Network propagation with dual flow for gene prioritization

PLoS One. 2015 Feb 17;10(2):e0116505. doi: 10.1371/journal.pone.0116505. eCollection 2015.

Abstract

Based on the hypothesis that the neighbors of disease genes trend to cause similar diseases, network-based methods for disease prediction have received increasing attention. Taking full advantage of network structure, the performance of global distance measurements is generally superior to local distance measurements. However, some problems exist in the global distance measurements. For example, global distance measurements may mistake non-disease hub proteins that have dense interactions with known disease proteins for potential disease proteins. To find a new method to avoid the aforementioned problem, we analyzed the differences between disease proteins and other proteins by using essential proteins (proteins encoded by essential genes) as references. We find that disease proteins are not well connected with essential proteins in the protein interaction networks. Based on this new finding, we proposed a novel strategy for gene prioritization based on protein interaction networks. We allocated positive flow to disease genes and negative flow to essential genes, and adopted network propagation for gene prioritization. Experimental results on 110 diseases verified the effectiveness and potential of the proposed method.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Computational Biology / methods
  • Databases, Genetic
  • Gene Regulatory Networks*
  • Genetic Association Studies
  • Genetic Diseases, Inborn / genetics*
  • Genetic Diseases, Inborn / metabolism
  • Humans
  • Leukoencephalopathies / genetics
  • Leukoencephalopathies / metabolism
  • Models, Statistical
  • Protein Interaction Maps
  • ROC Curve
  • Reproducibility of Results

Grants and funding

1. The State Key Program of National Natural Science of China (No. 91130035), National Natural Science Foundation of China (http://www.nsfc.gov.cn/), FS; 2. The National Science Foundation of Shandong Province (No. ZR2012FZ003), Shandong Provincial Natural Science Foundation, China (http://www.sdnsf.gov.cn/portal/), FS; 3. The National Science Foundation of Shandong Province (No. ZR2012FQ017), Shandong Provincial Natural Science Foundation, China (http://www.sdnsf.gov.cn/portal/), RS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.