PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes
PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes
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DOI：
10.1038/ng1180
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发表时间：
2003-07-01
期刊：
影响因子：
30.8
通讯作者：
Groop, LC
中科院分区：
文献类型：
--
作者：
Mootha, VK;Lindgren, CM;Groop, LC
DNA微阵列可用于鉴定人类疾病的基因表达变化特征。然而，当相关差异在个体基因水平上很微妙时，这是具有挑战性的。我们介绍了一种分析策略，基因集富集分析，旨在检测适度，但协调的功能相关基因组的表达变化。使用这种方法，我们确定了一组参与氧化磷酸化的基因，其表达在人类糖尿病肌肉中协调降低。这些基因的表达在胰岛素介导的葡萄糖处理位点高，由PGC-1 α激活，并与全身有氧能力相关。我们的研究结果与临床上重要的人类代谢的变化，并说明在基因组分析实验的路径关系的价值。
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-1alpha 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.