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通过LASSO和支持向量机算法筛选的帕金森病基因生物标志物

Parkinson's Disease Gene Biomarkers Screened by the LASSO and SVM Algorithms.

作者信息

Bao Yiwen, Wang Lufeng, Yu Fei, Yang Jie, Huang Dongya

机构信息

Tongji University School of Medicine, East Hospital, Department of Neurology, Tongji University, Shanghai 200070, China.

出版信息

Brain Sci. 2023 Jan 20;13(2):175. doi: 10.3390/brainsci13020175.

Abstract

Parkinson's disease (PD) is a common progressive neurodegenerative disorder. Various evidence has revealed the possible penetration of peripheral immune cells in the substantia nigra, which may be essential for PD. Our study uses machine learning (ML) to screen for potential PD genetic biomarkers. Gene expression profiles were screened from the Gene Expression Omnibus (GEO). Differential expression genes (DEGs) were selected for the enrichment analysis. A protein-protein interaction (PPI) network was built with the STRING database (Search Tool for the Retrieval of Interacting Genes), and two ML approaches, namely least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE), were employed to identify candidate genes. The external validation dataset further tested the expression degree and diagnostic value of candidate biomarkers. To assess the validity of the diagnosis, we determined the receiver operating characteristic (ROC) curve. A convolution tool was employed to evaluate the composition of immune cells by CIBERSORT, and we performed correlation analyses on the basis of the training dataset. Twenty-seven DEGs were screened in the PD and control samples. Our results from the enrichment analysis showed a close association with inflammatory and immune-associated diseases. Both the LASSO and SVM algorithms screened eight and six characteristic genes. AGTR1, GBE1, TPBG, and HSPA6 are overlapping hub genes strongly related to PD. Our results of the area under the ROC (AUC), including AGTR1 (AUC = 0.933), GBE1 (AUC = 0.967), TPBG (AUC = 0.767), and HSPA6 (AUC = 0.633), suggested that these genes have good diagnostic value, and these genes were significantly associated with the degree of immune cell infiltration. AGTR1, GBE1, TPBG, and HSPA6 were identified as potential biomarkers in the diagnosis of PD and provide a novel viewpoint for further study on PD immune mechanism and therapy.

摘要

帕金森病(PD)是一种常见的进行性神经退行性疾病。各种证据表明外周免疫细胞可能侵入黑质,这可能对帕金森病至关重要。我们的研究使用机器学习(ML)来筛选潜在的帕金森病基因生物标志物。从基因表达综合数据库(GEO)中筛选基因表达谱。选择差异表达基因(DEG)进行富集分析。使用STRING数据库(搜索相互作用基因的工具)构建蛋白质-蛋白质相互作用(PPI)网络,并采用两种机器学习方法,即最小绝对收缩和选择算子(LASSO)以及支持向量机递归特征消除(SVM-RFE)来识别候选基因。外部验证数据集进一步测试了候选生物标志物的表达程度和诊断价值。为了评估诊断的有效性,我们确定了受试者工作特征(ROC)曲线。使用卷积工具通过CIBERSORT评估免疫细胞的组成,并基于训练数据集进行相关性分析。在帕金森病和对照样本中筛选出27个差异表达基因。我们的富集分析结果表明与炎症和免疫相关疾病密切相关。LASSO和SVM算法均筛选出8个和6个特征基因。AGTR1、GBE1、TPBG和HSPA6是与帕金森病密切相关的重叠枢纽基因。我们的ROC曲线下面积(AUC)结果,包括AGTR1(AUC = 0.933)、GBE1(AUC = 0.967)、TPBG(AUC = 0.767)和HSPA6(AUC = 0.633),表明这些基因具有良好的诊断价值,并且这些基因与免疫细胞浸润程度显著相关。AGTR1、GBE1、TPBG和HSPA6被确定为帕金森病诊断中的潜在生物标志物,并为进一步研究帕金森病免疫机制和治疗提供了新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f0e/9953979/1b9c37112a32/brainsci-13-00175-g001.jpg

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