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利用多个数据集确定脑出血中自噬相关分子机制

The use of multiple datasets to identify autophagy-related molecular mechanisms in intracerebral hemorrhage.

作者信息

Xiao Yinggang, Zhang Yang, Wang Cunjin, Ge Yali, Gao Ju, Huang Tianfeng

机构信息

Department of Anesthesiology, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, China.

Department of Anesthesiology, Yangzhou University Affiliated Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, China.

出版信息

Front Genet. 2023 Apr 3;14:1032639. doi: 10.3389/fgene.2023.1032639. eCollection 2023.

Abstract

Intracerebral hemorrhage (ICH) is a stroke syndrome with high mortality and disability rates, but autophagy's mechanism in ICH is still unclear. We identified key autophagy genes in ICH by bioinformatics methods and explored their mechanisms. We downloaded ICH patient chip data from the Gene Expression Omnibus (GEO) database. Based on the GENE database, differentially expressed genes (DEGs) for autophagy were identified. We identified key genes through protein-protein interaction (PPI) network analysis and analyzed their associated pathways in Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Gene-motif rankings, miRWalk and ENCORI databases were used to analyze the key gene transcription factor (TF) regulatory network and ceRNA network. Finally, relevant target pathways were obtained by gene set enrichment analysis (GSEA). Eleven autophagy-related DEGs in ICH were obtained, and , , and were identified as key genes with clinical predictive value by PPI and receiver operating characteristic (ROC) curve analysis. The candidate gene expression level was significantly correlated with the immune infiltration level, and most of the key genes were positively correlated with the immune cell infiltration level. The key genes are mainly related to cytokine and receptor interactions, immune responses and other pathways. The ceRNA network predicted 8,654 interaction pairs (24 miRNAs and 2,952 lncRNAs). We used multiple bioinformatics datasets to identify , , and as key genes that contribute to the development of ICH.

摘要

脑出血(ICH)是一种死亡率和致残率都很高的中风综合征,但自噬在脑出血中的机制仍不清楚。我们通过生物信息学方法鉴定了脑出血中的关键自噬基因,并探讨了它们的机制。我们从基因表达综合数据库(GEO)下载了脑出血患者芯片数据。基于GENE数据库,鉴定出自噬相关的差异表达基因(DEGs)。我们通过蛋白质-蛋白质相互作用(PPI)网络分析鉴定关键基因,并在基因本体论(GO)和京都基因与基因组百科全书(KEGG)中分析它们的相关通路。利用基因基序排名、miRWalk和ENCORI数据库分析关键基因转录因子(TF)调控网络和ceRNA网络。最后,通过基因集富集分析(GSEA)获得相关的靶通路。获得了11个脑出血中与自噬相关的DEGs,通过PPI和受试者工作特征(ROC)曲线分析,鉴定出 、 、 和 为具有临床预测价值的关键基因。候选基因表达水平与免疫浸润水平显著相关,且大多数关键基因与免疫细胞浸润水平呈正相关。关键基因主要与细胞因子和受体相互作用、免疫反应等通路相关。ceRNA网络预测了8654个相互作用对(24个miRNA和2952个lncRNA)。我们使用多个生物信息学数据集,鉴定出 、 、 和 为促成脑出血发生发展的关键基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aada/10106621/86008c1667b9/fgene-14-1032639-g001.jpg

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