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Discovering disease-associated genes in weighted protein–protein interaction networks

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  • Cui, Ying
  • Cai, Meng
  • Stanley, H. Eugene

Abstract

Although there have been many network-based attempts to discover disease-associated genes, most of them have not taken edge weight – which quantifies their relative strength – into consideration. We use connection weights in a protein–protein interaction (PPI) network to locate disease-related genes. We analyze the topological properties of both weighted and unweighted PPI networks and design an improved random forest classifier to distinguish disease genes from non-disease genes. We use a cross-validation test to confirm that weighted networks are better able to discover disease-associated genes than unweighted networks, which indicates that including link weight in the analysis of network properties provides a better model of complex genotype–phenotype associations.

Suggested Citation

  • Cui, Ying & Cai, Meng & Stanley, H. Eugene, 2018. "Discovering disease-associated genes in weighted protein–protein interaction networks," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 496(C), pages 53-61.
    • Handle: RePEc:eee:phsmap:v:496:y:2018:i:c:p:53-61
    DOI: 10.1016/j.physa.2017.12.080
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    References listed on IDEAS

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    1. Wu, Shun-yao & Shao, Feng-jing & Sun, Ren-cheng & Sui, Yi & Wang, Ying & Wang, Jin-long, 2014. "Analysis of human genes with protein–protein interaction network for detecting disease genes," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 398(C), pages 217-228.
    2. U Martin Singh-Blom & Nagarajan Natarajan & Ambuj Tewari & John O Woods & Inderjit S Dhillon & Edward M Marcotte, 2013. "Prediction and Validation of Gene-Disease Associations Using Methods Inspired by Social Network Analyses," PLOS ONE, Public Library of Science, vol. 8(5), pages 1-17, May.
    3. Jianhua Li & Xiaoyan Lin & Yueyang Teng & Shouliang Qi & Dayu Xiao & Jianying Zhang & Yan Kang, 2016. "A Comprehensive Evaluation of Disease Phenotype Networks for Gene Prioritization," PLOS ONE, Public Library of Science, vol. 11(7), pages 1-18, July.
    4. Oron Vanunu & Oded Magger & Eytan Ruppin & Tomer Shlomi & Roded Sharan, 2010. "Associating Genes and Protein Complexes with Disease via Network Propagation," PLOS Computational Biology, Public Library of Science, vol. 6(1), pages 1-9, January.
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