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基于多種分子水平數(shù)據(jù)識別肥厚型心肌病的重要生物標(biāo)志物及功能分析

發(fā)布時間:2018-06-20 00:42

  本文選題:肥厚型心肌病 + miRNA; 參考:《電子科技大學(xué)》2017年碩士論文


【摘要】:肥厚型心肌病(hypertrophic cardiomyopathy, HCM)是一種以心肌非對稱性肥厚且不伴有心室(一般為左心室)內(nèi)腔擴大為特征的家族性心臟疾病,嚴(yán)重患者可能并發(fā)室性心律失常、房顫、心力衰竭及心源性猝死等,但其致病機制不詳。因此,揭示HCM的致病機制,識別其重要生物標(biāo)志物,對其診斷和治療具有重要的科學(xué)與臨床意義。隨著分子生物學(xué)理論和技術(shù)的發(fā)展,國內(nèi)外對HCM致病的分子機制研究有了較大的進展并取得了一定成果,但是研究的分子相對單一和局限,沒能從分子間相互作用的網(wǎng)絡(luò)層次去系統(tǒng)地研究其致病機制,已識別的重要生物標(biāo)志物也比較有限。因此本文采用圖論、復(fù)雜網(wǎng)絡(luò)理論以及生物信息學(xué)的方法和手段,構(gòu)建HCM相關(guān)的miRNA-mRNA-lncRNA三元混合網(wǎng)絡(luò);通過分析網(wǎng)絡(luò)的拓?fù)涮卣骱蛥?shù),識別HCM的重要標(biāo)志物并分析其生物功能。本文的研究主要內(nèi)容如下:(1)構(gòu)建HCM相關(guān)的miRNA-mRNA-lncRNA混合網(wǎng)絡(luò)。首先整理HCM的lncRNA、mRNA和miRNA表達譜數(shù)據(jù),包括去除空值和重復(fù)值等;然后,用T檢驗加倍數(shù)法篩選出顯著差異表達的lncRNA、mRNA和miRNA;接著,設(shè)計lncRNA、mRNA和miRNA三元混合網(wǎng)絡(luò)構(gòu)建方法,用差異表達的lncRNA、mRNA和miRNA構(gòu)建HCM的miRNA-mRNA-lncRNA混合網(wǎng)絡(luò)。最后,采用復(fù)雜網(wǎng)絡(luò)理論驗證該混合網(wǎng)絡(luò)的生物屬性。(2)基于miRNA-mRNA-lncRNA混合網(wǎng)絡(luò)特征,篩選HCM相關(guān)的重要標(biāo)志物。根據(jù)節(jié)點的中心性測度介數(shù)、度以及緊密度排序,分別篩選網(wǎng)絡(luò)的重要節(jié)點,獲得HCM相關(guān)的重要lncRNA、mRNA和miRNA。(3)采用GO、KEGG和GeneCards等生物信息學(xué)工具并結(jié)合相關(guān)工作,分析HCM相關(guān)的重要lncRNA、mRNA和miRNA的功能,解釋HCM致病的分子機制。
[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.
【學(xué)位授予單位】:電子科技大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2017
【分類號】:R542.2

【參考文獻】

相關(guān)期刊論文 前1條

1 金國珍;周子慧;陳紹良;劉志忠;徐兢;;經(jīng)皮室間隔化學(xué)消融術(shù)治療肥厚型梗阻性心肌病80例臨床分析[J];中國心血管雜志;2013年05期



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