massiveGST: A Mann–Whitney–Wilcoxon Gene-Set Test Tool That Gives Meaning to Gene-Set Enrichment Analysis

Abstract

Gene-set enrichment analysis is the key methodology for obtaining biological information from transcriptomic space’s statistical result. Since its introduction, Gene-set Enrichment analysis methods have obtained more reliable results and a wider range of application. Great attention has been devoted to global tests, in contrast to competitive methods that have been largely ignored, although they appear more flexible because they are independent from the source of gene-profiles. We analyzed the properties of the Mann–Whitney–Wilcoxon test, a competitive method, and adapted its interpretation in the context of enrichment analysis by introducing a Normalized Enrichment Score that summarize two interpretations: a probability estimate and a location index. Two implementations are presented and compared with relevant literature methods: an R package and an online web tool. Both allow for obtaining tabular and graphical results with attention to reproducible research.

Keywords

• competitive enrichment methods
• gene-profile
• gene-sets ranking
• Kolmogorov–Smirnov’s test
• pathway analysis
• rank sum test