二叶式主动脉瓣钙化关键基因的生物信息学分析

朱鹏程; 张倩; 卞金辉; 章辉; 倪布清; 邵永丰

doi:10.7619/jcmp.20211339

二叶式主动脉瓣钙化关键基因的生物信息学分析

Bioinformatics analysis of hub genes for bicuspid aortic valve calcification

摘要

摘要:
目的采用生信分析技术探讨二叶式主动脉瓣(BAV)钙化相关的关键基因(hub基因)。
方法从Gene Expression Omnibus (GEO)数据库中下载BAV相关的基因表达矩阵及临床数据，应用Perl及R软件筛选出钙化的BAV与正常主动脉瓣的差异基因(DEGs)，通过R软件对DEGs进行富集分析，使用Cytoscape构建蛋白质互作(PPI)网络。使用Degree算法计算并取排名前10的DEGs作为hub基因，分别采用miRWalk数据库及FunRich软件预测hub基因对应的microRNA并取交集，构建miRNA-mRNA调控网络。
结果从数据集GSE83453中共筛选出DEGs 126个，其中上调基因85个，下调基因41个。通过PPI网络计算出10个hub基因，并由此预测出12个上游miRNA。
结论 BAV瓣膜钙化通路可能与三叶式主动脉瓣瓣膜钙化相似，与其相关的hub基因是SPP1和MMP9。加剧BAV瓣膜病变并导致BAV相关并发症的hub基因可能是THBS2、COL5A2、COL4A1、COL1A1、COL3A1、COL4A2、COL1A2、SERPINE1。

Abstract:
Objective To explore the hub genes associated with bicuspid aortic valve (BAV) calcification by bioinformatics analysis.
Methods The BAV-related gene expression matrix and clinical data were downloaded from Gene Expression Omnibus (GEO) database. Differential genes (DEGs) between calcified BAV and normal aortic valve were screened by Perl and R software. DEGs was performed enrichment analysis by R software, and protein-protein interaction (PPI) network was constructed by Cytoscape. The degree algorithm was used to calculate and take the top 10 DEGs as hub genes. The miRWalk database and FunRich software were used to predict the corresponding microRNA of hub genes and obtain the intersection, and thus the miRNA-mRNA regulatory network was constructed.
Results A total of 126 DEGs were screened from dataset GSE83453, including 85 up-regulated DEGs and 41 down-regulated DEGs. Totally 10 hub genes were calculated from PPI network and 12 upstream miRNAs were predicted by the hub genes.
Conclusion The pathway of BAV calcification may be similar to that of trefoil aortic valve calcification, and the associated hub genes are SPP1 and MMP9. The possible hub genes exacerbating BAV valve disease and leading BAV-related complications are THBS2, COL5A2, COL4A1, COL1A1, COL3A1, COL4A2, COL1A2 and SERPINE1.

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