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Title:
PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes | Nature Genetics
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.
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name:Aravind Subramanian
affiliation:
name:Whitehead Institute/MIT Center for Genome Research
address:
name:Whitehead Institute/MIT Center for Genome Research, Cambridge, USA
type:PostalAddress
type:Organization
name:Smita Sihag
affiliation:
name:Whitehead Institute/MIT Center for Genome Research
address:
name:Whitehead Institute/MIT Center for Genome Research, Cambridge, USA
type:PostalAddress
type:Organization
name:Joseph Lehar
affiliation:
name:Whitehead Institute/MIT Center for Genome Research
address:
name:Whitehead Institute/MIT Center for Genome Research, Cambridge, USA
type:PostalAddress
type:Organization
name:Pere Puigserver
affiliation:
name:Dana Farber Cancer Institute, Harvard Medical School
address:
name:Dana Farber Cancer Institute, Harvard Medical School, Boston, USA
type:PostalAddress
type:Organization
name:Emma Carlsson
affiliation:
name:Wallenberg Laboratory, University Hospital MAS, Lund University
address:
name:Department of Endocrinology, Wallenberg Laboratory, University Hospital MAS, Lund University, Malmo, Sweden
type:PostalAddress
type:Organization
name:Martin Ridderstråle
affiliation:
name:Wallenberg Laboratory, University Hospital MAS, Lund University
address:
name:Department of Endocrinology, Wallenberg Laboratory, University Hospital MAS, Lund University, Malmo, Sweden
type:PostalAddress
type:Organization
name:Esa Laurila
affiliation:
name:Wallenberg Laboratory, University Hospital MAS, Lund University
address:
name:Department of Endocrinology, Wallenberg Laboratory, University Hospital MAS, Lund University, Malmo, Sweden
type:PostalAddress
type:Organization
name:Nicholas Houstis
affiliation:
name:Whitehead Institute/MIT Center for Genome Research
address:
name:Whitehead Institute/MIT Center for Genome Research, Cambridge, USA
type:PostalAddress
type:Organization
name:Mark J Daly
affiliation:
name:Whitehead Institute/MIT Center for Genome Research
address:
name:Whitehead Institute/MIT Center for Genome Research, Cambridge, USA
type:PostalAddress
type:Organization
name:Nick Patterson
affiliation:
name:Whitehead Institute/MIT Center for Genome Research
address:
name:Whitehead Institute/MIT Center for Genome Research, Cambridge, USA
type:PostalAddress
type:Organization
name:Jill P Mesirov
affiliation:
name:Whitehead Institute/MIT Center for Genome Research
address:
name:Whitehead Institute/MIT Center for Genome Research, Cambridge, USA
type:PostalAddress
type:Organization
name:Todd R Golub
affiliation:
name:Whitehead Institute/MIT Center for Genome Research
address:
name:Whitehead Institute/MIT Center for Genome Research, Cambridge, USA
type:PostalAddress
type:Organization
name:Dana Farber Cancer Institute, Harvard Medical School
address:
name:Dana Farber Cancer Institute, Harvard Medical School, Boston, USA
type:PostalAddress
type:Organization
name:Pablo Tamayo
affiliation:
name:Whitehead Institute/MIT Center for Genome Research
address:
name:Whitehead Institute/MIT Center for Genome Research, Cambridge, USA
type:PostalAddress
type:Organization
name:Bruce Spiegelman
affiliation:
name:Dana Farber Cancer Institute, Harvard Medical School
address:
name:Dana Farber Cancer Institute, Harvard Medical School, Boston, USA
type:PostalAddress
type:Organization
name:Eric S Lander
affiliation:
name:Whitehead Institute/MIT Center for Genome Research
address:
name:Whitehead Institute/MIT Center for Genome Research, Cambridge, USA
type:PostalAddress
type:Organization
name:Massachusetts Institute of Technology
address:
name:Department of Biology, Massachusetts Institute of Technology, Cambridge, USA
type:PostalAddress
type:Organization
name:Joel N Hirschhorn
affiliation:
name:Whitehead Institute/MIT Center for Genome Research
