房颤伴瓣膜性心脏病致病的混合调控网络构建与机理分析
发布时间：2019-05-11 00:16
【摘要】：房颤伴瓣膜性心脏病(Atrial fibrillation with valvular heart disease,AF-VHD)是一类瓣膜性疾病,易于引起一系列连锁疾病的发生,比如心力衰竭、心肌梗塞、血栓等严重的并发症,故具有非常高的伤害性以及致死率。随着现代分子生物学理论和技术不断的发展,国内外对于AF-VHD的致病分子机制研究有了较大的发展,但是其研究角度相对单一,没有从网络的整体性去探寻疾病的致病机理。因此,本文结合数学网络的筛选方法和生物信息分析的手段,分别构建出瓣膜性心脏病(VHD)和AF-VHD两种疾病的共调控网络,主要研究内容为:(1)从已经发表的文献中收集到与VHD相关的15个mi RNAs,根据基因、miRNA、转录因子共调控网络构建方法,构建VHD的混合共调控网络。对网络节点进行度筛选,找出了关键的4个miRNA、4个TF、31个基因,利用关键miRNA和靶基因进行GO功能富集分析和KEGG数据库以及单独解析34个基因的生物功能,映射到生物空间揭示VHD致病的分子机理。(2)基于本实验室APCA靴带抽样方法提取的32个与AF-VHD疾病相关的miRNAs,利用与上一部分相同的网络构造方法原理,构建出AF-VHD混合调控共网络。通过网络特征分析,筛选出关键的5个miRNA、5个TF、41个基因,映射到生物空间挖掘AF-VHD致病的分子机理。随后对比VHD和AF-VHD两者的网络,提取共同的生物特征进行分析,从而挖掘出其中的重要分子调节机制,阐述从VHD到AF-VHD疾病的发生发展病理机制。
[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.
【学位授予单位】：电子科技大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R541.75;R542.5
，
本文编号：2474107
[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.
【学位授予单位】：电子科技大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R541.75;R542.5
，
本文编号：2474107
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