Screening core genes for minimal change disease based on bioinformatics and machine learning approaches.

IF 1.8 4区 医学 Q3 UROLOGY & NEPHROLOGY International Urology and Nephrology Pub Date : 2025-02-01 Epub Date: 2024-10-09 DOI:10.1007/s11255-024-04226-y
Dingfan Hao, Xiuting Yang, Zexuan Li, Bin Xie, Yongliang Feng, Gaohong Liu, Xiaojun Ren
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Abstract

Based on bioinformatics and machine learning methods, we conducted a study to screen the core genes of minimal change disease (MCD) and further explore its pathogenesis. First, we obtained the chip data sets GSE108113 and GSE200828 from the Gene Expression Comprehensive Database (GEO), which contained MCD information. We then used R software to analyze the gene chip data and performed functional enrichment analysis. Subsequently, we employed Cytoscape to screen the core genes and utilized machine learning algorithms (random forest and LASSO regression) to accurately identify them. To validate and analyze the core genes, we conducted immunohistochemistry (IHC) and gene set enrichment analysis (GSEA). Our results revealed a total of 394 highly expressed differential genes. Enrichment analysis indicated that these genes are primarily involved in T cell differentiation and p13k-akt signaling pathway of immune response. We identified NOTCH1, TP53, GATA3, and TGF-β1 as the core genes. IHC staining demonstrated significant differences in the expression of these four core genes between the normal group and the MCD group. Furthermore, GSEA suggested that their up-regulation may be closely associated with the pathological changes in MCD kidneys, particularly in the glycosaminoglycans signaling pathway. In conclusion, our study highlights NOTCH1, TP53, GATA3, and TGF-β1 as the core genes in MCD and emphasizes the close relationship between glycosaminoglycans and pathogenesis of MCD.

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基于生物信息学和机器学习方法筛选最小变化疾病的核心基因。
基于生物信息学和机器学习方法,我们开展了一项研究,以筛选最小变化疾病(MCD)的核心基因并进一步探索其发病机制。首先,我们从基因表达综合数据库(GEO)中获得了包含MCD信息的芯片数据集GSE108113和GSE200828。然后,我们使用 R 软件分析了基因芯片数据,并进行了功能富集分析。随后,我们使用 Cytoscape 筛选核心基因,并利用机器学习算法(随机森林和 LASSO 回归)准确识别核心基因。为了验证和分析核心基因,我们进行了免疫组化(IHC)和基因组富集分析(GSEA)。结果显示,共有 394 个高表达差异基因。富集分析表明,这些基因主要参与了T细胞分化和免疫反应的p13k-akt信号通路。我们确定 NOTCH1、TP53、GATA3 和 TGF-β1 为核心基因。IHC 染色显示,这四个核心基因的表达在正常组和 MCD 组之间存在显著差异。此外,GSEA表明它们的上调可能与MCD肾脏的病理变化密切相关,尤其是在糖胺聚糖信号通路中。总之,我们的研究强调了NOTCH1、TP53、GATA3和TGF-β1是MCD的核心基因,并强调了糖胺聚糖与MCD发病机制的密切关系。
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来源期刊
International Urology and Nephrology
International Urology and Nephrology 医学-泌尿学与肾脏学
CiteScore
3.40
自引率
5.00%
发文量
329
审稿时长
1.7 months
期刊介绍: International Urology and Nephrology publishes original papers on a broad range of topics in urology, nephrology and andrology. The journal integrates papers originating from clinical practice.
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