Gene Expression Reactomes Across Species Do Not Correlate with Gene Structural Similarity

Mammalian animal model species for preclinical drug testing share a large number of genes with similar names and/or protein primary structures, but gene expression patterns in different tissues and in response to different drugs have not been previously systematically characterized. Here, we experimentally measure the gene expression responses (reactomes) of each gene in the mouse and rat genomes in 10 different organs to 3 different drugs. Surprisingly, we observe that gene reactomes across species generally do not correlate with structural similarity. Thus, we propose an alternative functional cross-species gene mapping approach, based on organ-specific gene expression response to drug dosing. ### Competing Interest Statement D.Y.Z. declares competing interest in the form of significant equity ownership in Pupil Bio and NuProbe Global. A.G. declares competing interest in the form of consulting for and significant equity interest in Iuno and Argome. All other authors have no other competing interests.