基于基因共表达网络分析的扩张和限制型心肌病分子特征比较

Comparisons Between Molecular Features of Dilated and Restrictive Cardiomyopathy Based on Gene Co-Expression Network Analysis

随着分子生物学的发展,两类原发性心肌病-扩张型心肌病(DCM)和限制型心肌病(RCM)的研究已取得一定的进展,但是两者的发病机制和病程发展过程的分子机理尚未明确,在临床上RCM很容易被误诊为DCM。因此,首先对两类心肌疾病的RNA-Seq转录组数据进行基因表达差异显著性分析,筛选出DCM相关的差异表达基因451个、RCM相关的差异表达基因1 326个;然后用两类心肌疾病相关的差异表达基因分别构建共表达网络,并基于网络特征找出两种心肌疾病相关的重要基因(即可能的基因标志物);接着对发现的DCM相关的21个基因标志物和RCM相关的65个基因标志物进行生物功能分析,阐释两类心肌疾病的一些发生发展机制;最后从基因标志物、生物功能和信号通路多个方面比较两类心肌疾病,为在分子水平上区分两类心肌疾病提供新思路。

With the development of molecular biology, the study on dilated cardiomyopathy（DCM） and restrictive cardiomyopathy（RCM） has been made much progress. However, the pathogenesis and molecular mechanism of progression of DCM and RCM are not yet clear. In clinic, RCM is easy to be misdiagnosed as DCM. This paper firstly made the difference significant analysis of RNA-Seq data for the two kinds of myocardial diseases, from which 451 and 1326 differentially expressed genes related to DCM and RCM were selected respectively. Then, the DCM and RCM co-expression networks were respectively constructed using their differentially expressed genes and the key nodes genes of the two classes of myocardial diseases were found based on the network features. Next, we performed biological function analysis for 21 and 65 genetic markers related to DCM and RCM respectively, and illustrated some important development mechanisms of the two kinds of myocardial diseases. Finally, DCM and RCM were compared from the angles of genetic markers, biological functions and signal pathways, which provided some new ideas about distinguishing DCM from RCM at molecular level.