On testing the signicance of sets of genes

This paper discusses the problem of identifying dierentially ex-pressed groups of genes from a microarray experiment. The groups of genes are externally dened, for example, sets of gene pathways derived from biological databases. Our starting point is the interest-ing Gene Set Enrichment Analysis (GSEA) procedure of Subramanian et al. (2005). We study the problem in some generality and propose two potential improvements to GSEA: the maxmean statistic for sum-marizing 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 lan-guage package GSA that implements our ideas.