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基于生物信息学分析的系统性红斑狼疮潜在蛋白生物标志物。

Potential protein biomarkers for systemic lupus erythematosus determined by bioinformatics analysis.

机构信息

Department of Rheumatology, Affiliated Hospital of Nantong University, No. 20, XiSi Road, Nantong, Jiangsu Province, 226001, PR China; Department of Rheumatology, Nantong First People's Hospital, Nantong, Jiangsu Province, 226001, PR China.

Department of Rheumatology, Affiliated Hospital of Nantong University, No. 20, XiSi Road, Nantong, Jiangsu Province, 226001, PR China.

出版信息

Comput Biol Chem. 2019 Dec;83:107135. doi: 10.1016/j.compbiolchem.2019.107135. Epub 2019 Oct 31.

Abstract

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disorder, and its pathogenesis in males and in cases without accompanying lupus nephritis (LN) is not fully understood. In this study, we identified 90 (82 up- and 8 downregulated) differentially expressed genes (DEGs) common to female LN, female LN and male LN using the GSE65391 and GSE49454 gene expression datasets from Gene Expression Omnibus database (GEO). The protein-protein interaction (PPI) network of 70 DEGs was constructed using STRING and cytoscape, and the Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the PPI network was significantly enriched in defense response to virus, cytosol, protein binding and measles. Sixteen hubgenes were identified from this PPI network, and Literature Mining Gene Networks molecular of GenCLiP 2.0 showed strong interaction between STAT1, DDX58 and IFIT1. Enrichment analysis of hubgenes in published literature showed the involvement of immune response and interferon-related genes in the pathogenesis of SLE. In addition, the transcription factors STAT1 & 2 and IRF6 & 9 had high Normalized Enrichment Score (NES). The 70 DEGs with PPI network and 16 hubgenes are potential biomarkers of SLE, and can help improve diagnosis and develop individualized therapies.

摘要

系统性红斑狼疮(SLE)是一种异质性自身免疫性疾病,其男性患者和不伴有狼疮肾炎(LN)患者的发病机制尚不完全清楚。本研究通过基因表达数据库(GEO)中的 GSE65391 和 GSE49454 基因表达数据集,鉴定出女性 LN、女性 LN 和男性 LN 共有的 90 个(82 个上调和 8 个下调)差异表达基因(DEGs)。使用 STRING 和 cytoscape 构建了 70 个 DEGs 的蛋白质-蛋白质相互作用(PPI)网络,基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析表明,PPI 网络显著富集于抗病毒防御反应、细胞质、蛋白质结合和麻疹。从该 PPI 网络中鉴定出 16 个枢纽基因,并且 GenCLiP 2.0 的 Literature Mining Gene Networks 分子显示 STAT1、DDX58 和 IFIT1 之间存在强烈的相互作用。在已发表文献中对枢纽基因的富集分析表明,免疫反应和干扰素相关基因参与了 SLE 的发病机制。此外,转录因子 STAT1 和 2 以及 IRF6 和 9 具有较高的归一化富集分数(NES)。具有 PPI 网络和 16 个枢纽基因的 70 个 DEGs 是 SLE 的潜在生物标志物,有助于改善诊断并开发个体化治疗方法。

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