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In Search of Newer Targets for Inflammatory Bowel Disease: A Systems and a Network Medicine Approach

Takashi Kitani et al

Takashi Kitani, Sushma C. Maddipatla, Ramya Madupuri, Christopher Greco, Jonathan Hartmann, James N. Baraniuk, and Sona Vasudevan

https://www.liebertpub.com/doi/10.1089/nsm.2020.0012

Abstract

Introduction: Crohn's disease and ulcerative colitis, both under the umbrella of inflammatory bowel diseases (IBD), involve many distinct molecular processes. The difference in their molecular processes is studied by using the different genes involved in each disease, and it is explored further for drug targeting and drug repurposing.

Methods: The initial set of genes was obtained by mining published literature and several curated databases. The identified genes were then subject to Systems and Network analysis to reveal their molecular processes and shed some light on their pathogenesis. Such methodologies have identified newer targets and drugs that can be repurposed.

Results: We use a Systems and Network Medicine approach to understand the mechanism of actions of genes involved in IBD. From an initial set of genes mined from literature and curated databases, we used the Multi-Steiner Tree algorithm implemented within the CoVex systems medicine platform to expand each disease module by incorporating candidate genes with significant connections to the disease-related seed genes. Such expanded disease modules will identify a larger set of potential targets and drugs. We used the Closeness Centrality algorithm implemented within CoVex to search for newer targets and repurposable drugs. Through a network medicine approach, we provide a mechanistic view of the diseases and point to newer drugs and targets.

Conclusion: We demonstrate that the Systems and Network Medicine approach is a powerful way to understand diseases and understand their mechanisms of action.

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