摘要
目的通过生物信息学方法分析肾移植术后BK病毒相关性肾病(BKVAN)的核心基因及其与浸润的免疫细胞相关性。方法从美国国立生物技术信息中心基因表达综合数据库下载BKVAN相关数据集GSE75693和GSE72925,BK病毒(BKV)血症相关数据集GSE47199。合并GSE75693和GSE72925后筛选差异表达基因(DEGs),然后进行基因本体生物过程(GOBP)以及京都基因与基因组百科全书(KEGG)通路分析,并通过蛋白-蛋白相互作用(PPI)网络进一步筛选核心基因。使用CIBERSORT进行免疫浸润分析,然后计算差异的免疫细胞和核心基因的相关性。最后,在GSE47199数据集筛选BKV血症和BKVAN共同的核心基因,使用基因集富集分析(GSEA)鉴定共同的核心基因分别在BKVAN和BKV血症中的生物过程。所有统计分析及可视化均基于R语言(4.0.2)。P<0.05为差异有统计学意义。结果在合并数据中共筛选出175个上调及70个下调DEGs。在PPI网络中,通过5种方法交集得到9个核心基因,核心基因主要富集在免疫细胞活化与功能相关的进程;在KEGG分析中,核心基因主要富集在病毒蛋白与细胞因子和细胞因子受体间相互作用、细胞因子-细胞因子受体间相互作用以及趋化因子信号通路等。免疫浸润分析表明PTPRC、CCL5、TYROBP、CXCL10、CD2和CXCL9与BKVAN中浸润的免疫细胞相关。CD2是BKVAN和BKV血症的共同核心基因。结论通过生物信息学方法筛选出BKVAN的核心基因,其中PTPRC、CCL5、TYROBP、CXCL10、CD2和CXCL9与BKVAN中浸润的免疫细胞相关,CD2是BKVAN和BKV血症的共同核心基因,这些标志物为肾移植术后BKVAN的诊治提供依据。
Objective To analyze hub genes in BK virus-associated nephropathy(BKVAN)after renal transplantation and its relationship with infiltrating immune cells by bioinformatics methods.Methods GSE75693 and GSE72925(BKVAN-related datasets)and GSE47199(a BK viremia-related dataset)were downloaded from GEO database.Then GSE75693 and GSE72925 were combined to screen for differential expression genes(DEGs),followed by gene ontology biological process(BPGO),Kyoto encyclopedia of genes and genomes(KEGG)pathway and protein-protein interaction(PPI)network analysis to further screen hub genes.Immune infiltration analysis was performed using CIBERSORT,and then correlations between differential immune cells and hub genes were calculated.Finally,common hub genes in both BK viremia and BKVAN were screened in the GSE47199 dataset,and the biological process of common hub genes in BKVAN and BK viremia were identified using gene set enrichment analysis(GSEA).All statistical analysis and visualizations were based on R language(4.0.2).P<0.05 was considered statistically significant.Results A total of 175 up-regulated and 70 down-regulated DEGs were screened from the combined dataset.Nine hub genes were obtained from the PPI network by five methods of intersection,and the hub genes were mainly enriched in the processes related to immune cell activation and function;in the KEGG analysis,the hub genes were mainly enriched in viral proteins,cytokine and cytokine receptor interactions,cytokine-cytokine receptor interactions and chemokine signaling pathways.Immune infiltration analysis showed that PTPRC,CCL5,TYROBP,CXCL10,CD2 and CXCL9 were associated with infiltrating immune cells in BKVAN.CD2 was the common hub gene for both BKVAN and BK viremia.Conclusions In this study,the hub genes of BKVAN were screened by bioinformatics,among which PTPRC,CCL5,TYROBP,CXCL10,CD2 and CXCL9 were associated with immune cells infiltration in BKVAN,and CD2 was the common hub gene of BKVAN and BK viremia.
作者
董博清
豆猛
张静
冯新顺
郑瑾
李潇
丁小明
薛武军
李杨
Boqing Dong;Meng Dou;Jing Zhang;Xinshun Feng;Jin Zheng;Xiao Li;Xiaoming Ding;Wujun Xue;Yang Li(Department of Kidney Transplantation,First Affiliated Hospital&Institute of Organ Transplantation,Xi′an Jiaotong University,Xi′an 710061,China)
出处
《中华移植杂志（电子版）》
CAS
2022年第4期201-209,共9页
Chinese Journal of Transplantation(Electronic Edition)
基金
陕西省重点研发计划(2022SF-148)
西安交通大学基本科研业务基金(xzy012021060)
中国器官移植发展基金课题。
