论文标题

寻找IBD的新目标:一种系统和网络医学方法

In Search of Newer Targets for IBD: A Systems and a Network Medicine Approach

论文作者

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

论文摘要

简介:克罗恩病和溃疡性结肠炎,均在炎症性肠病的伞下(IBD),涉及许多不同的分子过程。通过使用每种疾病中涉及的不同基因研究它们的分子过程差异,并进一步探讨了药物靶向和药物重新利用。方法:初始基因集是通过开采已发表的文献和几个策划数据库获得的。然后,鉴定的基因经过系统和网络分析,以揭示其分子过程,并阐明其发病机理。这种方法已经确定了可以重新使用的新靶和药物。结果:我们使用系统和网络医学方法来了解IBD中涉及的基因作用机理。从文献和策划数据库开采的一组基因中,我们使用了在Covex Systems Medicine Platform中实现的多型树木算法来扩展每个疾病模块,通过与与疾病相关的种子基因有显着连接的候选基因结合。这种扩展的疾病模块将确定较大的潜在靶标和药物。我们使用了在Covex中实施的紧密中心性算法来寻找新的靶标和可再利用的药物。通过网络医学方法,我们提供了疾病的机械观点,并指出了新的药物和靶标。结论:我们证明,系统和网络医学方法是理解疾病并理解其行动机制的有力方法。

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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