通过加权基因共表达网络分析和机器学习识别并验证原发性开角型青光眼中的氧化应激相关基因

IF 1.3 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Medicine Pub Date : 2024-11-15 DOI:10.1097/MD.0000000000040389
Lu-Qian Yang, Yue Song, Feng Huang, Wei Wu, Hong-Pei Ji
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引用次数: 0

摘要

原发性开角型青光眼(POAG)是一种常见的眼科疾病,目前还没有有效的治疗方法来治疗 POAG。因此,找出一些有效的诊断标志物有利于患者的治疗。表达谱来自基因表达总库(GEO)数据库。利用基因本体论、京都基因和基因组百科全书以及基因组富集分析对功能富集进行了分析。利用加权基因共表达网络分析(WGCNA)确定了共表达基因。通过拉索回归(Lasso regression)、支持向量机递归特征消除(SVM-RFE)和随机森林(Random Forest)筛选枢纽基因,并使用接收者操作特征曲线评估诊断价值。免疫细胞浸润用 IOBR 软件包计算。通过 STRING、miRactDB 和 Cytoscape 构建调控网络。使用 oncoPredict 软件包预测候选化疗药物。根据 GSE27276 数据库,确定了 541 个差异表达基因。利用WGCNA和机器学习确定了5个具有高曲线下面积值的氧化应激相关基因,即HBB、MAOA、ACOX2、ALDH7A1和TYMP。与正常组相比,POAG 组的 NK 细胞、CD4 T 细胞和树突状细胞的浸润水平明显增加,而 CD8 T 细胞和 Tregs 细胞则明显减少。HBB与大多数免疫细胞密切相关。16个miRNA靶向了所有枢纽基因。药物敏感性分析表明,一些药物对POAG更敏感,如Acetalax_1804、Ibrutinib_1799和OSI_027_1594。我们发现 5 个氧化应激相关基因对 POAG 具有较高的诊断价值。
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Identification and validation of oxidative stress-related genes in primary open-angle glaucoma by weighted gene co-expression network analysis and machine learning.

Primary open-angle glaucoma (POAG) is a common ocular disease, and there is currently no effective treatment for POAG therapy. Thus, identifying some effective diagnostic markers is beneficial to the treatment of patients. The expression profile was obtained from Gene Expression Omnibus (GEO) database. The functional enrichment was analyzed using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and gene set enrichment analysis. Co-expressed genes were identified using weighted gene co-expression network analysis (WGCNA). Hub genes were screened through Lasso regression, support vector machine-recursive feature elimination (SVM-RFE) and Random Forest, and receiver operating characteristic curve was used to assess diagnostic value. Immune cell infiltration was calculated using IOBR package. The regulatory network was constructed through STRING, miRactDB and Cytoscape. The oncoPredict package was employed to predict the candidate chemotherapy agents. According to GSE27276 database, 541 differentially expressed genes were identified. Five oxidative stress-related genes with high area under the curve value, namely HBB, MAOA, ACOX2, ALDH7A1 and TYMP, were determined using WGCNA and machine learning. Infiltration level of NK cells, CD4 T cells and dendritic cells were significantly increased in POAG group compared with normal group, while CD8 T cells and Tregs cells were significantly decreased. HBB was closely related to most immune cells. Hub genes were all targeted by 16 miRNAs. Drug sensitivity analysis exhibited that some drugs were more sensitivity for POAG, such as Acetalax_1804, Ibrutinib_1799 and OSI_027_1594. We identified 5 oxidative stress-related genes with high diagnostic value for POAG.

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来源期刊
Medicine
Medicine 医学-医学:内科
CiteScore
2.80
自引率
0.00%
发文量
4342
审稿时长
>12 weeks
期刊介绍: Medicine is now a fully open access journal, providing authors with a distinctive new service offering continuous publication of original research across a broad spectrum of medical scientific disciplines and sub-specialties. As an open access title, Medicine will continue to provide authors with an established, trusted platform for the publication of their work. To ensure the ongoing quality of Medicine’s content, the peer-review process will only accept content that is scientifically, technically and ethically sound, and in compliance with standard reporting guidelines.
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