A schematic overview of the GAGE algorithm. GAGE has three major steps. (a) Step 1: input preparation. Separate gene sets into two categories: experimental sets and canonical pathways, for differential treatment in significant test. (b) Step 2: gene set differential expression tests based on one-on-one comparison between samples from the two experimental conditions. For each experiment-control pair, calculate differential expression in log based fold change for all genes. Test whether specific gene sets are significantly differentially expressed relative to the background whole set using two-sample t-test. (c) Step 3: summarization. For each gene set, derive a global p-value based on a meta-test on the negative log sum of p-values from all one-on-one comparisons. More details of GAGE are given in the Methods. Variables m, s and n are the mean fold change, standard deviation and number of genes in a gene set, M, S and N are those for the whole set. A similar schematic overview of the PAGE algorithm is shown in Additional file 1: Supplementary Figure 1.