Predictive integration of gene ontology-driven similarity and functional interactions

There is a need to develop methods to automatically incorporate prior knowledge to support the prediction and validation of novel functional associations. One such important source is represented by the Gene Ontology (GO)(TM) and the many model organism databases of gene products annotated to the GO. We investigated quantitative relationships between the GO-driven similarity of genes and their functional interactions by analyzing different types of associations in Saccharomyces cerevisiae and Caenorhabditis elegans. Interacting genes exhibited significantly higher levels of GO-driven similarity (GOS) in comparison to random pairs of genes used as a surrogate for negative interactions. The Biological Process hierarchy provides more reliable results for co-regulatory and protein-protein interactions. GOS represent a relevant resource to support prediction of functional networks in combination with other resources.