Reply to "Statistical concerns about the GSEA procedure"

In reply

Our manuscript¹ described Gene Set Enrichment Analysis (GSEA) as “designed to detect subtle but coordinated differences in expression of a priori defined sets of functionally related genes.” The method requires two inputs: (i) a list of genes that have been ranked according to expression difference between two states and (ii) a priori defined gene sets (e.g., pathways), each consisting of members drawn from this list. A gene set then receives an enrichment score (ES) that is a measure of statistical evidence rejecting the null hypothesis that its members are randomly distributed in the ordered list. By definition, the ES is a function of the size of a gene set, the total number of genes in the entire list and the relative ranks of the members of the gene set.