Abstract

BackgroundProtein-protein interactions (PPIs) play important roles in various cellular processes. However, the low quality of current PPI data detected from high-throughput screening techniques has diminished the potential usefulness of the data. We need to develop a method to address the high data noise and incompleteness of PPI data, namely, to filter out inaccurate protein interactions (false positives) and predict putative protein interactions (false negatives).ResultsIn this paper, we proposed a novel two-step method to integrate diverse biological and computational sources of supporting evidence for reliable PPIs. The first step, interaction binning or InterBIN, groups PPIs together to more accurately estimate the likelihood (Bin-Confidence score) that the protein pairs interact for each biological or computational evidence source. The second step, interaction classification or InterCLASS, integrates the collected Bin-Confidence scores to build classifiers and identify reliable interactions.ConclusionsWe performed comprehensive experiments on two benchmark yeast PPI datasets. The experimental results showed that our proposed method can effectively eliminate false positives in detected PPIs and identify false negatives by predicting novel yet reliable PPIs. Our proposed method also performed significantly better than merely using each of individual evidence sources, illustrating the importance of integrating various biological and computational sources of data and evidence.

Highlights

  • Protein-protein interactions (PPIs) play important roles in various cellular processes

  • We describe our InterCLASS method that exploits the integration of the evidences re-weighted using Bin-Confidence scores and infers reliable PPIs using machine learning methods such as Support Vector Machines (SVM) and Bayesian classifier (BC)

  • We show that our integrating method is very effective in identifying false negatives and false positives than existing methods

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Summary

Introduction

Protein-protein interactions (PPIs) play important roles in various cellular processes. The low quality of current PPI data detected from high-throughput screening techniques has diminished the potential usefulness of the data. The highthroughput methods can be biased against soluble or membrane proteins and fail to detect certain types of interactions such as weak transient interactions and interactions that require post-translational modification. This results in false negative detection and low experimental coverage of the interactomes [6,7]

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