ON TESTING THE SIGNIFICANCE OF SETS OF GENES

被引:554
作者
Efron, Bradley [1 ,2 ]
Tibshirani, Robert [1 ,2 ]
机构
[1] Stanford Univ, Dept Stat, Stanford, CA 94305 USA
[2] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA
基金
美国国家卫生研究院;
关键词
Multiple testing; gene set enrichment; hypothesis testing;
D O I
10.1214/07-AOAS101
中图分类号
O21 [概率论与数理统计]; C8 [统计学];
学科分类号
020208 ; 070103 ; 0714 ;
摘要
This paper discusses the problem of identifying differentially expressed groups of genes from a microarray experiment. The groups of genes are externally defined, for example, sets of gene pathways derived from biological databases. Our starting point is the interesting, Gene Set Enrichment Analysis (GSEA) procedure of Subramanian et al. [Proc. Natl. Acad. Sci. USA 102 (2005) 15545-15550]. We Study the problem in some generality and propose two potential improvements to GSEA: the maxmean statistic for summarizing, gene-sets, and restandardization for more accurate inferences. We discuss a variety of examples and extensions, including the use of gene-set scores for predictions. We also describe a new R language package GSA that implements our ideas.
引用
收藏
页码:107 / 129
页数:23
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