Predicting protein–protein interactions using signature products

Abstract

Motivation: Proteome-wide prediction of protein–protein interaction is a difficult and important problem in biology. Although there have been recent advances in both experimental and computational methods for predicting protein–protein interactions, we are only beginning to see a confluence of these techniques. In this paper, we describe a very general, high-throughput method for predicting protein–protein interactions. Our method combines a sequence-based description of proteins with experimental information that can be gathered from any type of protein–protein interaction screen. The method uses a novel description of interacting proteins by extending the signature descriptor, which has demonstrated success in predicting peptide/protein binding interactions for individual proteins. This descriptor is extended to protein pairs by taking signature products. The signature product is implemented within a support vector machine classifier as a kernel function. Results: We have applied our method to publicly available yeast, Helicobacter pylori, human and mouse datasets. We used the yeast and H.pylori datasets to verify the predictive ability of our method, achieving from 70 to 80% accuracy rates using 10-fold cross-validation. We used the human and mouse datasets to demonstrate that our method is capable of cross-species prediction. Finally, we reused the yeast dataset to explore the ability of our algorithm to predict domains. Contact: smartin@sandia.gov.