Prediction of protein-protein interactions using protein signature profiling.
Protein domains are conserved and functionally independent structures that play an important role in interactions among related proteins. Domain-domain interactions have been recently used to predict protein-protein interactions (PPI). In general, the interaction probability of a pair of domains is scored using a trained scoring function. Satisfying a threshold, the protein pairs carrying those domains are regarded as "interacting". In this study, the signature contents of proteins were utilized to predict PPI pairs in Saccharomyces cerevisiae, Caenorhabditis elegans, and Homo sapiens. Similarity between protein signature patterns was scored and PPI predictions were drawn based on the binary similarity scoring function. Results show that the true positive rate of prediction by the proposed approach is approximately 32% higher than that using the maximum likelihood estimation method when compared with a test set, resulting in 22% increase in the area under the receiver operating characteristic (ROC) curve. When proteins containing one or two signatures were removed, the sensitivity of the predicted PPI pairs increased significantly. The predicted PPI pairs are on average 11 times more likely to interact than the random selection at a confidence level of 0.95, and on average 4 times better than those predicted by either phylogenetic profiling or gene expression profiling.
Mahdavi
Mahmood A
MA
Department of Chemical Engineering, University of Saskatchewan, Saskatoon, SK S7N 5A9, Canada.
Lin
Yen-Han
YH
D000818:Animals; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016001:Confidence Intervals; D030562:Databases, Protein; D020869:Gene Expression Profiling / Q000706:statistics & numerical data; D006801:Humans; D016013:Likelihood Functions; D010802:Phylogeny; D040081:Protein Array Analysis / Q000379:methods* / Q000706:statistics & numerical data; D025941:Protein Interaction Mapping / Q000379:methods* / Q000706:statistics & numerical data; D017434:Protein Structure, Tertiary; D012372:ROC Curve; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012680:Sensitivity and Specificity
D029742:Caenorhabditis elegans Proteins; D029701:Saccharomyces cerevisiae Proteins