Filtering high-throughput protein-protein interaction data using a combination of genomic features

In this study, we use a combination of 3 genomic features – structurally known interacting Pfam domains, Gene Ontology annotations and sequence homology – as a means to assign reliability to the protein-protein interactions in Saccharomyces cerevisiae determined by high-throughput experiments. Using Bayesian network approaches, we show that protein-protein interactions from high-throughput data supported by one or more genomic features have a higher likelihood ratio and hence are more likely to be real interactions. Our method has a high sensitivity (90%) and good specificity (63%). We show that 56% of the interactions from high-throughput experiments in Saccharomyces cerevisiae have high reliability. We use the method to estimate the number of true interactions in the high-throughput protein-protein interaction data sets in Caenorhabditis elegans, Drosophila melanogaster and Homo sapiens to be 27%, 18% and 68% respectively. Our results are available for searching and downloading at http://helix.protein.osaka-u.ac.jp/htp/ webcite.A combination of genomic features that include sequence, structure and annotation information is a good predictor of true interactions in large and noisy high-throughput data sets. The method has a very high sensitivity and good specificity and can be used to assign a likelihood ratio, corresponding to the reliability, to each interaction.Protein-protein interactions in various organisms are increasingly becoming the focus of study in the identification of cellular functions of proteins. Though small scale experiments have contributed significantly to our knowledge of protein-protein interactions, the bulk of the data is available from high-throughput methods like yeast two hybrid (Y2H) and mass spectrometry of coimmunoprecipitated complexes (Co-IP) [1]. Such data is currently available for H. pylori [2], S. cerevisiae (baker's yeast) [3-6], C. elegans [7], D. melanogaster [8] and H. sapiens [9]. However, protein-protein interaction data ob