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Discovery of Bladder Cancer-related Genes Using Integrative Heterogeneous Network Modeling of Multi-omics Data

机译:使用多组学数据的综合异构网络建模发现膀胱癌相关基因

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摘要

In human health, a fundamental challenge is the identification of disease-related genes. Bladder cancer (BC) is a worldwide malignant tumor, which has resulted in 170,000 deaths in 2010 up from 114,000 in 1990. Moreover, with the emergence of multi-omics data, more comprehensive analysis of human diseases become possible. In this study, we propose a multi-step approach for the identification of BC-related genes by using integrative Heterogeneous Network Modeling of Multi-Omics data (iHNMMO). The heterogeneous network model properly and comprehensively reflects the multiple kinds of relationships between genes in the multi-omics data of BC, including general relationships, unique relationships under BC condition, correlational relationships within each omics and regulatory relationships between different omics. Besides, a network-based propagation algorithm with resistance is utilized to quantize the relationships between genes and BC precisely. The results of comprehensive performance evaluation suggest that iHNMMO significantly outperforms other approaches. Moreover, further analysis suggests that the top ranked genes may be functionally implicated in BC, which also confirms the superiority of iHNMMO. In summary, this study shows that disease-related genes can be better identified through reasonable integration of multi-omics data.
机译:在人类健康中,一项基本挑战是疾病相关基因的鉴定。膀胱癌(BC)是一种世界范围的恶性肿瘤,从1990年的114,000例死亡到2010年导致170,000例死亡。此外,随着多组学数据的出现,对人类疾病的更全面分析成为可能。在这项研究中,我们提出了一种通过使用多组学数据的综合异构网络建模(iHNMMO)来识别BC相关基因的多步骤方法。异构网络模型正确,全面地反映了BC多组学数据中基因之间的多种关系,包括一般关系,BC条件下的独特关系,每个组中的相关关系以及不同组之间的调控关系。此外,利用具有抗性的基于网络的传播算法来精确地定量基因和BC之间的关系。综合性能评估的结果表明,iHNMMO明显优于其他方法。此外,进一步的分析表明,排名最高的基因可能在功能上与BC有关,这也证实了iHNMMO的优越性。总而言之,这项研究表明,通过合理整合多组学数据可以更好地识别与疾病相关的基因。

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