变应性鼻炎特异性病毒应答相关基因的生物信息学分析

Bioinformatics analysis of genes associated with specific viral response to allergic rhinitis

摘要:

目的 变应性鼻炎（AR）患者感染鼻病毒后病情及气道炎症加重，但其分子机制尚未完全阐明。本研究通过生物信息学方法分析双链RNA （dsRNA）刺激后AR鼻黏膜上皮细胞中特异的基因表达特征。方法 基于GEO数据库的GSE51392数据集，利用R语言的Limma函数筛选出dsRNA刺激后AR上皮细胞特异性差异表达基因（DEGs）。通过GO和KEGG进行通路富集分析，以确定这些基因参与的生物学过程及功能。此外，通过STRING数据库构建蛋白质相互作用（PPI）网络，并使用Cytoscape寻找AR特异性的hub基因和集簇。结果 共筛选出545个上调和400个下调的AR特异性DEGs，包括上调基因PPBP/CXCL7和下调基因IL20、BLNK、CEBPD、LY96。通过GO和KEGG分析，我们发现dsRNA刺激后AR与健康对照受试者（HC）上皮相比具有不同的功能和信号通路。此外，AR特异性的DEGs构建了由791个节点和603条连线组成的PPI网络。并利用MCODE从该PPI网络中筛选出PPBP/CXCL7等16个hub基因和5个重要集簇。结论 本研究通过生物信息学对数据进行挖掘并筛选出dsRNA刺激后AR特异性病毒应答相关基因，提示上调的hub基因以及下调的IL20、BLNK、CEBPD和LY96可能是鼻病毒诱发AR加重的重要因素。为下一步的研究提供参考。

Abstract:

Objective Allergic rhinitis (AR) patients infected with rhinovirus exhibit aggravated state of AR and airway inflammation. However, the mechanisms of airway inflammation exacerbated by RV are still largely unknown. This paper aims to detect the specific gene expression characteristics in AR nasal epithelium responding to double-stranded RNA (dsRNA) using bioinformatics analysis.Methods Bioinformatic tools were used to identify the differentially expressed genes (DEGs) specific in AR nasal epithelium responding to dsRNA based on the GSE51392 dataset retrieved from the Gene Expression Omnibus (GEO) database. DEGs were enriched by Gene ontology (GO) and the Kyoto encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. In addition, protein-protein interaction (PPI) network was constructed to find the key genes and modules specific to AR.Results From GSE51392 dataset, 545 up-regulated and 400 down-regulated AR-specific genes in nasal epithelium responding to dsRNA were identified, including up-regulated PPBP/CXCL7 and down-regulated IL20, BLNK, CEBPD, LY96. After GO and KEGG analyses, different functions and signaling pathways in nasal epithelium of AR compared to HC were revealed. In addition, the PPI network of DEGs was constructed, which was composed of 791 nodes and 603 edges. Sixteen genes with high degrees, including PPBP/CXCL7, were identified as hub genes, and 5 important modules were selected from PPI network using MCODE.Conclusion Our data indicate that up-regulated PPBP/CXCL7 and down-regulated IL20, BLNK, CEBPD, LY96 may be important contributors to RV induced AR exacerbation, which may help to understand the underlying mechanisms linking RV infection to AR exacerbation.