Abstract

BackgroundHigh throughput techniques produce multiple functional association networks. Integrating these networks can enhance the accuracy of protein function prediction. Many algorithms have been introduced to generate a composite network, which is obtained as a weighted sum of individual networks. The weight assigned to an individual network reflects its benefit towards the protein functional annotation inference. A classifier is then trained on the composite network for predicting protein functions. However, since these techniques model the optimization of the composite network and the prediction tasks as separate objectives, the resulting composite network is not necessarily optimal for the follow-up protein function prediction.ResultsWe address this issue by modeling the optimization of the composite network and the prediction problems within a unified objective function. In particular, we use a kernel target alignment technique and the loss function of a network based classifier to jointly adjust the weights assigned to the individual networks. We show that the proposed method, called MNet, can achieve a performance that is superior (with respect to different evaluation criteria) to related techniques using the multiple networks of four example species (yeast, human, mouse, and fly) annotated with thousands (or hundreds) of GO terms.ConclusionMNet can effectively integrate multiple networks for protein function prediction and is robust to the input parameters. Supplementary data is available at https://sites.google.com/site/guoxian85/home/mnet. The Matlab code of MNet is available upon request.

Highlights

  • Determining the functional roles of proteins is important to understand life at molecular level and has great biomedical and pharmaceutical implications [1,2,3]

  • We show that the unified objective function can boost the accuracy of protein function prediction according to several evaluation criteria

  • We annotated the proteins in each dataset using the recently updated Gene Ontology (GO) term annotation in three sub-ontologies, namely biological process (BP) functions, molecular functions (MF), and cellular component (CC) functions, respectively

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Summary

Introduction

Determining the functional roles of proteins is important to understand life at molecular level and has great biomedical and pharmaceutical implications [1,2,3]. A number of computational methods have been suggested to integrate heterogeneous data for inferring protein (or gene) functions [6,13]. Most of these techniques follow the same basic paradigm: first, they generate various functional association networks (one or more networks for one data source) that encode the implicit information of shared functions of proteins in each data source. High throughput techniques produce multiple functional association networks Integrating these networks can enhance the accuracy of protein function prediction. Since these techniques model the optimization of the composite network and the prediction tasks as separate objectives, the resulting composite network is not necessarily optimal for the follow-up protein function prediction

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