Gao Yuan, Ding Li, Liu Jiang, Wang Xiaoyan, Meng Qiang
Department of Neurology, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming 650000, Yunnan, China.
Medicine School, Kunming University of Science and Technology, Kunming 650000, Yunnan, China.
Open Life Sci. 2023 Jun 22;18(1):20220622. doi: 10.1515/biol-2022-0622. eCollection 2023.
Essential tremor (ET) is a common neurological disorder with a difficult clinical diagnosis, primarily due to the lack of relevant biomarkers. The current study aims to identify possible biomarkers for ET by screening miRNAs using machine learning algorithms. In this investigation, public datasets and our own datasets were used to examine the ET disorder. The ET datasets originated from public sources. To generate our own dataset, high-throughput sequencing analyses were performed on ET and control samples from the First People's Hospital of Yunnan Province. Functional enrichment analysis was employed to identify the potential function of differentially expressed genes (DEGs). Using datasets from the Gene Expression Omnibus database, Lasso regression analysis and support vector machine recursive feature elimination were used to screen potential diagnostic genes for ET. To identify the genes responsible for the final diagnosis, area under the curves (AUCs) of the receiver operating characteristic was examined. Finally, an ssGSEA representing an ET immune landscape was created. The sample exhibited expression profiles that corresponded with six genes in the public database. Three diagnostic genes were discovered with AUCs >0.7 that can distinguish ET from normal data: APOE, SENP6, and ZNF148. Single-gene GSEA indicated that these diagnostic genes were closely associated with the cholinergic, GABAergic, and dopaminergic synapse networks. The immune microenvironment of ET was also affected by these diagnostic genes. According to the findings, these three DEGs (, , and ) may successfully differentiate between samples from ET patients and normal controls, serving as a helpful diagnostic tool. This effort provided a theoretical foundation for elucidating the pathogenesis of ET and raised hopes of overcoming the diagnostic difficulty of ET clinically.
特发性震颤(ET)是一种常见的神经系统疾病,临床诊断困难,主要原因是缺乏相关生物标志物。本研究旨在通过使用机器学习算法筛选微小RNA(miRNA)来确定ET可能的生物标志物。在这项调查中,使用公共数据集和我们自己的数据集来研究ET疾病。ET数据集来源于公共资源。为了生成我们自己的数据集,对云南省第一人民医院的ET样本和对照样本进行了高通量测序分析。采用功能富集分析来确定差异表达基因(DEG)的潜在功能。利用基因表达综合数据库中的数据集,采用套索回归分析和支持向量机递归特征消除法筛选ET的潜在诊断基因。为了确定最终诊断相关的基因,检测了受试者工作特征曲线下面积(AUC)。最后,创建了一个代表ET免疫景观的单样本基因集富集分析(ssGSEA)。该样本表现出与公共数据库中六个基因相对应的表达谱。发现了三个AUC>0.7的诊断基因,可将ET与正常数据区分开来:载脂蛋白E(APOE)、泛素特异性蛋白酶6(SENP6)和锌指蛋白148(ZNF148)。单基因基因集富集分析表明,这些诊断基因与胆碱能、γ-氨基丁酸能和多巴胺能突触网络密切相关。ET的免疫微环境也受到这些诊断基因的影响。根据研究结果,这三个差异表达基因(APOE、SENP6和ZNF148)可能成功区分ET患者样本和正常对照样本,可作为一种有用的诊断工具。这项工作为阐明ET的发病机制提供了理论基础,并提高了临床上克服ET诊断困难的希望。