Journal ArticleDOI
PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes
Vamsi K. Mootha,Cecilia M. Lindgren,Cecilia M. Lindgren,Karl-Fredrik Eriksson,Aravind Subramanian,Smita Sihag,J. Lehar,Pere Puigserver,Emma Carlsson,Martin Ridderstråle,Esa Laurila,Nicholas E. Houstis,Mark J. Daly,Nick Patterson,Jill P. Mesirov,Todd R. Golub,Todd R. Golub,Pablo Tamayo,Bruce M. Spiegelman,Eric S. Lander,Joel N. Hirschhorn,Joel N. Hirschhorn,Joel N. Hirschhorn,David Altshuler,Leif Groop +24 more
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TLDR
An analytical strategy is introduced, Gene Set Enrichment Analysis, designed to detect modest but coordinate changes in the expression of groups of functionally related genes, which identifies a set of genes involved in oxidative phosphorylation whose expression is coordinately decreased in human diabetic muscle.Abstract:
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.read more
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The role of aberrant mitochondrial bioenergetics in diabetic neuropathy.
TL;DR: The role of mitochondrial dysfunction in the etiology of diabetic neuropathy is compared with other types of neuropathy with a distal dying-back pathology such as Friedreich ataxia, Charcot-Marie-Tooth disease type 2 and human immunodeficiency virus-associated distal-symmetric neuropathy.
Journal ArticleDOI
Cardiovascular Networks Systems-Based Approaches to Cardiovascular Disease
Aldons J. Lusis,James N. Weiss +1 more
TL;DR: A new branch of biology, called systems biology, seeks to identify the components of complex systems and to model their dynamic interactions, arose in large part as a result of new technical and analytical developments.
Journal ArticleDOI
Transcriptional and functional profiling defines human small intestinal macrophage subsets.
Anna Bujko,Nader Atlasy,Ole J. B. Landsverk,Lisa Richter,Sheraz Yaqub,Rune Horneland,Ole Øyen,Einar Martin Aandahl,Einar Martin Aandahl,Lars Aabakken,Hendrik G. Stunnenberg,Espen S. Baekkevold,Frode L. Jahnsen +12 more
TL;DR: Assessment of their turnover in duodenal transplants revealed that all Mf subsets were completely replaced over time; Mf1 and Mf2, phenotypically similar to peripheral blood monocytes (PBMos), were largely replaced within 3 wk, whereas two subsets with features of mature Mfs, Mf3 and M f4, exhibited significantly slower replacement.
Journal ArticleDOI
Insulin-resistant muscle is exercise resistant: Evidence for reduced response of nuclear-encoded mitochondrial genes to exercise
Elena A. De Filippis,Guy Alvarez,Rachele Berria,Kenneth Cusi,Sarah Everman,Christian Meyer,Lawrence J. Mandarino +6 more
TL;DR: Investigating whether a bout of exercise induces the same increase in nuclear-encoded mitochondrial gene expression in insulin-sensitive and insulin-resistant subjects matched for exercise capacity found there was a delayed and reduced response in PGC-1alpha mRNA and protein, and phosphorylation of AMP-dependent protein kinase was transient.
Journal ArticleDOI
Skeletal muscle and plasma lipidomic signatures of insulin resistance and overweight/obesity in humans
Katherine T. Tonks,Adelle C.F. Coster,Adelle C.F. Coster,Michael J. Christopher,Rima Chaudhuri,A Xu,Johann A. Gagnon-Bartsch,Donald J. Chisholm,Donald J. Chisholm,David E. James,Peter J. Meikle,Dorit Samocha-Bonet,Dorit Samocha-Bonet +12 more
TL;DR: Alterations in lipids in muscle and plasma have been documented in insulin‐resistant people with obesity and whether these lipid alterations are a reflection of insulin resistance or obesity remains unclear.
References
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Journal ArticleDOI
Cluster analysis and display of genome-wide expression patterns
TL;DR: A system of cluster analysis for genome-wide expression data from DNA microarray hybridization is described that uses standard statistical algorithms to arrange genes according to similarity in pattern of gene expression, finding in the budding yeast Saccharomyces cerevisiae that clustering gene expression data groups together efficiently genes of known similar function.
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Molecular classification of cancer: class discovery and class prediction by gene expression monitoring.
Todd R. Golub,Todd R. Golub,Donna K. Slonim,Pablo Tamayo,Christine Huard,Michelle Gaasenbeek,Jill P. Mesirov,Hilary A. Coller,Mignon L. Loh,James R. Downing,Michael A. Caligiuri,Clara D. Bloomfield,Eric S. Lander +12 more
TL;DR: A generic approach to cancer classification based on gene expression monitoring by DNA microarrays is described and applied to human acute leukemias as a test case and suggests a general strategy for discovering and predicting cancer classes for other types of cancer, independent of previous biological knowledge.
Journal ArticleDOI
Significance analysis of microarrays applied to the ionizing radiation response
TL;DR: A method that assigns a score to each gene on the basis of change in gene expression relative to the standard deviation of repeated measurements is described, suggesting that this repair pathway for UV-damaged DNA might play a previously unrecognized role in repairing DNA damaged by ionizing radiation.
Journal ArticleDOI
A direct approach to false discovery rates
TL;DR: The calculation of the q‐value is discussed, the pFDR analogue of the p‐value, which eliminates the need to set the error rate beforehand as is traditionally done, and can yield an increase of over eight times in power compared with the Benjamini–Hochberg FDR method.
Journal ArticleDOI
Mechanisms Controlling Mitochondrial Biogenesis and Respiration through the Thermogenic Coactivator PGC-1
Zhidan Wu,Pere Puigserver,Ulf Andersson,Chen-Yu Zhang,Guillaume Adelmant,Vamsi K. Mootha,Amy E Troy,Saverio Cinti,Bradford B. Lowell,Richard C. Scarpulla,Bruce M. Spiegelman +10 more
TL;DR: PGC-1, a cold-inducible coactivator of nuclear receptors, stimulates mitochondrial biogenesis and respiration in muscle cells through an induction of uncoupling protein 2 (UCP-2) and through regulation of the nuclear respiratory factors (NRFs).
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