Inferring Gene Regulatory Networks Using Conditional Regulation Pattern to Guide Candidate Genes

PLoS One. 2016 May 12;11(5):e0154953. doi: 10.1371/journal.pone.0154953. eCollection 2016.

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.

MeSH terms

  • Algorithms
  • Computer Simulation
  • Databases, Genetic
  • Gene Expression Regulation*
  • Gene Regulatory Networks*
  • Genetic Association Studies*
  • Humans
  • Leukemia, Myeloid, Acute / genetics
  • Principal Component Analysis
  • ROC Curve
  • Saccharomyces cerevisiae / genetics

Grants and funding

This work was supported by the NSFC (Grant No.61532014 & No.61432010 & No.61402349), and the Fundamental Research Funds for the Central Universities (No. BDZ021404) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.