ( 12 ).…”