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Discovering the genes mediating the interactions between chronic respiratory diseases in the human interactome

Author

Listed:
  • Enrico Maiorino

    (Harvard Medical School
    Northeastern University)

  • Seung Han Baek

    (Harvard Medical School)

  • Feng Guo

    (Harvard Medical School)

  • Xiaobo Zhou

    (Harvard Medical School)

  • Parul H. Kothari

    (Harvard Medical School)

  • Edwin K. Silverman

    (Harvard Medical School)

  • Albert-László Barabási

    (Harvard Medical School
    Northeastern University)

  • Scott T. Weiss

    (Harvard Medical School)

  • Benjamin A. Raby

    (Harvard Medical School)

  • Amitabh Sharma

    (Harvard Medical School)

Abstract

The molecular and clinical features of a complex disease can be influenced by other diseases affecting the same individual. Understanding disease-disease interactions is therefore crucial for revealing shared molecular mechanisms among diseases and designing effective treatments. Here we introduce Flow Centrality (FC), a network-based approach to identify the genes mediating the interaction between two diseases in a protein-protein interaction network. We focus on asthma and COPD, two chronic respiratory diseases that have been long hypothesized to share common genetic determinants and mechanisms. We show that FC highlights potential mediator genes between the two diseases, and observe similar outcomes when applying FC to 66 additional pairs of related diseases. Further, we perform in vitro perturbation experiments on a widely replicated asthma gene, GSDMB, showing that FC identifies candidate mediators of the interactions between GSDMB and COPD-associated genes. Our results indicate that FC predicts promising gene candidates for further study of disease-disease interactions.

Suggested Citation

  • Enrico Maiorino & Seung Han Baek & Feng Guo & Xiaobo Zhou & Parul H. Kothari & Edwin K. Silverman & Albert-László Barabási & Scott T. Weiss & Benjamin A. Raby & Amitabh Sharma, 2020. "Discovering the genes mediating the interactions between chronic respiratory diseases in the human interactome," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14600-w
    DOI: 10.1038/s41467-020-14600-w
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    Cited by:

    1. Zhang, Dongqing & Wallace, Stein W. & Guo, Zhaoxia & Dong, Yucheng & Kaut, Michal, 2021. "On scenario construction for stochastic shortest path problems in real road networks," Transportation Research Part E: Logistics and Transportation Review, Elsevier, vol. 152(C).

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