基于GEO骨髓增生异常综合征芯片数据的生物信息学分析

Bioinformatics Analysis of Microarray Data in Myelodysplastic Syndrome Based on Gene Expression Omnibus Database

目的:用生物信息学分析方法挖掘骨髓增生异常综合征的关键基因并探索其发病机制。方法:从公共基因芯片数据库(GEO)中下载2组骨髓增生异常综合征表达谱芯片数据,通过GEO2R工具在线分析,筛选出骨髓增生异常综合征中差异表达基因,利用GO数据库获取差异表达基因的功能注释,利用KEGG数据库进行通路富集分析,基于STRING数据库利用MCC算法筛选具有高度连接性的关键基因。结果:经差异分析得到差异表达基因112个,其中上调基因85个,下调基因27个。GO富集结果显示,生物学过程主要富集于免疫反应等,细胞成分富集于细胞膜等,分子功能富集于蛋白结合等。KEGG信号通路结果显示,主要的基因富集通路有原发性免疫缺陷、造血细胞系、B细胞受体信号通路、Hippo信号通路、哮喘。Cytoscape软件MCODE插件共筛选出显著模块3个,基于STRING数据库型筛选出CD19、CD79A、CD79B、EBF1、VPREB1、IRF4、BLNK、RAG1、POU2AF1、IRF8这10个蛋白相互作用网络中的关键节点基因。结论:筛选出的关键基因和信号通路有助于加深对骨髓增生异常综合征发病分子机制的理解,同时为临床靶向治疗的研究提供一定的理论依据。

Objective: To identify the key genes and explore mechanisms in the development of myelodysplastic syndrome(MDS) by bioinformatics analysis. Methods: Two cohorts profile datasets of MDS were downloaded from Gene Expression Omnibus(GEO) database. Differentially expressed gene(DEG) was screened by GEO2 R, functional annotation of DEG was gained from GO database, gene ontology(GO) enrichment analysis was performed via Kyoto Encyclopedia of Genes and Genomes(KEGG) database, and key genes were screened by Matthews correlation coefficient(MCC) based on STRING database. Results: There were 112 DEGs identified, including 85 up-regulated genes and 27 down-regulated genes. GO enrichment analysis showed that biological processes were mainly enriched in immune response, etc, cellular component in cell membrane, etc, and molecular function in protein binding, etc. KEGG signaling pathway analysis showed that main gene enrichment pathways were primary immunodeficiency, hematopoietic cell lineage, B cell receptor signaling pathway, Hippo signaling pathway, and asthma. Three significant modules were screened by Cytoscape software MCODE plug-in, while 10 key node genes(CD19, CD79 A, CD79 B, EBF1, VPREB1, IRF4, BLNK, RAG1, POU2 AF1, IRF8) in protein-protein interaction(PPI) network were screened based on STRING database. Conclusion: These screened key genes and signaling pathways are helpful to better understand molecular mechanism of MDS, and provide theoretical basis for clinical targeted therapy.