• 中文核心期刊
  • CSCD来源期刊
  • 中国科技核心期刊
  • CA、CABI、ZR收录期刊

基于生物信息学筛选小鹅瘟差异表达基因及潜在治疗中药预测

Bioinformatics analysis of differentially expressed genes in gosling plague and prediction of potential therapeutic Chinese medicine

  • 摘要:
    目的 通过生物信息学方法筛选小鹅瘟(gosling plague, GP)相关数据集的致病核心基因及主要信号通路,预测潜在治疗靶点和有效干预中药。
    方法 通过收集GeneCards数据库中GP相关靶点并经Uniprot数据库标准化,并提取基因表达综合数据库(gene expression omnibus, GEO)肠道炎症数据集(GSE14841)和营养不良数据集(GSE43698),合并使用R语言Limmar包来筛选GP的差异表达基因(differentially expressed genes, DEGs)。利用DAVID数据库对DEGs进行基因本体论(Gene Ontology, GO)分析以及京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes, KEGG)富集分析,通过STRING数据库构建蛋白互作网络(protein-protein interaction network, PPI),Cytoscape 软件及其插件筛选子网络核心基因。将核心基因与Coremine Medical数据库相互映射,筛选能够治疗GP的潜在中药。
    结果 共筛选得到58个DEGs,富集分析结果显示,DEGs主要参与宿主细胞膜受体识别病毒蛋白、细胞质水解酶与转移酶活性等生物过程,定位于‌肌动蛋白细胞骨架(actin cytoskeleton, AC),环鸟苷酸-腺苷酸合成酶和干扰素基因刺激因子(cytosolic DNA-Sensing and the STING, cGAS-STING)、丝裂原活化蛋白激酶(mitogen-activated protein kinase, MARK)与Toll样受体(toll-like receptor, TLR)信号通路。通过PPI鉴定出Degree值前10名关键基因:干扰素诱导螺旋酶C结构域3(interferon induced with helicase C domain 3, IFIH3)、干扰素诱导螺旋酶C结构域1(interferon induced with helicase C domain 1, IFIH1)、线粒体抗病毒信号蛋白(mitochondrial antiviral signaling protein, MAVS)、C-C趋化因子配体5(C-C motif chemokine ligand 5, CCL5)、Toll样受体4(toll-like receptor 4, TLR4)、核因子κB(nuclear factor-kappa B, NF-κB)、Ras相关C3毒素底物2(ras-related C3 botulinum toxin substrate 2, RAC2)、Toll样受体9(toll-like receptor 9, TLR9)、早期生长应答基因1(early growth response 1, EGR1)、Erb-B2受体酪氨酸激酶3(erb-B2 receptor tyrosine kinase 3, ERBB3)。TLR4TLR9NF-κBERBB3为筛选到的GP感染性炎症4个核心基因。预测出治疗GP的潜在中药50种,中药类别主要包括清热解毒药、补虚药、解表药、收敛止泻药等4类。
    结论 本研究应用生物信息学方法明确了与GP相关的4个核心基因以及50种潜在靶向中药,为防治GP的天然药物研发提供了新思路与理论依据。

     

    Abstract:
    Objective By using bioinformatics methods, we screened the core pathogenic genes and main signaling pathways of GP from related datasets, and predicted potential therapeutic targets and effective intervention Chinese herbal medicines.
    Method GP-related targets were collected from the GeneCards database and standardized via the Uniprot database. The intestinal inflammation dataset (GSE14841) and the malnutrition dataset (GSE43698) from the Gene Expression Omnibus (GEO) were extracted and combined. The differentially expressed genes (DEGs) of GP were screened using the Limma package in R language. The DAVID database was used for GO analysis and KEGG enrichment analysis of DEGs. The STRING database was used to construct the protein-protein interaction network (PPI), and the Cytoscape software and its plugins were used to screen the core genes of the sub-network. The core genes were mapped with the Coremine Medical database to screen for potential traditional Chinese medicines that could treat GP.
    Result A total of 58 DEGs were screened out. The results of enrichment analysis showed that the DEGs were mainly involved in biological processes such as the recognition of viral proteins by the host cell membrane receptors, and the activities of cytoplasmic hydrolases and transferases. They were located in the actin cytoskeleton (AC), the cytosolic DNA-Sensing and the STING (cGAS-STING), mitogen-activated protein kinase (MARK) and toll-like receptor (TLR) signaling pathways. Through the PPI, the top 10 key genes in terms of the Degree value were identified: interferon induced with helicase C domain 3 (IFIH3), interferon induced with helicase C domain 1 (IFIH1), mitochondrial antiviral signaling protein (MAVS), C-C motif chemokine ligand 5 (CCL5), toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), ras-related C3 botulinum toxin substrate 2 (RAC2), toll-like receptor 9 (TLR9), early growth response 1 (EGR1), erb-B2 receptor tyrosine kinase 3 (ERBB3). TLR4, TLR9, NF-κB and ERBB3 were the four core genes identified in the inflammatory response to GP infection. A total of 50 potential traditional Chinese medicines for treating GP were predicted, and the categories of traditional Chinese medicines mainly included four types such as heat-clearing and detoxifying medicines, tonifying deficiency medicines, exterior-releasing medicines, and astringent antidiarrheal medicines.
    Conclusion This study applied bioinformatics methods to identify four core genes related to GP and 50 potential targeted traditional Chinese medicines, providing new ideas and theoretical basis for the development of natural medicines for the prevention and treatment of GP.

     

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