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基于机器学习的帕金森病中铜中毒相关生物标志物及免疫浸润特征分析

Machine learning-based characterization of cuprotosis-related biomarkers and immune infiltration in Parkinson's disease.

作者信息

Zhao Songyun, Zhang Li, Ji Wei, Shi Yachen, Lai Guichuan, Chi Hao, Huang Weiyi, Cheng Chao

机构信息

Department of Neurosurgery, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China.

Department of Neurology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China.

出版信息

Front Genet. 2022 Oct 17;13:1010361. doi: 10.3389/fgene.2022.1010361. eCollection 2022.

Abstract

Parkinson's disease (PD) is a neurodegenerative disease commonly seen in the elderly. On the other hand, cuprotosis is a new copper-dependent type of cell death that can be observed in various diseases. This study aimed to identify potential novel biomarkers of Parkinson's disease by biomarker analysis and to explore immune cell infiltration during the onset of cuprotosis. Gene expression profiles were retrieved from the GEO database for the GSE8397, GSE7621, GSE20163, and GSE20186 datasets. Three machine learning algorithms: the least absolute shrinkage and selection operator (LASSO), random forest, and support vector machine-recursive feature elimination (SVM-RFE) were used to screen for signature genes for Parkinson's disease onset and cuprotosis-related genes (CRG). Immune cell infiltration was estimated by ssGSEA, and cuprotosis-related genes associated with immune cells and immune function were examined using spearman correlation analysis. Nomogram was created to validate the accuracy of these cuprotosis-related genes in predicting PD disease progression. Classification of Parkinson's specimens using consensus clustering methods. Three PD datasets from the Gene Expression Omnibus (GEO) database were combined after eliminating batch effects. By ssGSEA, we identified three cuprotosis-related genes ATP7A, SLC31A1, and DBT associated with immune cells or immune function in PD and more accurate for the diagnosis of Parkinson's disease course. Patients could benefit clinically from a characteristic line graph based on these genes. Consistent clustering analysis identified two subtypes, with the C2 subtype exhibiting higher immune cell infiltration and immune function. In conclusion, our study reveals that several newly identified cuprotosis-related genes intervene in the progression of Parkinson's disease through immune cell infiltration.

摘要

帕金森病(PD)是一种常见于老年人的神经退行性疾病。另一方面,铜死亡是一种新发现的依赖铜的细胞死亡类型,可在多种疾病中观察到。本研究旨在通过生物标志物分析确定帕金森病潜在的新型生物标志物,并探讨铜死亡发生过程中的免疫细胞浸润情况。从基因表达综合数据库(GEO数据库)中检索了GSE8397、GSE7621、GSE20163和GSE20186数据集的基因表达谱。使用三种机器学习算法:最小绝对收缩和选择算子(LASSO)、随机森林和支持向量机递归特征消除法(SVM-RFE)筛选帕金森病发病的特征基因和铜死亡相关基因(CRG)。通过单样本基因集富集分析(ssGSEA)估计免疫细胞浸润情况,并使用斯皮尔曼相关分析检测与免疫细胞和免疫功能相关的铜死亡相关基因。创建列线图以验证这些铜死亡相关基因在预测帕金森病疾病进展方面的准确性。使用一致性聚类方法对帕金森病样本进行分类。消除批次效应后,将来自基因表达综合数据库(GEO)的三个帕金森病数据集进行合并。通过ssGSEA,我们确定了三个与帕金森病中免疫细胞或免疫功能相关的铜死亡相关基因ATP7A、SLC31A1和DBT,它们对帕金森病病程的诊断更准确。基于这些基因的特征线图可为患者提供临床益处。一致性聚类分析确定了两个亚型,其中C2亚型表现出更高的免疫细胞浸润和免疫功能。总之,我们的研究表明,几个新发现的铜死亡相关基因通过免疫细胞浸润干预帕金森病的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2e5/9629507/1c5833e09ec9/fgene-13-1010361-g001.jpg

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