The regulon enrichment on gene expression signatures was tested by the VIPER algorithm. First, the gene expression signature was obtained by comparing two groups of samples representing distinctive phenotypes or treatments. In the next step, regulon enrichment on the gene expression signature can be computed using analytic rank-based enrichment analysis (56). At the end, significance values (P value and normalized enrichment score) were computed by comparing each regulon enrichment score to a null model generated by randomly and uniformly permuting the samples 1000 times. The output of VIPER is a list of highly active MRs as well as their activity scores and their enrichment P values. Further information about VIPER can be accessed in (18).

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