Nature Nature Genet. 15 June 2003, vol. 34 no. 3 pp 267 ? 273.. Published: 2003.06.14
Vamsi K. Mootha, Cecilia M. Lindgren, Karl-Fredrik Eriksson, Aravind Subramanian, Smita Sihag, Joseph Lehar, Pere Puigserver, Emma Carlsson, Martin Ridderstr?le, Esa Laurila, Nicholas Houstis, Mark J. Daly, Nick Patterson, Jill P. Mesirov, Todd R. Golub, Pablo Tamayo, Bruce Spiegelman, Eric S. Lander, Joel N. Hirschhorn, David Altshuler, and Leif C. Groop
Read ManuscriptDNA 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.
Description | Link/Filename |
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Human diabetes expression data | reannotate_select_cal.eis.gz |
Phenotype data | Phenotype_Data.xls |
Probe sets corresponding to gene sets | all_pathways.tar.gz |
GSEA results for NGT versus DM2 | GSEA_results_NGT_vs_DM2.xls |
OXPHOS homolog expression in mouse | mouse_expression.tar.gz |