Gene ontology fuzzy-enrichment analysis to investigate drug mode-of-action

We investigated the possibility of gaining information on the mode of action of a set of compounds by means of Gene Ontology (GO) enrichment analysis. To this aim, we developed a new method, based on fuzzy-sets, which is able to compute sets of genes that are consistently differentially expressed when treating cells with the analyzed compounds. Then a Gene Ontology enrichment analysis is performed on these sets. The method has been tested on several different groups of drugs, whose similarity in mode of action has been predicted by a gene-expression based, unsupervised, approach and verified by searching literature. The obtained results show that GO terms that are overrepresented in these fuzzy sets provide a quick and "easy-tointerpret" view of the mode of action of the analyzed drugs.