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强直性脊柱炎治疗潜在靶基因的鉴定。

Identification of potential target genes for ankylosing spondylitis treatment.

作者信息

Ni Yong, Jiang Chengrui

机构信息

Department of Spine Surgery Department of Rheumatology and Immunology, Jining No.1 People's Hospital, Jining, Shandong Province, China.

出版信息

Medicine (Baltimore). 2018 Feb;97(8):e9760. doi: 10.1097/MD.0000000000009760.

Abstract

This study aimed to identify the potential target genes for the treatment of ankylosing spondylitis (AS).Dataset GSE25101 was downloaded from Gene Expression Omnibus, including 16 AS and 16 normal control blood samples. Differentially expressed genes (DEGs) were identified using unmatched t-test in limma package with adjusted P < .05. Gene ontology-biological process (GO-BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using multifaceted analysis tool for human transcriptome. Protein-protein interaction (PPI) network was constructed using STRING and Cytoscape, and module analysis was performed using MCODE plug-in. Webgestal was utilized to predict transcriptional factor (TF)-microRNA-target network and Comparative Toxicogenomics Database (CTD) was applied to predict chemical-target network.A total of 334 DEGs were identified, including 136 upregulated genes and 198 downregulated genes. According to STRING, a PPI network was constructed and 1 significant clustered module was screen out with score = 6.33. MAPK7 (degree = 11) and NDUFS4 (degree = 10) were 2 important nodes in PPI network, and both of them were significantly enriched in cAMP mediated signaling pathway (P = 2.02E-02). MAPK7 could be regulated by NFY. Both MAPK7 and NDUFS4 were 2 potential targets for Indomethacin.MAPK7 and NDUFS4 played important roles in the pathogenesis of AS via cAMP mediated signaling pathway. Both of them could be targeted by Indomethacin.

摘要

本研究旨在确定治疗强直性脊柱炎(AS)的潜在靶基因。从基因表达综合数据库下载数据集GSE25101,其中包括16份AS血样和16份正常对照血样。使用limma软件包中的非配对t检验鉴定差异表达基因(DEG),校正P<0.05。使用人类转录组多方面分析工具进行基因本体生物学过程(GO-BP)和京都基因与基因组百科全书(KEGG)富集分析。使用STRING和Cytoscape构建蛋白质-蛋白质相互作用(PPI)网络,并使用MCODE插件进行模块分析。利用Webgestal预测转录因子(TF)-微小RNA-靶标网络,并应用比较毒理基因组学数据库(CTD)预测化学-靶标网络。共鉴定出334个DEG,包括136个上调基因和198个下调基因。根据STRING构建PPI网络,筛选出1个显著聚类模块,得分=6.33。MAPK7(度=11)和NDUFS4(度=10)是PPI网络中的两个重要节点,它们均在cAMP介导的信号通路中显著富集(P=2.02E-02)。MAPK7可受NFY调控。MAPK7和NDUFS4均为吲哚美辛的潜在靶点。MAPK7和NDUFS4通过cAMP介导的信号通路在AS发病机制中起重要作用。它们均可被吲哚美辛靶向作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9817/5842021/cb11db226499/medi-97-e9760-g001.jpg

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