On testing the significance of sets of genes

B Efron, R Tibshirani - 2007 - projecteuclid.org
2007projecteuclid.org
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 …
Abstract
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 class predictions. We also describe a new R language package GSA that implements our ideas.
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