Gene set enrichment analysis made simple

Among the many applications of microarray technology, one of the most popular is the identification of genes that are differentially expressed in two conditions. A common statistical approach is to quantify the interest of each gene with a p-value, adjust these p-values for multiple comparisons, choose an appropriate cut-off, and create a list of candidate genes. This approach has been criticised for ignoring biological knowledge regarding how genes work together. Recently a series of methods, that do incorporate biological knowledge, have been proposed. However, the most popular method, gene set enrichment analysis (GSEA), seems overly complicated. Furthermore, GSEA is based on a statistical test known for its lack of sensitivity. In this article we compare the performance of a simple alternative to GSEA. We find that this simple solution clearly outperforms GSEA. We demonstrate this with eight different microarray datasets.