Assessing reliability of protein-protein interactions by gene ontology integration

Recent advances in genome-wide identification of protein-protein interactions (PPIs) have produced an abundance of interaction data which give an insight into functional associations among proteins. However, it is known that the PPI datasets determined by high-throughput experiments or inferred by computational methods include an extremely large number of false positives. Using Gene Ontology (GO) and its annotations, we assess reliability of the PPIs by considering the semantic similarity of interacting proteins. Protein pairs with high semantic similarity are considered highly likely to share common functions, and therefore, are more likely to interact. We analyze the performance of existing semantic similarity measures in terms of functional consistency and propose a combined method that achieves improved performance over existing methods. The semantic similarity measures are applied to identify false positive PPIs. The classification results show that the combined hybrid method has higher accuracy than the other existing measures. Furthermore, the combined hybrid classifier predicts that 59.6% of the S. cerevisiae PPIs from the BioGRID database are false positives.