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
Citations
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Journal ArticleDOI
Comparative evaluation of gene-set analysis methods
TL;DR: While the three methods showed similar power using permutation inference after a proper standardization of gene expression data, SAM-GS showed slightly higher power than the Global Tests, which makes the performance of all three methods similar, given the use of permutation-based inference.
Book ChapterDOI
Insulin Resistance and Mitochondrial Dysfunction
TL;DR: The evidence linking mitochondrial dysfunction and insulin resistance is presented, the potential for mitochondrial targets as a therapeutic approach for T2D is reviewed, and the evidence linking insulin resistance and mitochondrial dysfunction is presented.
Journal ArticleDOI
Unite and conquer
TL;DR: This article compares the performance of univariate and multivariate tests on both simulated and biological data and demonstrates that due to complementing null hypotheses each test projects on different aspects of the data and for the analysis of biological data it is beneficial to use all three tests simultaneously instead of focusing exclusively on just one.
Journal ArticleDOI
The genetic regulatory signature of type 2 diabetes in human skeletal muscle
Laura J. Scott,Michael R. Erdos,Jeroen R. Huyghe,Ryan P. Welch,Andrew T. Beck,Brooke N. Wolford,Peter S. Chines,John P. Didion,Narisu Narisu,Heather M. Stringham,D. Leland Taylor,D. Leland Taylor,Anne U. Jackson,Swarooparani Vadlamudi,Lori L. Bonnycastle,Leena Kinnunen,Jouko Saramies,Jouko Sundvall,Ricardo D’Oliveira Albanus,Anna Kiseleva,John Hensley,Gregory E. Crawford,Hui Jiang,Xiaoquan Wen,Richard M. Watanabe,Timo A. Lakka,Karen L. Mohlke,Markku Laakso,Jaakko Tuomilehto,Heikki A. Koistinen,Heikki A. Koistinen,Heikki A. Koistinen,Michael Boehnke,Francis S. Collins,Stephen C. J. Parker +34 more
TL;DR: In this article, the authors analyse skeletal muscle biopsies from 271 well-phenotyped Finnish participants with glucose tolerance ranging from normal to newly diagnosed Type 2 diabetes (T2D) to understand how T2D status, metabolic traits and genetic variation influence gene expression.
Journal ArticleDOI
Proteomic profiling of extracellular vesicles allows for human breast cancer subtyping
Stamatia Rontogianni,Eleni Synadaki,Bohui Li,Marte C. Liefaard,Esther H. Lips,Jelle Wesseling,Wei Wu,Maarten Altelaar,Maarten Altelaar +8 more
TL;DR: It is shown that the proteomic profiles of extracellular vesicles secreted by different classes of breast cancer cell lines can be used as biomarkers of their respective subtype and provide molecular evidence for subtype-specific biological processes and pathways.
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.
Journal ArticleDOI
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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