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

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 databases 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. Correspondence: Tadahaya Mizuno To establish and validate a rat-specific deconvolution, RNA-sequencing analysis was performed on 6 types of sorted immune cells obtained from the spleen and the blood, the whole blood cells, the spleen, and the liver of rats.