本文選題：DCM + RCM��； 參考：《電子科技大學(xué)》2017年碩士論文

【摘要】：心血管疾病一直都是威脅全人類健康的復(fù)雜疾病,而心肌病在心血管疾病的發(fā)病中占據(jù)了重要的位置,并且有著逐年上升的趨勢。心肌病又分為繼發(fā)性心肌病與原發(fā)性心肌病,繼發(fā)性心肌病的病因多數(shù)已經(jīng)清楚,而原發(fā)性心肌病的病因迄今為止尚未明確。本文所研究的擴(kuò)張型心肌病(Dilated cardiomyopathy,DCM)和限制型心肌病(Restrictive cardiomyopathy,RCM)都屬于原發(fā)性心肌病。其中,DCM的發(fā)病率占心肌病的發(fā)病率80%以上,并且心肌病患者中有58.3%死于該病。RCM發(fā)病率雖然僅占心肌病發(fā)病率的4.5%,然而它是原發(fā)性心肌病中最嚴(yán)重的一種類型,并且其預(yù)后性很差。因此,對于這兩類心肌疾病發(fā)生發(fā)展機制的研究工作刻不容緩。轉(zhuǎn)錄組作為連接基因組遺傳信息與蛋白質(zhì)組生物功能的紐帶,相比于基因組,它更具備時間性和空間性,因此被廣泛地應(yīng)用于醫(yī)學(xué)、病理學(xué)和藥學(xué)等相關(guān)領(lǐng)域。隨著二代測序技術(shù)成本的降低,使得轉(zhuǎn)錄組測序被大規(guī)模地應(yīng)用于生物學(xué)與醫(yī)學(xué)研究中。本文通過對DCM和RCM的RNA-Seq數(shù)據(jù)進(jìn)行挖掘,旨在對這兩類原發(fā)性心肌疾病的發(fā)生發(fā)展機制進(jìn)行研究和探索,為兩類心肌病的精確診斷、及時控制以及治療預(yù)后等提供一些新思路。本文的主要研究內(nèi)容如下:(1)采用標(biāo)準(zhǔn)化的RNA-Seq數(shù)據(jù)處理方法,包括質(zhì)量控制(Fast QC)、參考序列比對(Tophat)、計數(shù)數(shù)據(jù)的轉(zhuǎn)換(HTSeq)、歸一化(EDASeq)和差異表達(dá)(DESeq),篩選和識別出分別與DCM、RCM相關(guān)的差異表達(dá)基因。對于DCM,篩選出451個相關(guān)的差異表達(dá)基因;對于RCM,篩選出1326個相關(guān)的差異表達(dá)基因。(2)分別用DCM和RCM相關(guān)的差異表達(dá)基因構(gòu)建共表達(dá)網(wǎng)絡(luò)。通過對共表達(dá)網(wǎng)絡(luò)作網(wǎng)絡(luò)特征分析,找出與疾病相關(guān)的關(guān)鍵節(jié)點基因,即疾病可能的基因標(biāo)志物。對每種疾病的基因標(biāo)志物進(jìn)行生物功能分析,并對其在疾病發(fā)生發(fā)展中的作用進(jìn)行闡釋。(3)從生物功能和信號通路的角度,對DCM和RCM的基因標(biāo)志物進(jìn)行比較,為從分子層面上區(qū)分兩類心肌病提供一些新思路。
[Abstract]:Cardiovascular disease has always been a complex disease threatening the health of mankind. Cardiomyopathy occupies an important position in the incidence of cardiovascular disease and has a rising trend year by year. Cardiomyopathy is divided into secondary cardiomyopathy and primary cardiomyopathy. Both dilated cardiomyopathy (DCM) and restricted cardiomyopathy (RCM) are primary cardiomyopathy. The incidence of DCM accounts for more than 80% of the incidence of cardiomyopathy, and 58.3% of the patients with cardiomyopathy died of the disease. Although the incidence of RCM is only 4.5% of the incidence of cardiomyopathy, it is the most serious type of primary cardiomyopathy. And its prognosis is very poor. Therefore, it is urgent to study the development mechanism of these two kinds of myocardial diseases. As a link between genomic genetic information and proteome biological function, transcriptome is more temporal and spatial than genome, so it has been widely used in medicine, pathology, pharmacy and other related fields. With the reduction of the cost of second generation sequencing, transcriptome sequencing has been widely used in biological and medical research. By mining the RNA-Seq data of DCM and RCM, this paper aims to study and explore the mechanism of the occurrence and development of these two kinds of primary myocardial diseases, and to provide some new ideas for the accurate diagnosis, timely control and treatment and prognosis of the two kinds of cardiomyopathy. The main contents of this paper are as follows: (1) A standardized RNA-Seq data processing method is used. It includes quality control fast QCN, reference sequence alignment, Tophata, conversion of counting data, normalized EDASeqand differential expression, and screening and identification of differentially expressed genes associated with DCMN RCM respectively. For DCM, 451 differentially expressed genes were screened. For RCM, 136 differentially expressed genes were screened. By analyzing the network characteristics of coexpression networks, we find out the key node genes related to disease, that is, the possible gene markers of disease. The biomarkers of each disease were analyzed, and their role in the development of the disease was explained. (3) from the perspective of biological function and signal pathway, the genetic markers of DCM and RCM were compared. It provides some new ideas for differentiating two kinds of cardiomyopathy from the molecular level.
【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

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