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运用整合生物信息学方法和机器学习策略来识别心房颤动的潜在特征。

Using integrative bioinformatics approaches and machine-learning strategies to identify potential signatures for atrial fibrillation.

作者信息

Fu Shihao, Feng Zian, Li Ao, Ma Zhenxiao, Zhang Haiyang, Zhao Zhiwei

机构信息

Department of Cardiovascular Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.

Department of Cardiology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China.

出版信息

Int J Cardiol Heart Vasc. 2025 Jan 2;56:101592. doi: 10.1016/j.ijcha.2024.101592. eCollection 2025 Feb.

Abstract

Atrial fibrillation (AF) is the most common tachyarrhythmia and seriously affects human health. Key targets of AF bioinformatics analysis can help to better understand the pathogenesis of AF and develop therapeutic targets. The left atrial appendage tissue of 20 patients with AF and 10 patients with sinus rhythm were collected for sequencing, and the expression data of the atrial tissue were obtained. Based on this, 2578 differentially expressed genes were obtained through differential analysis. Different express genes (DEGs) were functionally enriched on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), mainly focusing on neuroactive ligand-receptor interactions, neuronal cell body pathways, regulation of neurogenesis, and neuronal death, regulation of neuronal death, etc. Secondly, 14 significant module genes were obtained by analyzing the weighted gene co-expression network of DEGs. Next, LASSO and SVM analyzes were performed on the differential genes, and the results were in good agreement with the calibration curve of the nomogram model for predicting AF constructed by the weighted gene co-expression network key genes. The significant module genes obtained by the area under the ROC curve (AUC) analysis were analyzed. Through crossover, two key disease characteristic genes related to AF, HOXA2 and RND2, were screened out. RND2 was selected for further research, and qPCR verified the expression of RND2 in sinus rhythm patients and AF patients. Patients with sinus rhythm were significantly higher than those in AF patients. Our research indicates that RND2 is significantly associated with the onset of AF and can serve as a potential target for studying its pathogenesis.

摘要

心房颤动(AF)是最常见的快速性心律失常,严重影响人类健康。AF生物信息学分析的关键靶点有助于更好地理解AF的发病机制并开发治疗靶点。收集20例AF患者和10例窦性心律患者的左心耳组织进行测序,获得心房组织的表达数据。在此基础上,通过差异分析获得2578个差异表达基因。差异表达基因(DEGs)在基因本体论(GO)和京都基因与基因组百科全书(KEGG)上进行功能富集,主要集中在神经活性配体-受体相互作用、神经元细胞体通路、神经发生调控、神经元死亡调控等方面。其次,通过分析DEGs的加权基因共表达网络获得14个显著模块基因。接下来,对差异基因进行LASSO和支持向量机(SVM)分析,结果与由加权基因共表达网络关键基因构建的预测AF的列线图模型的校准曲线吻合良好。对通过ROC曲线(AUC)分析获得的显著模块基因进行分析。通过交叉分析,筛选出两个与AF相关的确切疾病特征基因,即HOXA2和RND2。选择RND2进行进一步研究,qPCR验证了RND2在窦性心律患者和AF患者中的表达。窦性心律患者的表达明显高于AF患者。我们的研究表明,RND2与AF的发病显著相关,可作为研究其发病机制的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ddd/11754484/bb0941044973/gr1.jpg

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