Permutation re-sampling  requires  a computationally demanding number of permutations to get reliable estimates of the p-values for the most differentially expressed genes, if n is large. Eisinga, Breitling and Heskes (2013) provide the exact probability mass distribution of the rank product statistic. Calculation of the exact p-values offers a substantial improvement over permutation approximation, most significantly for that part of the distribution rank product analysis is most interested in, i.e., the thin right tail. However, exact statistical significance of large rank products may take unacceptable long amounts of time to compute. Heskes, Eisinga and Breitling (2014) provide a method to determine accurate approximate p-values of the rank product statistic in a computationally fast manner.