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通过生物信息学分析研究可能的扩张型心肌病靶点。

Investigating possible dilated cardiomyopathy targets via bioinformatic analysis.

作者信息

Zhou Jun, Wang Xueting, Xiong Weiping, Zhang Min

机构信息

Division of Cardiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.

Department of Cardiovascular Medicine, Liqun Hospital Putuo District, Shanghai, China.

出版信息

Am J Transl Res. 2023 Jul 15;15(7):4788-4795. eCollection 2023.

Abstract

Dilated cardiomyopathy (DCM) is the most common cardiomyopathy associated with heart failure; however, the underlying mechanism remains unclear. Initially, gene expression data of patients with DCM from the GSE4172 and GSE21610 datasets were obtained from the Gene Expression Omnibus website. Differentially expressed genes (DEGs) were analyzed with a false discovery rate < 0.05 and log2 fold change > 1.2. Furthermore, both the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Set Enrichment Analysis (GSEA) were used to investigate the functional annotations. STRING and Cytoscape tools were used to form the protein-protein interaction (PPI) network and authenticate hub genes. Thereafter, the signature of immune-related genes (IRGs) was selected from the DEGs and data via the IMMPORT website. Hub genes were selected from the differentially expressed IRGs that formed the PPI network. Finally, the receiver-operating characteristic curves of the key genes were measured as biomarkers of DCM. A total of 173 independent DEGs (103 upregulated and 70 downregulated genes) were found in the microarray datasets GSE4172 and GSE21610. KEGG analysis and GSEA indicated that the BMP signaling pathway and apoptosis-related signals have a key effect on DCM development. The 10 hub genes also indicated the key effect of the BMP signaling pathway on DCM. A total of 224 differentially expressed IRGs and 20 featured IRGs were identified. Finally, and were identified as possible targets for DCM. Our data suggest a possible molecular regulatory mechanism for DCM therapy. Moreover, and may have key effects on the development of DCM.

摘要

扩张型心肌病(DCM)是与心力衰竭相关的最常见的心肌病;然而,其潜在机制仍不清楚。最初,从基因表达综合数据库网站获取了来自GSE4172和GSE21610数据集的DCM患者的基因表达数据。使用错误发现率<0.05且log2倍数变化>1.2来分析差异表达基因(DEG)。此外,京都基因与基因组百科全书(KEGG)分析和基因集富集分析(GSEA)均用于研究功能注释。使用STRING和Cytoscape工具构建蛋白质-蛋白质相互作用(PPI)网络并鉴定枢纽基因。此后,通过IMMPORT网站从DEG和数据中选择免疫相关基因(IRG)的特征。从形成PPI网络的差异表达IRG中选择枢纽基因。最后,测量关键基因的受试者工作特征曲线作为DCM的生物标志物。在微阵列数据集GSE4172和GSE21610中总共发现了173个独立的DEG(103个上调基因和70个下调基因)。KEGG分析和GSEA表明,骨形态发生蛋白(BMP)信号通路和凋亡相关信号对DCM的发展具有关键作用。这10个枢纽基因也表明BMP信号通路对DCM具有关键作用。总共鉴定出224个差异表达的IRG和20个特征性IRG。最后,[此处原文缺失两个基因名称]被确定为DCM的可能靶点。我们的数据提示了一种可能的DCM治疗分子调控机制。此外,[此处原文缺失两个基因名称]可能对DCM的发展具有关键作用。

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KLF13 Loss-of-Function Mutations Underlying Familial Dilated Cardiomyopathy.家族性扩张型心肌病的 KLF13 功能丧失突变。
J Am Heart Assoc. 2022 Nov 15;11(22):e027578. doi: 10.1161/JAHA.122.027578. Epub 2022 Nov 8.

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