【摘要】：房顫伴瓣膜性心臟病(Atrial fibrillation with valvular heart disease,AF-VHD)是一類瓣膜性疾病,易于引起一系列連鎖疾病的發(fā)生,比如心力衰竭、心肌梗塞、血栓等嚴重的并發(fā)癥,故具有非常高的傷害性以及致死率。隨著現(xiàn)代分子生物學理論和技術(shù)不斷的發(fā)展,國內(nèi)外對于AF-VHD的致病分子機制研究有了較大的發(fā)展,但是其研究角度相對單一,沒有從網(wǎng)絡(luò)的整體性去探尋疾病的致病機理。因此,本文結(jié)合數(shù)學網(wǎng)絡(luò)的篩選方法和生物信息分析的手段,分別構(gòu)建出瓣膜性心臟病(VHD)和AF-VHD兩種疾病的共調(diào)控網(wǎng)絡(luò),主要研究內(nèi)容為:(1)從已經(jīng)發(fā)表的文獻中收集到與VHD相關(guān)的15個mi RNAs,根據(jù)基因、miRNA、轉(zhuǎn)錄因子共調(diào)控網(wǎng)絡(luò)構(gòu)建方法,構(gòu)建VHD的混合共調(diào)控網(wǎng)絡(luò)。對網(wǎng)絡(luò)節(jié)點進行度篩選,找出了關(guān)鍵的4個miRNA、4個TF、31個基因,利用關(guān)鍵miRNA和靶基因進行GO功能富集分析和KEGG數(shù)據(jù)庫以及單獨解析34個基因的生物功能,映射到生物空間揭示VHD致病的分子機理。(2)基于本實驗室APCA靴帶抽樣方法提取的32個與AF-VHD疾病相關(guān)的miRNAs,利用與上一部分相同的網(wǎng)絡(luò)構(gòu)造方法原理,構(gòu)建出AF-VHD混合調(diào)控共網(wǎng)絡(luò)。通過網(wǎng)絡(luò)特征分析,篩選出關(guān)鍵的5個miRNA、5個TF、41個基因,映射到生物空間挖掘AF-VHD致病的分子機理。隨后對比VHD和AF-VHD兩者的網(wǎng)絡(luò),提取共同的生物特征進行分析,從而挖掘出其中的重要分子調(diào)節(jié)機制,闡述從VHD到AF-VHD疾病的發(fā)生發(fā)展病理機制。
[Abstract]:Atrial fibrillation with valvular heart disease (Atrial fibrillation with valvular heart disease,AF-VHD) is a kind of valvular disease, which is easy to cause a series of linked diseases, such as heart failure, myocardial infarction, thrombus and other serious complications. Therefore, it has very high toxicity and fatality rate. With the continuous development of modern molecular biology theory and technology, the research on the pathogenic molecular mechanism of AF-VHD has made great progress at home and abroad, but its research angle is relatively single, and it does not explore the pathogenic mechanism of the disease from the perspective of the integrity of the network. Therefore, combined with the screening method of mathematical network and the means of biological information analysis, the co-regulatory networks of (VHD) and AF-VHD of valvular heart disease were constructed, respectively. The main research contents are as follows: (1) 15 mi RNAs, related to VHD were collected from the published literature to construct a hybrid co-regulatory network of VHD according to the construction method of gene and miRNA, transcription factor co-regulatory network. Four key miRNA,4 TF,31 genes were identified by screening the network nodes. GO functional enrichment analysis, KEGG database and single analysis of the biological functions of 34 genes were carried out by using key miRNA and target genes. Mapping to biological space reveals the molecular mechanism of VHD pathogenicity. (2) based on the APCA bootstrap sampling method in our laboratory, 32 miRNAs, related to AF-VHD diseases are based on the same network construction method as the previous part. The co-network of AF-VHD hybrid regulation and control is constructed. Five key miRNA,5 TF,41 genes were screened and mapped to bio-space to explore the molecular mechanism of AF-VHD pathogenicity through network feature analysis. After comparing the networks of VHD and AF-VHD, the common biological characteristics were extracted for analysis, and the important molecular regulation mechanism was discovered. The pathogenesis of AF-VHD from VHD to AF-VHD was expounded.
【學位授予單位】：電子科技大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R541.75;R542.5
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本文編號：2474107