Improving GO semantic similarity measures by exploring the ontology beneath the terms and modelling uncertainty

Results: To show that our approach can potentially improve any semantic similarity measure, we test it on six different semantic similarity measures: three commonly used measures by Resnik (1999), Lin (1998), and Jiang and Conrath (1997); and three recently proposed measures: simUI, simGIC by Pesquita et al. (2008); GraSM by Couto et al. (2007); and Couto and Silva (2011). We applied these improved measures to the GO annotations of the yeast Saccharomyces cerevisiae, and tested how they correlate with sequence similarity, mRNA co-expression and protein-protein interaction data. Our results consistently show that the use of downward random walks leads to more reliable similarity measures.