E-CBIL-30 - Transcription profiling of human skeletal muscle from males with type 2 diabetes to identify genes involved in oxidative phosphorylation
Released on 17 July 2007, last updated on 12 October 2011
DNA microarrays can be used to discover gene expression changes characteristic of human disease. This is challenging, however, when relevant differences are subtle at the level of individual genes. We introduce an analytical strategy, Gene Set Enrichment Analysis, designed to detect modest but coordinate changes in the expression of groups of functionally related genes. Using this approach, we identify a set of genes involved in oxidative phosphorylation whose expression is coordinately decreased in human diabetic muscle. Expression of these genes is high at sites of insulin-mediated glucose disposal, activated by PGC-1a, and correlated with total-body aerobic capacity. Our results associate this gene set with clinically important variation in human metabolism, and illustrate the value of pathway relationships in the analysis of genomic profiling experiments.
transcription profiling by array, disease state
Disease and phenotype gene set analysis of disease-based gene expression in mouse and human. De S, Zhang Y, Garner JR, Wang SA, Becker KG. :162-167 (2010), PMID:20682848
PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Mootha Vamsi K, Lindgren Cecilia M, Eriksson Karl-Fredrik, Subramanian Aravind, Sihag Smita, Lehar Joseph, Puigserver Pere, Carlsson Emma, Ridderstrale Martin, Laurila Esa, Houstis Nicholas, Daly Mark J, Patterson Nick, Mesirov Jill P, Golub Todd R, Tamayo Pablo, Spiegelman Bruce, Lander Eric S, Hirschhorn Joel N, Altshuler David, Groop Leif C.