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

Enrico Maiorino (), Seung Han Baek, Feng Guo, Xiaobo Zhou, Parul H. Kothari, Edwin K. Silverman, Albert-László Barabási, Scott T. Weiss, Benjamin A. Raby and Amitabh Sharma
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Enrico Maiorino: Harvard Medical School
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
Scott T. Weiss: Harvard Medical School
Benjamin A. Raby: Harvard Medical School
Amitabh Sharma: Harvard Medical School

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-14600-w

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