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用于缺血性中风和代谢综合征的整合单细胞RNA测序与孟德尔随机化研究

Integrated single cell-RNA sequencing and Mendelian randomization for ischemic stroke and metabolic syndrome.

作者信息

Li Jie, Shen Sen, Yu Cong, Sun Shuchen, Zheng Ping

机构信息

Department of Neurosurgery, Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Department of Neurosurgery, Shanghai Pudong New area People's Hospital, Shanghai, China.

出版信息

iScience. 2024 Jun 11;27(7):110240. doi: 10.1016/j.isci.2024.110240. eCollection 2024 Jul 19.

Abstract

Although more and more evidence has supported that metabolic syndrome (MS) is linked to ischemic stroke (IS), the molecular mechanism and genetic association between them has not been investigated. Here, we combined the existing single-cell RNA sequencing (scRNA-seq) data and mendelian randomization (MR) for stroke to understand the role of dysregulated metabolism in stroke. The shared hub genes were identified with machine learning and WGCNA. A total of six upregulated DEGs and five downregulated genes were selected for subsequent analyses. Nine genes were finally identified with random forest, Lasso regression, and XGBoost method as a potential diagnostic model. scRNA-seq also show the abnormal glycolysis level in most cell clusters in stroke and associated with the expression level of hub genes. The genetic relationship between IS and MS was verified with MR analysis. Our study reveals the common molecular profile and genetic association between ischemic stroke and metabolic syndrome.

摘要

尽管越来越多的证据支持代谢综合征(MS)与缺血性中风(IS)有关,但它们之间的分子机制和遗传关联尚未得到研究。在此,我们结合现有的单细胞RNA测序(scRNA-seq)数据和中风的孟德尔随机化(MR)分析,以了解代谢失调在中风中的作用。通过机器学习和加权基因共表达网络分析(WGCNA)确定了共享的枢纽基因。总共选择了6个上调的差异表达基因(DEGs)和5个下调基因进行后续分析。最终通过随机森林、套索回归和XGBoost方法确定了9个基因作为潜在的诊断模型。scRNA-seq还显示中风中大多数细胞簇的糖酵解水平异常,且与枢纽基因的表达水平相关。通过MR分析验证了IS与MS之间的遗传关系。我们的研究揭示了缺血性中风与代谢综合征之间的共同分子特征和遗传关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13a8/11253530/35c09b20c29b/fx1.jpg

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