In silico prediction of physical protein interactions and characterization of interactome orphans

计算机预测蛋白质的物理相互作用和相互作用组孤儿的表征

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作者:Max Kotlyar, Chiara Pastrello, Flavia Pivetta, Alessandra Lo Sardo, Christian Cumbaa, Han Li, Taline Naranian, Yun Niu, Zhiyong Ding, Fatemeh Vafaee, Fiona Broackes-Carter, Julia Petschnigg, Gordon B Mills, Andrea Jurisicova, Igor Stagljar, Roberta Maestro, Igor Jurisica

Abstract

Protein-protein interactions (PPIs) are useful for understanding signaling cascades, predicting protein function, associating proteins with disease and fathoming drug mechanism of action. Currently, only ∼ 10% of human PPIs may be known, and about one-third of human proteins have no known interactions. We introduce FpClass, a data mining-based method for proteome-wide PPI prediction. At an estimated false discovery rate of 60%, we predicted 250,498 PPIs among 10,531 human proteins; 10,647 PPIs involved 1,089 proteins without known interactions. We experimentally tested 233 high- and medium-confidence predictions and validated 137 interactions, including seven novel putative interactors of the tumor suppressor p53. Compared to previous PPI prediction methods, FpClass achieved better agreement with experimentally detected PPIs. We provide an online database of annotated PPI predictions (http://ophid.utoronto.ca/fpclass/) and the prediction software (http://www.cs.utoronto.ca/~juris/data/fpclass/).

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