PGC-1α-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...
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| Veröffentlicht in: | Nature genetics 2003-07, Vol.34 (3), p.267-273 |
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| container_title | Nature genetics |
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| creator | Mootha, Vamsi K Lindgren, Cecilia M Eriksson, Karl-Fredrik Subramanian, Aravind Sihag, Smita Lehar, Joseph Puigserver, Pere Carlsson, Emma Ridderstråle, 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 |
| 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-1α 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. |
| doi_str_mv | 10.1038/ng1180 |
| format | Article |
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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-1α 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><identifier>ISSN: 1061-4036</identifier><identifier>EISSN: 1546-1718</identifier><identifier>DOI: 10.1038/ng1180</identifier><identifier>CODEN: NGENEC</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Agriculture ; Animal Genetics and Genomics ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; DNA microarrays ; Fundamental and applied biological sciences. Psychology ; Gene Function ; Genetic aspects ; Human Genetics ; Molecular and cellular biology ; Oxidative phosphorylation ; Physiological aspects ; Risk factors ; Type 2 diabetes</subject><ispartof>Nature genetics, 2003-07, Vol.34 (3), p.267-273</ispartof><rights>Springer Nature America, Inc. 2003</rights><rights>2003 INIST-CNRS</rights><rights>COPYRIGHT 2003 Nature Publishing Group</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c449t-13f8101d3b14bb6d3911ff628090733f8b98ad66983d81b98331b507bce59c3b3</citedby><cites>FETCH-LOGICAL-c449t-13f8101d3b14bb6d3911ff628090733f8b98ad66983d81b98331b507bce59c3b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/ng1180$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/ng1180$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14919524$$DView record in Pascal Francis$$Hfree_for_read</backlink></links><search><creatorcontrib>Mootha, Vamsi K</creatorcontrib><creatorcontrib>Lindgren, Cecilia M</creatorcontrib><creatorcontrib>Eriksson, Karl-Fredrik</creatorcontrib><creatorcontrib>Subramanian, Aravind</creatorcontrib><creatorcontrib>Sihag, Smita</creatorcontrib><creatorcontrib>Lehar, Joseph</creatorcontrib><creatorcontrib>Puigserver, Pere</creatorcontrib><creatorcontrib>Carlsson, Emma</creatorcontrib><creatorcontrib>Ridderstråle, Martin</creatorcontrib><creatorcontrib>Laurila, Esa</creatorcontrib><creatorcontrib>Houstis, Nicholas</creatorcontrib><creatorcontrib>Daly, Mark J</creatorcontrib><creatorcontrib>Patterson, Nick</creatorcontrib><creatorcontrib>Mesirov, Jill P</creatorcontrib><creatorcontrib>Golub, Todd R</creatorcontrib><creatorcontrib>Tamayo, Pablo</creatorcontrib><creatorcontrib>Spiegelman, Bruce</creatorcontrib><creatorcontrib>Lander, Eric S</creatorcontrib><creatorcontrib>Hirschhorn, Joel N</creatorcontrib><creatorcontrib>Altshuler, David</creatorcontrib><creatorcontrib>Groop, Leif C</creatorcontrib><title>PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes</title><title>Nature genetics</title><addtitle>Nat Genet</addtitle><description>DNA microarrays can be used to identify gene expression changes characteristic of human disease. 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Psychology</subject><subject>Gene Function</subject><subject>Genetic aspects</subject><subject>Human Genetics</subject><subject>Molecular and cellular biology</subject><subject>Oxidative phosphorylation</subject><subject>Physiological aspects</subject><subject>Risk factors</subject><subject>Type 2 diabetes</subject><issn>1061-4036</issn><issn>1546-1718</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><recordid>eNqNkd9qFDEUxgdRsFZ9hgFR6cXUnE1mNrksi9ZCoeK_25BJzkxTZpM1Z2btPlZfxGcyyyzIihcSQs7J9_sOJF9RvAR2DozLd6EHkOxRcQK1aCpYgnyca9ZAJRhvnhbPiO4YAyGYPCnip8tVBb8eqoS0iYH8FsseA1LpwzYOW3S5KOO9d2bca5vbSHmn3ZD7GEqTsLQxJueDGXHYlS7-DAn7Keuz93Zam1A6b1ockZ4XTzozEL44nKfFtw_vv64-Vtc3l1eri-vKCqHGCngngYHjLYi2bRxXAF3XLCRTbMmz2CppXNMoyZ2E3HAObc2WrcVaWd7y0-LNPHeT4o8JadRrTxaHwQSME2mQEqRQdQZfzWBvBtQ-dHFMxu5hfQGSC1ALuafO_0Hl5XDtbQzY-Xx_ZDg7MmRmxPuxNxORvvry-f_Zm-_H7OFdNkWihJ3eJL82aaeB6X38eo4_g68PH2DImqFLJlhPf2ihQNULkbm3M0dZCj0mfRenFHI2f0_8DRqmurY</recordid><startdate>20030701</startdate><enddate>20030701</enddate><creator>Mootha, Vamsi K</creator><creator>Lindgren, Cecilia M</creator><creator>Eriksson, Karl-Fredrik</creator><creator>Subramanian, Aravind</creator><creator>Sihag, Smita</creator><creator>Lehar, Joseph</creator><creator>Puigserver, Pere</creator><creator>Carlsson, Emma</creator><creator>Ridderstråle, Martin</creator><creator>Laurila, Esa</creator><creator>Houstis, Nicholas</creator><creator>Daly, Mark J</creator><creator>Patterson, Nick</creator><creator>Mesirov, Jill P</creator><creator>Golub, Todd R</creator><creator>Tamayo, Pablo</creator><creator>Spiegelman, Bruce</creator><creator>Lander, Eric S</creator><creator>Hirschhorn, Joel N</creator><creator>Altshuler, David</creator><creator>Groop, Leif C</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><scope>IQODW</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20030701</creationdate><title>PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes</title><author>Mootha, Vamsi K ; Lindgren, Cecilia M ; Eriksson, Karl-Fredrik ; Subramanian, Aravind ; Sihag, Smita ; Lehar, Joseph ; Puigserver, Pere ; Carlsson, Emma ; Ridderstråle, 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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c449t-13f8101d3b14bb6d3911ff628090733f8b98ad66983d81b98331b507bce59c3b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Agriculture</topic><topic>Animal Genetics and Genomics</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>DNA microarrays</topic><topic>Fundamental and applied biological sciences. 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| ispartof | Nature genetics, 2003-07, Vol.34 (3), p.267-273 |
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| source | Springer Nature - Complete Springer Journals; Nature Journals Online |
| subjects | Agriculture Animal Genetics and Genomics Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Research DNA microarrays Fundamental and applied biological sciences. Psychology Gene Function Genetic aspects Human Genetics Molecular and cellular biology Oxidative phosphorylation Physiological aspects Risk factors Type 2 diabetes |
| title | PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes |
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