Independent component analysis of gene expression profiles in the hepatic inflammatory response

Abstract

The response of the liver to inflammatory cues involves a complex interplay by which input signals from the circulation are translated into outputs in the form of differential gene and protein expression, resulting in the diversion of metabolic and synthetic machinery from the normal state to one that is focused on host defense. We seek to understand better the molecular programs (sources) driving these changes in order to better control adverse effects of the inflammatory response without compromising its beneficial aspects. To this end, we have used independent component analysis (ICA) of gene expression profiles obtained from both in vivo and in vitro models of the hepatic acute phase response. We have found that the most significant sources obtained from ICA analysis clustered the profiles into groups of genes with common molecular function. The comparison of in vitro and in vivo modes of gene expression shows both conserved and stimulus-specific programs within the overall inflammatory response.