Building the drug-GO function network to screen significant candidate drugs for myasthenia gravis.

Journal: PloS one
PMID: 30947317

Abstract

Myasthenia gravis (MG) is an autoimmune disease. In recent years, considerable evidence has indicated that Gene Ontology (GO) functions, especially GO-biological processes, have important effects on the mechanisms and treatments of different diseases. However, the roles of GO functions in the pathogenesis and treatment of MG have not been well studied. This study aimed to uncover the potential important roles of risk-related GO functions and to screen significant candidate drugs related to GO functions for MG. Based on MG risk genes, 238 risk GO functions and 42 drugs were identified. Through constructing a GO function network, we discovered that positive regulation of NF-kappaB transcription factor activity (GO:0051092) may be one of the most important GO functions in the mechanism of MG. Furthermore, we built a drug-GO function network to help evaluate the latent relationship between drugs and GO functions. According to the drug-GO function network, 5 candidate drugs showing promise for treating MG were identified. Indeed, 2 out of 5 candidate drugs have been investigated to treat MG. Through functional enrichment analysis, we found that the mechanisms between 5 candidate drugs and associated GO functions may involve two vital pathways, specifically hsa05332 (graft-versus-host disease) and hsa04940 (type I diabetes mellitus). More interestingly, most of the processes in these two pathways were consistent. Our study will not only reveal a new perspective on the mechanisms and novel treatment strategies of MG, but also will provide strong support for research on GO functions.

Authors

  • Shuang Li
    Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China.
  • Yuze Cao
    Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China.
  • Lei Li
    Department of Thoracic Surgery, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, China.
  • Huixue Zhang
    Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China.
  • Xiaoyu Lu
    Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China.
  • Chunrui Bo
    Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China.
  • Xiaotong Kong
    Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China.
  • Zhaojun Liu
    Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China.
  • Lixia Chen
    Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China.
  • Peifang Liu
    Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China.
  • Yang Jiao
    Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China.
  • Jianjian Wang
    Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China.
  • Shangwei Ning
    College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang Province, China.
  • Lihua Wang
    Division of Physical Biology & Bioimaging Center, Shanghai Synchrotron Radiation Facility, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China.

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