非特异性间质性肺炎相关基因筛选和生物信息学分析

Screening and bioinformatics analysis of nonspecific interstitial pneumonia related genes

目的通过生物信息学的方法筛选非特异性间质性肺炎(nonspecific interstitial pneumonia,NSIP)的致病基因,为进一步研究提供靶点。方法从GEO数据库下载基因芯片数据集GSE110147、GSE21369、GSE40839,使用limma包分析工具筛选正常组织与NSIP的差异表达基因。通过clusterProfiler包对差异表达基因进行GO分析和KEGG通路富集分析,找到NSIP发病过程中差异表达基因主要参与的生物功能及其集中的信号通路。利用STRING数据库和CYTOSCAPE软件构建蛋白相互作用网络,使用MCODE软件提取蛋白相互作用网络中的子网络模块。结果3个数据集的差异表达基因做韦恩图得到3个共同差异表达基因。GO富集分析表明NSIP中上调的差异表达基因主要影响RNA剪接、抗病毒感染、对肽的细胞反应等相关的生物过程,富集的分子主要参与细胞组分的囊腔合成分泌、剪接复合体,富集的分子功能主要参与ATP酶活性,受体配体活性及DNA结合转录激活因子活性。NSIP中下调的蛋白主要涉及转移酶活性调节的生物过程。KEGG通路分析表明NSIP中上调的差异表达基因主要参与PI3K-Akt、人类乳头瘤病毒感染及MAPK等信号通路。结论利用生物信息学筛选出差异表达基因,可能是NSIP发病机制的新靶点,对诊断治疗NSIP具有临床意义。

Objective Screening the causative genes of nonspecific interstitial pneumonia(NSIP)by bioinformatics and provide targets for further research.Method By downloading the gene chip datasets GSE110147,GSE21369,GSE40839 from the GEO database,and using the limma package analysis tool to screen out the differentially expressed genes between normal tissues and NSIP.The clusterProfiler package was used to perform GO analysis and KEGG pathway enrichment analysis on the differentially expressed genes to find the biological functions of the differentially expressed genes and their concentrated signaling pathways in the pathogenesis of NSIP.To study the relationship between differentially expressed genes and proteins,the STRING database and CYTOSCAPE software were used to construct the protein-protein interaction(PPI)network,and the MCODE software was used to extract the sub-network modules in the protein interaction network.Result Veen plots result suggested three common significantly differentially expressed genes were found.GO enrichment analysis showed that up-regulated differentially expressed genes in NSIP mainly affected biological processes related to RNA splicing,antiviral infection,and cellular responses to peptides.The enriched molecules are mainly involved in the synthesis,secretion,and splicing complexes of cellular components,and the enriched molecular function are mainly involved in ATPase activity,receptor ligand activity and DNA-binding transcription activator activity.The down-regulated proteins in NSIP are mainly involved in biological processes regulated by transferase activity.KEGG pathway analysis showed that the up-regulated differentially expressed genes in NSIP were mainly involved in signaling pathways such as PI3K-Akt pathways,human papilloma virus infection pathways and MAPK pathways.Conclusion The differentially expressed genes screened by bioinformatics may be new targets for the pathogenesis of NSIP,which is significant for the future clinical diagnosis and treatment of NSIP.