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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DNA methylation profiling reveals a predominant immune component in breast cancers.
Sarah Dedeurwaerder,Christine Desmedt,Emilie Calonne,Sandeep Singhal,Benjamin Haibe-Kains,Matthieu Defrance,Stefan Michiels,Michael Volkmar,Rachel Deplus,Judith Luciani,Françoise Lallemand,Denis Larsimont,Jérôme Toussaint,Sandy Haussy,Françoise Rothé,Ghizlane Rouas,Otto Metzger,Samira Majjaj,Kamal S Saini,Pascale Putmans,Gérald Hames,Nicolas van Baren,Pierre Coulie,Martine Piccart,Christos Sotiriou,François Fuks +25 more
TL;DR: The immune component uncovered here by DNA methylation profiles provides a new perspective for the importance of the microenvironment in breast cancer, holding implications for better management of breast cancer patients.
Journal ArticleDOI
Evidence for Polygenic Adaptation to Pathogens in the Human Genome
Josephine T. Daub,Tamara Hofer,Tamara Hofer,Emilie Cutivet,Isabelle Dupanloup,Isabelle Dupanloup,Lluis Quintana-Murci,Lluis Quintana-Murci,Marc Robinson-Rechavi,Marc Robinson-Rechavi,Laurent Excoffier,Laurent Excoffier +11 more
TL;DR: The results show that past interactions with pathogens have elicited widespread and coordinated genomic responses, and suggest that adaptation to pathogens can be considered as a primary example of polygenic selection.
Journal ArticleDOI
The coordination of nuclear and mitochondrial communication during aging and calorie restriction.
TL;DR: This review will focus on PGC-1alpha, SIRT1, AMPK and mTOR and discuss how these proteins regulate mitochondrial function and their potential involvement in aging, calorie restriction and age-related disease.
Identification of Selective Inhibitors of Cancer Stem Cells by High-Throughput Screening
Piyush Gupta,Piyush Gupta,Tamer T. Onder,Guozhi Jiang,Guozhi Jiang,Kai Tao,Charlotte Kuperwasser,Robert A. Weinberg,Eric S. Lander +8 more
TL;DR: In this article, an approach to screening for agents with epithelial CSC-specific toxicity was proposed and implemented in a chemical screen and discovered compounds showing selective toxicity for breast CSCs.
Journal ArticleDOI
Identification of a Genetic Signature of Activated Signal Transducer and Activator of Transcription 3 in Human Tumors
James V. Alvarez,Phillip G. Febbo,Phillip G. Febbo,Sridhar Ramaswamy,Massimo Loda,Andrea L. Richardson,David A. Frank +6 more
TL;DR: A system to express a constitutively active form of STAT3, STAT3-C, in mouse fibroblasts is created and it is shown that a subset of these targets, which include transcription factors regulating cell growth, survival, and differentiation, are coexpressed in a range of human tumors.
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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