Abstract

BackgroundAccurate annotation of protein functions is still a big challenge for understanding life in the post-genomic era. Many computational methods based on protein-protein interaction (PPI) networks have been proposed to predict the function of proteins. However, the precision of these predictions still needs to be improved, due to the incompletion and noise in PPI networks. Integrating network topology and biological information could improve the accuracy of protein function prediction and may also lead to the discovery of multiple interaction types between proteins. Current algorithms generate a single network, which is archived using a weighted sum of all types of protein interactions.MethodThe influences of different types of interactions on the prediction of protein functions are not the same. To address this, we construct multilayer protein networks (MPN) by integrating PPI networks, the domain of proteins, and information on protein complexes. In the MPN, there is more than one type of connections between pairwise proteins. Different types of connections reflect different roles and importance in protein function prediction. Based on the MPN, we propose a new protein function prediction method, named function prediction based on multilayer protein networks (FP-MPN). Given an un-annotated protein, the FP-MPN method visits each layer of the MPN in turn and generates a set of candidate neighbors with known functions. A set of predicted functions for the testing protein is then formed and all of these functions are scored and sorted. Each layer plays different importance on the prediction of protein functions. A number of top-ranking functions are selected to annotate the unknown protein.ConclusionsThe method proposed in this paper was a better predictor when used on Saccharomyces cerevisiae protein data than other function prediction methods previously used. The proposed FP-MPN method takes different roles of connections in protein function prediction into account to reduce the artificial noise by introducing biological information.Electronic supplementary materialThe online version of this article (doi:10.1186/s40246-016-0087-x) contains supplementary material, which is available to authorized users.

Highlights

  • Accurate annotation of protein functions is still a big challenge for understanding life in the postgenomic era

  • The method proposed in this paper was a better predictor when used on Saccharomyces cerevisiae protein data than other function prediction methods previously used

  • The proposed FP-multilayer protein networks (MPN) method takes different roles of connections in protein function prediction into account to reduce the artificial noise by introducing biological information

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Summary

Introduction

Accurate annotation of protein functions is still a big challenge for understanding life in the postgenomic era. Many computational methods based on protein-protein interaction (PPI) networks have been proposed to predict the function of proteins. Integrating network topology and biological information could improve the accuracy of protein function prediction and may lead to the discovery of multiple interaction types between proteins. The past decade has witnessed a rapid development of computational methods for predicting protein functions from PPI datasets. A neighbor counting (NC) method proposed by Schwikowski et al [6] predicted an unannotated protein with the functions that occurred most frequently among its neighbor proteins. This method ignored the background frequency of different function annotations. Hishigaki et al [7] improved the

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