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基于生物信息学和机器学习方法筛选微小病变肾病的核心基因。

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

作者信息

Hao Dingfan, Yang Xiuting, Li Zexuan, Xie Bin, Feng Yongliang, Liu Gaohong, Ren Xiaojun

机构信息

Department of Epidemiology, School of Public Health, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, 030001, China.

Department of Nephrology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, No. 99 Longcheng Street, Taiyuan, 030032, Shanxi, China.

出版信息

Int Urol Nephrol. 2025 Feb;57(2):655-671. doi: 10.1007/s11255-024-04226-y. Epub 2024 Oct 9.

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.

摘要

基于生物信息学和机器学习方法,我们开展了一项研究,以筛选微小病变肾病(MCD)的核心基因,并进一步探究其发病机制。首先,我们从基因表达综合数据库(GEO)中获取了包含MCD信息的芯片数据集GSE108113和GSE200828。然后,我们使用R软件分析基因芯片数据,并进行功能富集分析。随后,我们利用Cytoscape筛选核心基因,并运用机器学习算法(随机森林和LASSO回归)对其进行准确识别。为了验证和分析核心基因,我们进行了免疫组织化学(IHC)和基因集富集分析(GSEA)。我们的结果显示共有394个高表达差异基因。富集分析表明,这些基因主要参与T细胞分化和免疫反应的p13k-akt信号通路。我们将NOTCH1、TP53、GATA3和TGF-β1鉴定为核心基因。IHC染色显示正常组和MCD组这四个核心基因的表达存在显著差异。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,我们的研究突出了NOTCH1、TP53、GATA3和TGF-β1作为MCD的核心基因,并强调了糖胺聚糖与MCD发病机制之间的密切关系。

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