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采用生物信息学方法鉴定类风湿性关节炎相关关键基因。

Identification of key genes associated with rheumatoid arthritis with bioinformatics approach.

作者信息

Gang Xiaokun, Sun Yan, Li Fei, Yu Tong, Jiang Zhende, Zhu Xiujie, Jiang Qiyao, Wang Yao

机构信息

Department of Orthopedics, The Second Hospital of Jilin University Department of Endocrinology and Metabolism, The First Hospital of Jilin University Department of Hematology and oncology, The Second Hospital of Jilin University, Changchun, Jilin Province 130041, China.

出版信息

Medicine (Baltimore). 2017 Aug;96(31):e7673. doi: 10.1097/MD.0000000000007673.

Abstract

We aimed to identify key genes associated with rheumatoid arthritis (RA).The microarray datasets of GSE1919, GSE12021, and GSE21959 (35 RA samples and 32 normal controls) were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) in RA samples were identified using the t test in limma package. Functional enrichment analysis was performed using clusterProfiler package. A protein-protein interaction (PPI) network of selected DEGs was constructed based on the Human Protein Reference Database. Active modules were explored using the jActiveModules plug-in in the Cytoscape Network Modeling package.In total, 537 DEGs in RA samples were identified, including 241 upregulated and 296 downregulated genes. A total of 24,451 PPI pairs were collected, and 5 active modules were screened. Furthermore, 19 submodules were acquired from the 5 active modules. Discs large homolog 1 (DLG1) and related DEGs such as guanylate cyclase 1, soluble, alpha 2 (GUCY1A2), N-methyl d-aspartate receptor 2A subunit (GRIN2A), and potassium voltage-gated channel member 1 (KCNA1) were identified in 8 submodules. Plasminogen (PLG) and related DEGs such as chemokine (C-X-C motif) ligand 2 (CXCL2), laminin, alpha 3 (LAMA3), complement component 7 (C7), and coagulation factor X (F10) were identified in 4 submodules.Our results indicate that DLG1, GUCY1A2, GRIN2A, KCNA1, PLG, CXCL2, LAMA3, C7, and F10 may play key roles in the progression of RA and may serve as putative therapeutic targets for treating RA.

摘要

我们旨在鉴定与类风湿关节炎(RA)相关的关键基因。从基因表达综合数据库下载了GSE1919、GSE12021和GSE21959的微阵列数据集(35个RA样本和32个正常对照)。使用limma软件包中的t检验鉴定RA样本中的差异表达基因(DEG)。使用clusterProfiler软件包进行功能富集分析。基于人类蛋白质参考数据库构建所选DEG的蛋白质-蛋白质相互作用(PPI)网络。使用Cytoscape网络建模软件包中的jActiveModules插件探索活性模块。

总共鉴定出RA样本中的537个DEG,包括241个上调基因和296个下调基因。共收集到24451对PPI,并筛选出5个活性模块。此外,从这5个活性模块中获得了19个子模块。在8个子模块中鉴定出盘大同源物1(DLG1)以及相关的DEG,如可溶性鸟苷酸环化酶1α2(GUCY1A2)、N-甲基-D-天冬氨酸受体2A亚基(GRIN2A)和钾电压门控通道成员1(KCNA1)。在4个子模块中鉴定出纤溶酶原(PLG)以及相关的DEG,如趋化因子(C-X-C基序)配体2(CXCL2)、层粘连蛋白α3(LAMA3)、补体成分7(C7)和凝血因子X(F10)。

我们的结果表明,DLG1、GUCY1A2、GRIN2A、KCNA1、PLG、CXCL2、LAMA3、C7和F10可能在RA的进展中起关键作用,并可能作为治疗RA的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c14b/5626145/2d156cacb902/medi-96-e7673-g003.jpg

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