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鉴定呼吸道合胞病毒感染细胞外免疫反应中潜在的免疫/诊断相关基因-免疫细胞亚群网络。

Identification of potential immune/diagnosis related gene-immunocyte subtype networks in extracellular immune response to respiratory syncytial virus infection.

机构信息

Department of Pediatrics, Yantai Yuhuangding Hospital, No.20, East Road Yuhuangding, Zhifu District, Yantai, Shandong 264000, PR China.

Department of Pediatrics, Yantai Yuhuangding Hospital, No.20, East Road Yuhuangding, Zhifu District, Yantai, Shandong 264000, PR China.

出版信息

Virus Res. 2022 Nov;321:198906. doi: 10.1016/j.virusres.2022.198906. Epub 2022 Aug 28.

Abstract

INTRODUCTION

Respiratory syncytial virus (RSV) is one of the important pathogenic agents of pediatric respiratory tract infection. Weighted gene co-expression network analysis (WGCNA) is used to study autoimmune diseases, which can find potential hub genes. The diagnostic model based on hub genes and machine learning makes it possible to diagnose the extracellular immune response to RSV infection early.

OBJECTIVE

The aim of the present study was to identify potential immune, diagnose and treatment related genes expressed in RSV-infected cells.

METHODS

Firstly, gene expression data were downloaded from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs). Secondly, WGCNA was performed based on DEGs to obtain hub genes related to immunity score. Thirdly, protein-protein interaction (PPI) and the immune infiltration analysis of hub immune related genes were performed. Finally, diagnostic and immune related genes were identified by machine learning, followed by functional analysis.

RESULTS

Totally, 2063 DEGs were identified in the extracellular immune response to RSV infection. Among which, 10 key immune and diagnosis related genes were identified, including ITGA2B, GP9, ITGB3, SELP, PPBP, MPL, CXCL8, NFE2, PTGS1 and LY6G6F. Several immune/diagnosis related gene-immunocyte subtype networks were identified, such as CXCL8-Type 17 T helper cell, LY6G6F-CD56 bright natural killer cell, PPBP-activated CD4 T cell/T follicular helper cell, NFE2/PTGS1/SELP-activated dendritic cell, GP9/ITGA2B/MPL-activated CD8 T cell. ITGB3, MPL and PTGS1 could be considered as therapeutic targets. Some significantly enriched signaling pathways were identified, including hematopoietic cell lineage (involving GP9 and ITGA2B), cytokine-cytokine receptor interaction (involving MPL), chemokine signaling pathway (involving PPBP) and arachidonic acid metabolism (involving PTGS1).

CONCLUSIONS

The 10-immune related gene signature may be used as potential diagnostic markers for the extracellular immune response to RSV infection, which may provide a new field in searching for diagnostic and therapeutic molecules in the extracellular immune response to RSV infection.

摘要

简介

呼吸道合胞病毒(RSV)是儿科呼吸道感染的重要致病因子之一。加权基因共表达网络分析(WGCNA)用于研究自身免疫性疾病,可以找到潜在的枢纽基因。基于枢纽基因和机器学习的诊断模型使得早期诊断 RSV 感染的细胞外免疫反应成为可能。

目的

本研究旨在鉴定 RSV 感染细胞中表达的潜在免疫、诊断和治疗相关基因。

方法

首先,从基因表达综合数据库(GEO)下载基因表达数据,以鉴定差异表达基因(DEGs)。其次,基于 DEGs 进行 WGCNA,以获得与免疫评分相关的枢纽基因。然后,进行蛋白质-蛋白质相互作用(PPI)和枢纽免疫相关基因的免疫浸润分析。最后,通过机器学习鉴定诊断和免疫相关基因,并进行功能分析。

结果

总共鉴定出 2063 个 RSV 感染细胞外免疫反应的 DEGs。其中,鉴定出 10 个关键的免疫和诊断相关基因,包括 ITGA2B、GP9、ITGB3、SELP、PPBP、MPL、CXCL8、NFE2、PTGS1 和 LY6G6F。鉴定出几个免疫/诊断相关基因-免疫细胞亚型网络,如 CXCL8-Type 17 T 辅助细胞、LY6G6F-CD56 明亮自然杀伤细胞、PPBP-激活的 CD4 T 细胞/T 滤泡辅助细胞、NFE2/PTGS1/SELP-激活的树突状细胞、GP9/ITGA2B/MPL-激活的 CD8 T 细胞。ITGB3、MPL 和 PTGS1 可被视为治疗靶点。鉴定出一些显著富集的信号通路,包括造血细胞谱系(涉及 GP9 和 ITGA2B)、细胞因子-细胞因子受体相互作用(涉及 MPL)、趋化因子信号通路(涉及 PPBP)和花生四烯酸代谢(涉及 PTGS1)。

结论

10-免疫相关基因特征可作为 RSV 感染细胞外免疫反应的潜在诊断标志物,为寻找 RSV 感染细胞外免疫反应的诊断和治疗分子提供了新领域。

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