基于多种分子水平数据识别肥厚型心肌病的重要生物标志物及功能分析

发布时间：2018-06-20 00:42

本文选题：肥厚型心肌病 + miRNA　；参考：《电子科技大学》2017年硕士论文

【摘要】：肥厚型心肌病(hypertrophic cardiomyopathy, HCM)是一种以心肌非对称性肥厚且不伴有心室(一般为左心室)内腔扩大为特征的家族性心脏疾病,严重患者可能并发室性心律失常、房颤、心力衰竭及心源性猝死等,但其致病机制不详。因此,揭示HCM的致病机制,识别其重要生物标志物,对其诊断和治疗具有重要的科学与临床意义。随着分子生物学理论和技术的发展,国内外对HCM致病的分子机制研究有了较大的进展并取得了一定成果,但是研究的分子相对单一和局限,没能从分子间相互作用的网络层次去系统地研究其致病机制,已识别的重要生物标志物也比较有限。因此本文采用图论、复杂网络理论以及生物信息学的方法和手段,构建HCM相关的miRNA-mRNA-lncRNA三元混合网络;通过分析网络的拓扑特征和参数,识别HCM的重要标志物并分析其生物功能。本文的研究主要内容如下:(1)构建HCM相关的miRNA-mRNA-lncRNA混合网络。首先整理HCM的lncRNA、mRNA和miRNA表达谱数据,包括去除空值和重复值等;然后,用T检验加倍数法筛选出显著差异表达的lncRNA、mRNA和miRNA;接着,设计lncRNA、mRNA和miRNA三元混合网络构建方法,用差异表达的lncRNA、mRNA和miRNA构建HCM的miRNA-mRNA-lncRNA混合网络。最后,采用复杂网络理论验证该混合网络的生物属性。(2)基于miRNA-mRNA-lncRNA混合网络特征,筛选HCM相关的重要标志物。根据节点的中心性测度介数、度以及紧密度排序,分别筛选网络的重要节点,获得HCM相关的重要lncRNA、mRNA和miRNA。(3)采用GO、KEGG和GeneCards等生物信息学工具并结合相关工作,分析HCM相关的重要lncRNA、mRNA和miRNA的功能,解释HCM致病的分子机制。
[Abstract]:Hypertrophic cardiomyopathy (HCM) is a familial heart disease characterized by asymmetric hypertrophy of the myocardium without the enlargement of the ventricle (usually left ventricle). The severe patients may be complicated with ventricular arrhythmias, atrial fibrillation, heart failure and sudden cardiac death, but the pathogenesis is unknown. So HCM is undisclosed. The pathogenesis and identification of its important biomarkers are of great scientific and clinical significance for the diagnosis and treatment of them. With the development of molecular biology theory and technology, the molecular mechanism of HCM has been progresses at home and abroad, and some achievements have been made. The interacted network level studies its pathogenic mechanism, and the important biomarkers are also limited. Therefore, this paper uses graph theory, complex network theory and the methods and means of bioinformatics to construct a HCM related miRNA-mRNA-lncRNA three element hybrid network; by analyzing the topological features and parameters of the network, the identification of the network is identified. HCM's important biomarkers and their biological functions are analyzed. The main contents of this paper are as follows: (1) construct a HCM related miRNA-mRNA-lncRNA hybrid network. Firstly, the lncRNA, mRNA and miRNA expression data of HCM, including the removal of the empty value and the repetition value, are removed, and then the T test doubling method is used to screen out the significantly different expressions of lncRNA, mRNA and miRNA; Then, design lncRNA, mRNA and miRNA three element hybrid network construction methods, construct HCM's miRNA-mRNA-lncRNA hybrid network with differentially expressed lncRNA, mRNA and miRNA. Finally, the complex network theory is used to verify the biological properties of the hybrid network. (2) based on the characteristics of miRNA-mRNA-lncRNA mixed network, the important markers related to HCM are screened. The central measure, degree and tightness of point measure, select important nodes of the network, obtain important HCM related lncRNA, mRNA and miRNA. (3) use GO, KEGG and GeneCards bioinformatics tools and combine relevant work to analyze the functions of HCM related important lncRNA, mRNA and miRNA, and explain the molecular mechanism of HCM.
【学位授予单位】：电子科技大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R542.2

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