A New Family of Similarity Measures for Scoring Confidence of Protein Interactions Using Gene Ontology.

Abstract

The large-scale protein-protein interaction (PPI) data has the potential to play a significant role in the endeavor of understanding cellular processes. However, the presence of a considerable fraction of false positives is a bottleneck in realizing this potential. There have been continuous efforts to utilize complementary resources for scoring confidence of PPIs in a manner that false positive interactions get a low confidence score. Gene Ontology (GO), a taxonomy of biological terms to represent the properties of gene products and their relations, has been widely used for this purpose. We utilize GO to introduce a new set of specificity measures: Relative Depth Specificity (RDS), Relative Node-based Specificity (RNS), and Relative Edge-based Specificity (RES), leading to a new family of similarity measures. We use these similarity measures to obtain a confidence score for each PPI. We evaluate the new measures using four different benchmarks. We show that all the three measures are quite effective. Notably, RNS and RES more effectively distinguish true PPIs from false positives than the existing alternatives. RES also shows a robust set-discriminating power and can be useful for protein functional clustering as well.