address:
name:Whitehead Institute/MIT Center for Genome Research, Cambridge, USA
type:PostalAddress
type:Organization
name:Harvard Medical School
address:
name:Department of Genetics, Harvard Medical School, Boston, USA
type:PostalAddress
type:Organization
name:Children's Hospital
address:
name:Divisions of Pediatrics and Endocrinology, Children's Hospital, Boston, USA
type:PostalAddress
type:Organization
name:David Altshuler
affiliation:
name:Whitehead Institute/MIT Center for Genome Research
address:
name:Whitehead Institute/MIT Center for Genome Research, Cambridge, USA
type:PostalAddress
type:Organization
name:Harvard Medical School
address:
name:Department of Medicine, Harvard Medical School, Boston, USA
type:PostalAddress
type:Organization
name:Harvard Medical School
address:
name:Department of Genetics, Harvard Medical School, Boston, USA
type:PostalAddress
type:Organization
name:Massachusetts General Hospital
address:
name:Department of Molecular Biology and Diabetes Unit, Massachusetts General Hospital, Boston, USA
type:PostalAddress
type:Organization
email:[email protected]
name:Leif C Groop
affiliation:
name:Wallenberg Laboratory, University Hospital MAS, Lund University
address:
name:Department of Endocrinology, Wallenberg Laboratory, University Hospital MAS, Lund University, Malmo, Sweden
type:PostalAddress
type:Organization
email:[email protected]
PostalAddress:
name:Whitehead Institute/MIT Center for Genome Research, Cambridge, USA
name:Department of Medicine, Harvard Medical School, Boston, USA
name:Department of Medicine, Brigham and Women's Hospital, Boston, USA
name:Whitehead Institute/MIT Center for Genome Research, Cambridge, USA
name:Department of Endocrinology, Wallenberg Laboratory, University Hospital MAS, Lund University, Malmo, Sweden
name:Department of Endocrinology, Wallenberg Laboratory, University Hospital MAS, Lund University, Malmo, Sweden
name:Whitehead Institute/MIT Center for Genome Research, Cambridge, USA
name:Whitehead Institute/MIT Center for Genome Research, Cambridge, USA
name:Whitehead Institute/MIT Center for Genome Research, Cambridge, USA
name:Dana Farber Cancer Institute, Harvard Medical School, Boston, USA
name:Department of Endocrinology, Wallenberg Laboratory, University Hospital MAS, Lund University, Malmo, Sweden
name:Department of Endocrinology, Wallenberg Laboratory, University Hospital MAS, Lund University, Malmo, Sweden
name:Department of Endocrinology, Wallenberg Laboratory, University Hospital MAS, Lund University, Malmo, Sweden
name:Whitehead Institute/MIT Center for Genome Research, Cambridge, USA
name:Whitehead Institute/MIT Center for Genome Research, Cambridge, USA
name:Whitehead Institute/MIT Center for Genome Research, Cambridge, USA
name:Whitehead Institute/MIT Center for Genome Research, Cambridge, USA
name:Whitehead Institute/MIT Center for Genome Research, Cambridge, USA
name:Dana Farber Cancer Institute, Harvard Medical School, Boston, USA
name:Whitehead Institute/MIT Center for Genome Research, Cambridge, USA
name:Dana Farber Cancer Institute, Harvard Medical School, Boston, USA
name:Whitehead Institute/MIT Center for Genome Research, Cambridge, USA
name:Department of Biology, Massachusetts Institute of Technology, Cambridge, USA
name:Whitehead Institute/MIT Center for Genome Research, Cambridge, USA
name:Department of Genetics, Harvard Medical School, Boston, USA
name:Divisions of Pediatrics and Endocrinology, Children's Hospital, Boston, USA
name:Whitehead Institute/MIT Center for Genome Research, Cambridge, USA
name:Department of Medicine, Harvard Medical School, Boston, USA
name:Department of Genetics, Harvard Medical School, Boston, USA
name:Department of Molecular Biology and Diabetes Unit, Massachusetts General Hospital, Boston, USA
name:Department of Endocrinology, Wallenberg Laboratory, University Hospital MAS, Lund University, Malmo, Sweden
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