Bioinformatic identification of key pathways, hub genes, and microbiota for therapeutic intervention inHelicobacter pyloriinfection

Bioinformatic identification of key pathways, hub genes, and microbiota for therapeutic intervention inHelicobacter pyloriinfection
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幽门螺杆菌感染治疗干预的关键途径、中心基因和微生物群的生物信息识别

DOI:
10.1002/jcp.29925
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发表时间:
2020-07-24
影响因子:
5.6
通讯作者:
Fan,Hongying
Fan,Hongying
中科院分区:
生物学2区
文献类型:
--
作者:
Chen,Zhenhui;Chen,Huijuan;Fan,Hongying

文献摘要

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幽门螺杆菌感染的致病机制仍有待明确,潜在的干预微生物群刚刚开始被识别。在本研究中,使用基因集富集分析(GSEA)来整合 ThreeH。幽门螺杆菌感染微阵列数据集来自基因表达综合数据库,并确定了健康个体和幽门螺杆菌感染个体之间存在差异的 10 个标志性基因集和 35 个京都基因和基因组百科全书 (KEGG) 途径。对两个数据集进行加权基因共表达网络分析(WGCNA),确定了三个关键基因共表达模块。这些模块包含 54 个富集的 KEGG 通路,其中 25 个与 GSEA 分析重叠,表明在 H.幽门螺杆菌感染。我们从三个关键模块中选择了 116 个枢纽基因,使用 H.幽门螺杆菌悉尼菌株 1 并基于 20 个粘膜样本和序列读取存档数据集验证了微生物组 80.WGCNA 的上调,揭示了与幽门螺杆菌相关的四个微生物群模块。幽门螺杆菌感染。负相关模块包含 11 个微生物组家族。这些发现为H. 的发病机制提供了新的见解。幽门螺杆菌感染并系统地鉴定了 25 个关键途径、80 个上调的中枢基因和 11 个候选干预微生物家族以供进一步研究。
The pathogenic mechanisms ofHelicobacter pyloriinfection remain to be defined, and potential interventional microbiota are just beginning to be identified. In this study, gene‐set enrichment analysis (GSEA) was used to integrate threeH. pyloriinfection microarray data sets from the gene expression omnibus database and identified ten hallmark gene sets and 35 Kyoto encyclopedia of genes and genomes (KEGG) pathways that differed between healthy andHelicobacter pylori‐infected individuals. Weighted gene co‐expression network analysis (WGCNA) performed on two of the data sets identified three key gene coexpression modules. These modules contained 54 enriched KEGG pathways, 25 of which overlapped with the GSEA analysis, suggesting potentially important roles inH. pylori‐infection. We selected 116 hub genes from the three key modules for in vitro validation at the transcriptional level usingH. pyloriSydney Strain 1 and verified the upregulation of 80. WGCNA of the microbiomes based on 20 mucosal samples and a sequence read archive data set revealed four microbiota modules correlated withH. pyloriinfection. The negatively correlated modules contained 11 microbiome families. These findings provide new insight into the pathogenesis ofH. pyloriinfection and systematically identify 25 key pathways, 80 upregulated hub genes, and 11 families of candidate interventional microbiota for further research.