PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes.
DNA microarrays can be used to identify 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 coord...
Main Authors: | , , , , , , , , , , , , , , , , , , , , |
---|---|
Format: | Journal article |
Language: | English |
Published: |
2003
|
_version_ | 1797103451029635072 |
---|---|
author | Mootha, V Lindgren, C Eriksson, K Subramanian, A Sihag, S Lehar, J Puigserver, P Carlsson, E Ridderstråle, M Laurila, E Houstis, N Daly, M Patterson, N Mesirov, J Golub, T Tamayo, P Spiegelman, B Lander, E Hirschhorn, J Altshuler, D Groop, L |
author_facet | Mootha, V Lindgren, C Eriksson, K Subramanian, A Sihag, S Lehar, J Puigserver, P Carlsson, E Ridderstråle, M Laurila, E Houstis, N Daly, M Patterson, N Mesirov, J Golub, T Tamayo, P Spiegelman, B Lander, E Hirschhorn, J Altshuler, D Groop, L |
author_sort | Mootha, V |
collection | OXFORD |
description | DNA microarrays can be used to identify 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-1alpha 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. |
first_indexed | 2024-03-07T06:20:17Z |
format | Journal article |
id | oxford-uuid:f27ec269-f99d-4420-9aee-d23dd78f3904 |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T06:20:17Z |
publishDate | 2003 |
record_format | dspace |
spelling | oxford-uuid:f27ec269-f99d-4420-9aee-d23dd78f39042022-03-27T12:04:15ZPGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f27ec269-f99d-4420-9aee-d23dd78f3904EnglishSymplectic Elements at Oxford2003Mootha, VLindgren, CEriksson, KSubramanian, ASihag, SLehar, JPuigserver, PCarlsson, ERidderstråle, MLaurila, EHoustis, NDaly, MPatterson, NMesirov, JGolub, TTamayo, PSpiegelman, BLander, EHirschhorn, JAltshuler, DGroop, LDNA microarrays can be used to identify 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-1alpha 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. |
spellingShingle | Mootha, V Lindgren, C Eriksson, K Subramanian, A Sihag, S Lehar, J Puigserver, P Carlsson, E Ridderstråle, M Laurila, E Houstis, N Daly, M Patterson, N Mesirov, J Golub, T Tamayo, P Spiegelman, B Lander, E Hirschhorn, J Altshuler, D Groop, L PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. |
title | PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. |
title_full | PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. |
title_fullStr | PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. |
title_full_unstemmed | PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. |
title_short | PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. |
title_sort | pgc 1alpha responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes |
work_keys_str_mv | AT moothav pgc1alpharesponsivegenesinvolvedinoxidativephosphorylationarecoordinatelydownregulatedinhumandiabetes AT lindgrenc pgc1alpharesponsivegenesinvolvedinoxidativephosphorylationarecoordinatelydownregulatedinhumandiabetes AT erikssonk pgc1alpharesponsivegenesinvolvedinoxidativephosphorylationarecoordinatelydownregulatedinhumandiabetes AT subramaniana pgc1alpharesponsivegenesinvolvedinoxidativephosphorylationarecoordinatelydownregulatedinhumandiabetes AT sihags pgc1alpharesponsivegenesinvolvedinoxidativephosphorylationarecoordinatelydownregulatedinhumandiabetes AT leharj pgc1alpharesponsivegenesinvolvedinoxidativephosphorylationarecoordinatelydownregulatedinhumandiabetes AT puigserverp pgc1alpharesponsivegenesinvolvedinoxidativephosphorylationarecoordinatelydownregulatedinhumandiabetes AT carlssone pgc1alpharesponsivegenesinvolvedinoxidativephosphorylationarecoordinatelydownregulatedinhumandiabetes AT ridderstralem pgc1alpharesponsivegenesinvolvedinoxidativephosphorylationarecoordinatelydownregulatedinhumandiabetes AT laurilae pgc1alpharesponsivegenesinvolvedinoxidativephosphorylationarecoordinatelydownregulatedinhumandiabetes AT houstisn pgc1alpharesponsivegenesinvolvedinoxidativephosphorylationarecoordinatelydownregulatedinhumandiabetes AT dalym pgc1alpharesponsivegenesinvolvedinoxidativephosphorylationarecoordinatelydownregulatedinhumandiabetes AT pattersonn pgc1alpharesponsivegenesinvolvedinoxidativephosphorylationarecoordinatelydownregulatedinhumandiabetes AT mesirovj pgc1alpharesponsivegenesinvolvedinoxidativephosphorylationarecoordinatelydownregulatedinhumandiabetes AT golubt pgc1alpharesponsivegenesinvolvedinoxidativephosphorylationarecoordinatelydownregulatedinhumandiabetes AT tamayop pgc1alpharesponsivegenesinvolvedinoxidativephosphorylationarecoordinatelydownregulatedinhumandiabetes AT spiegelmanb pgc1alpharesponsivegenesinvolvedinoxidativephosphorylationarecoordinatelydownregulatedinhumandiabetes AT landere pgc1alpharesponsivegenesinvolvedinoxidativephosphorylationarecoordinatelydownregulatedinhumandiabetes AT hirschhornj pgc1alpharesponsivegenesinvolvedinoxidativephosphorylationarecoordinatelydownregulatedinhumandiabetes AT altshulerd pgc1alpharesponsivegenesinvolvedinoxidativephosphorylationarecoordinatelydownregulatedinhumandiabetes AT groopl pgc1alpharesponsivegenesinvolvedinoxidativephosphorylationarecoordinatelydownregulatedinhumandiabetes |