Concordant and discordant gene expression patterns in mouse strains identify best-fit animal model for human tuberculosis

Abstract

Immunity in infection, inflammation and malignancy differs markedly in man and mouse. Still, we learn about human immunity in large extent from experimental mouse models. We propose a novel data integration approach which identifies concordant and discordant gene expression patterns of the immune responses in heterologous data sets. We have conducted experiments to compare human and murine transcriptional responses to Mycobacterium tuberculosis (Mtb) infection in whole blood (WB) as well as macrophages and compared them with simulated as well as publicly available data. Our results indicate profound differences between patterns of gene expression in innate and adaptive immunity in man and mouse upon Mtb infection. We characterized differential expression of T-cell related genes corresponding to the differences in phenotype between tuberculosis (TB) highly and low susceptible mouse strains. Our approach is general and facilitates the choice of optimal animal model for studies of the human immune response to a particular disease.