Abstract

Combining path consistency (PC) algorithms with conditional mutual information (CMI) are widely used in reconstruction of gene regulatory networks. CMI has many advantages over Pearson correlation coefficient in measuring non-linear dependence to infer gene regulatory networks. It can also discriminate the direct regulations from indirect ones. However, it is still a challenge to select the conditional genes in an optimal way, which affects the performance and computation complexity of the PC algorithm. In this study, we develop a novel conditional mutual information-based algorithm, namely RPNI (Regulation Pattern based Network Inference), to infer gene regulatory networks. For conditional gene selection, we define the co-regulation pattern, indirect-regulation pattern and mixture-regulation pattern as three candidate patterns to guide the selection of candidate genes. To demonstrate the potential of our algorithm, we apply it to gene expression data from DREAM challenge. Experimental results show that RPNI outperforms existing conditional mutual information-based methods in both accuracy and time complexity for different sizes of gene samples. Furthermore, the robustness of our algorithm is demonstrated by noisy interference analysis using different types of noise.

Highlights

  • Inferring gene regulatory networks is a key step in understanding biological processes [1,2,3,4,5]

  • In order to compare our method with conditional mutual information (CMI) and CMI2, we apply these methods to infer gene regulatory networks using the same dataset from DREAM3 challenge and acute myeloid leukemia (AML) based on the Level-3 processed RNA sequencing data of AML patient from TCGA [29, 30]

  • We propose three candidate patterns, namely co-regulation pattern, indirect-regulation pattern and mix-regulation pattern, to guide the choice of candidate genes

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Summary

Introduction

Inferring gene regulatory networks is a key step in understanding biological processes [1,2,3,4,5]. Many computational methods were developed to infer gene regulatory networks using these high-throughput data [2, 4]. These methods can be divided into two categories: the model-based and the machine learning-based approaches [3]. Bayesian networks, Pearson correlation coefficient, partial correlation coefficients, information theory, and conditional mutual information are applied to measure the regulation strength between genes. Bayesian networks are based on maximizing the scoring function, for the moment, dynamic programming is PLOS ONE | DOI:10.1371/journal.pone.0154953. Bayesian networks are based on maximizing the scoring function, for the moment, dynamic programming is PLOS ONE | DOI:10.1371/journal.pone.0154953 May 12, 2016

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