神经源性异位骨化相关差异基因的筛选及生物信息学分析

Identification and Bioinformatics Analysis of Differential Genes Related to Neurogenic Heterotopic Ossification

目的:基于GEO数据库筛选神经源性异位骨化的差异基因并进行生物信息学分析,寻找疾病相关基因和通道。方法:从GEO数据库中下载关于神经源性异位骨化的基因表达谱芯片,通过R软件的Limma包以调整后的P<0.05和|Log2(fold-change)|>2作为阈值筛选异位骨化组和健康对照组的差异基因,使用Matascape在线工具对差异基因进行GO富集及KEGG通路富集分析,并构建差异基因蛋白质-蛋白质相互作用关系(PPI)网络,利用Cytohubba和MCODE算法寻找关键基因。结果:共筛选出276个差异基因,其中上调基因150个,下调基因126个,差异表达基因的生物学过程(BP)主要在化学突触传递、跨突触信号的调控、骨化等过程富集;分子功能(MF)主要在细胞外基质结构成分、肝素结合、糖胺聚糖结合富集;细胞成分(CC)主要在胶原三聚体、含胶原蛋白的细胞外基质、细胞外基质富集。KEGG信号通路分析主要富集在补体和凝血级联、IL-17、Wnt、蛋白的消化吸收等通路。PPI网络共鉴别出EGF、GPR18、ADRA2C、CXCL1、C3、CXCL6、ADRB2、PENK、CXCL2、CDH1共10个hub基因和CXCL2、PTH2、EPHB1、HTR2B共4个种子基因。结论:通过对基因芯片的生物信息学分析,发现了可能与神经源性异位骨化相关的基因及分子调控机制。

Objective:To identify the differential expressed genes of neurogenic heterotopic ossification(NHO)based on GEO database and analyze them by bioinformatics to find the disease-related genes and channels.Methods:Download the gene expression microarray about NHO from GEO database.The differential genes of NHO group and healthy control group were screened by Limma package of R Software with the thresholds of adj.P-value<0.05 and|Log 2(fold-change)|>2.The differential genes were enriched by GO and KEGG pathway by Matascape online tool,and the network of protein-protein interaction(PPI)of differential genes was constructed.Cytohubba and Mcode algorithms were used to find the key genes.Results:A total of 276 differential genes were screened,including 150 up-regulated genes and 126 down-regulated genes.The biological process(BP)of differentially expression genes was mainly enriched in modulation of chemical synaptic transmission,regulation of trans-synaptic signaling and ossification.Molecular function(MF)was mainly enriched in extracellular matrix structural constituent,heparin binding and glycosaminoglycan binding.The cellular component(CC)was mainly enriched in collagen trimer,collagen-containing extracellular matrix and extracellular matrix.KEEG signal pathway analysis was mainly enriched in complement and coagulation cascade,IL-17 signal pathway,Wnt signal pathway,protein digestion and absorption and so on.Ten hub genes including EGF,GPR18,ADRA2 C,CXCL1,C3,CXCL6,ADRB2,PENK,CXCL2,CDH1 and four seed genes including CXCL2,PTH2,EPHB1,HTR2 B were identified in PPI network.Conclusion:Through the bioinformatics analysis of the gene microarray,we found the genes and molecular regulation mechanisms that may be related to NHO.