The Gene Ontology (GO) Consortium <https://geneontology.org/> organizes genes into hierarchical categories based on biological process (BP), molecular function (MF) and cellular component (CC, i.e., subcellular localization). Tools such as GoMiner (see Zeeberg, B.R., Feng, W., Wang, G. et al. (2003) <doi:10.1186/gb-2003-4-4-r28>) can leverage GO to perform ontological analysis of microarray and proteomics studies, typically generating a list of significant functional categories. The significance is traditionally determined by randomizing the input gene list to computing the false discovery rate (FDR) of the enrichment p-value for each category. We explore here the novel alternative of randomizing the GO database rather than the gene list.