A network-based approach to uncover microRNA-mediated disease comorbidities and potential pathobiological implications.,npj Systems Biology and Applications

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A network-based approach to uncover microRNA-mediated disease comorbidities and potential pathobiological implications.
npj Systems Biology and Applications ( IF 3.5 ) Pub Date : 2019-11-13 , DOI: 10.1038/s41540-019-0115-2
Shuting Jin ₁ , Xiangxiang Zeng ₂ , Jiansong Fang ₃ , Jiawei Lin ₁ , Stephen Y Chan ₄ , Serpil C Erzurum _{5,

6} , Feixiong Cheng _{3,

7,

8}

Affiliation

Disease-disease relationships (e.g., disease comorbidities) play crucial roles in pathobiological manifestations of diseases and personalized approaches to managing those conditions. In this study, we develop a network-based methodology, termed meta-path-based Disease Network (mpDisNet) capturing algorithm, to infer disease-disease relationships by assembling four biological networks: disease-miRNA, miRNA-gene, disease-gene, and the human protein-protein interactome. mpDisNet is a meta-path-based random walk to reconstruct the heterogeneous neighbors of a given node. mpDisNet uses a heterogeneous skip-gram model to solve the network representation of the nodes. We find that mpDisNet reveals high performance in inferring clinically reported disease-disease relationships, outperforming that of traditional gene/miRNA-overlap approaches. In addition, mpDisNet identifies network-based comorbidities for pulmonary diseases driven by underlying miRNA-mediated pathobiological pathways (i.e., hsa-let-7a- or hsa-let-7b-mediated airway epithelial apoptosis and pro-inflammatory cytokine pathways) as derived from the human interactome network analysis. The mpDisNet offers a powerful tool for network-based identification of disease-disease relationships with miRNA-mediated pathobiological pathways.

中文翻译：

一种基于网络的方法来揭示 microRNA 介导的疾病合并症和潜在的病理生物学影响。

疾病与疾病之间的关系（例如，疾病合并症）在疾病的病理生物学表现和管理这些病症的个性化方法中发挥着至关重要的作用。在这项研究中，我们开发了一种基于网络的方法，称为基于元路径的疾病网络（mpDisNet）捕获算法，通过组装四个生物网络来推断疾病与疾病的关系：疾病-miRNA、miRNA-基因、疾病-基因、和人类蛋白质-蛋白质相互作用组。 mpDisNet 是一种基于元路径的随机游走，用于重建给定节点的异构邻居。 mpDisNet使用异构skip-gram模型来解决节点的网络表示。我们发现 mpDisNet 在推断临床报告的疾病-疾病关系方面表现出很高的性能，优于传统的基因/miRNA 重叠方法。此外，mpDisNet 还识别了由潜在 miRNA 介导的病理生物学途径（即 hsa-let-7a 或 hsa-let-7b 介导的气道上皮细胞凋亡和促炎细胞因子途径）驱动的基于网络的肺部疾病合并症，源自人类相互作用组网络分析。 mpDisNet 提供了一个强大的工具，用于通过 miRNA 介导的病理生物学途径基于网络识别疾病之间的关系。

更新日期：2019-11-13

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