Abstract

BackgroundProtein-protein interactions (PPIs) play crucial roles in virtually every aspect of cellular function within an organism. Over the last decade, the development of novel high-throughput techniques has resulted in enormous amounts of data and provided valuable resources for studying protein interactions. However, these high-throughput protein interaction data are often associated with high false positive and false negative rates. It is therefore highly desirable to develop scalable methods to identify these errors from the computational perspective.ResultsWe have developed a robust computational technique for assessing the reliability of interactions and predicting new interactions by combining manifold embedding with multiple information integration. Validation of the proposed method was performed with extensive experiments on densely-connected and sparse PPI networks of yeast respectively. Results demonstrate that the interactions ranked top by our method have high functional homogeneity and localization coherence.ConclusionsOur proposed method achieves better performances than the existing methods no matter assessing or predicting protein interactions. Furthermore, our method is general enough to work over a variety of PPI networks irrespectively of densely-connected or sparse PPI network. Therefore, the proposed algorithm is a much more promising method to detect both false positive and false negative interactions in PPI networks.

Highlights

  • Protein-protein interactions (PPIs) play crucial roles in virtually every aspect of cellular function within an organism

  • Results we firstly quantify the success of embedding PPI network into low dimensional metric space using probability density function and Receiver Operator Characteristic (ROC) curve which are learned from the data given by manifold embedding

  • The performance of the proposed approach is evaluated using functional homogeneity and localization coherence of protein interactions from four PPI networks that are derived from various scales and high-throughput techniques, i.e., yeasttwo-hybrid (Y2H), tandem affinity purification (TAP), and mass spectrometry (MS)

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Summary

Introduction

Protein-protein interactions (PPIs) play crucial roles in virtually every aspect of cellular function within an organism. The development of novel high-throughput techniques has resulted in enormous amounts of data and provided valuable resources for studying protein interactions. These high-throughput protein interaction data are often associated with high false positive and false negative rates. The development of novel high-throughput techniques, such as yeast-twohybrid (Y2H), tandem affinity purification (TAP), and mass spectrometry (MS), has resulted in a rapid accumulation of data that provide a global description of the whole network of PPI for many organisms [1]. Chua et al [8] introduced an index called FSWeight that exploits indirect neighbors to predict protein functions

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