Identification of genes related to proliferative diabetic retinopathy through RWR algorithm based on protein-protein interaction network.

Journal: Biochimica et biophysica acta. Molecular basis of disease
Published Date:

Abstract

Proliferative diabetic retinopathy (PDR) is one of the most common complications of diabetes and can lead to blindness. Proteomic studies have provided insight into the pathogenesis of PDR and a series of PDR-related genes has been identified but are far from fully characterized because the experimental methods are expensive and time consuming. In our previous study, we successfully identified 35 candidate PDR-related genes through the shortest-path algorithm. In the current study, we developed a computational method using the random walk with restart (RWR) algorithm and the protein-protein interaction (PPI) network to identify potential PDR-related genes. After some possible genes were obtained by the RWR algorithm, a three-stage filtration strategy, which includes the permutation test, interaction test and enrichment test, was applied to exclude potential false positives caused by the structure of PPI network, the poor interaction strength, and the limited similarity on gene ontology (GO) terms and biological pathways. As a result, 36 candidate genes were discovered by the method which was different from the 35 genes reported in our previous study. A literature review showed that 21 of these 36 genes are supported by previous experiments. These findings suggest the robustness and complementary effects of both our efforts using different computational methods, thus providing an alternative method to study PDR pathogenesis.

Authors

  • Jian Zhang
    College of Pharmacy, Ningxia Medical University, Yinchuan, NingxiaHui Autonomous Region, China.
  • Yan Suo
    Department of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, China; Shanghai Key Laboratory of Fundus Disease, Shanghai, China; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China.
  • Min Liu
    Department of Critical Care Medicine, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, China.
  • Xun Xu
    BGI-Shenzhen, Shenzhen 518083, China.