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儿童哮喘中差异表达基因的鉴定

Identification of differentially expressed genes in childhood asthma.

作者信息

Zhang Nian-Zhen, Chen Xiu-Juan, Mu Yu-Hua, Wang Hewen

机构信息

Department of Pediatrics Department of Gynecology Department of General Surgery, Rizhao People's Hospital, Rizhao, China.

出版信息

Medicine (Baltimore). 2018 May;97(21):e10861. doi: 10.1097/MD.0000000000010861.

Abstract

Asthma has been the most common chronic disease in children that places a major burden for affected people and their families.An integrated analysis of microarrays studies was performed to identify differentially expressed genes (DEGs) in childhood asthma compared with normal control. We also obtained the differentially methylated genes (DMGs) in childhood asthma according to GEO. The genes that were both differentially expressed and differentially methylated were identified. Functional annotation and protein-protein interaction network construction were performed to interpret biological functions of DEGs. We performed q-RT-PCR to verify the expression of selected DEGs.One DNA methylation and 3 gene expression datasets were obtained. Four hundred forty-one DEGs and 1209 DMGs in childhood asthma were identified. Among which, 16 genes were both differentially expressed and differentially methylated in childhood asthma. Natural killer cell mediated cytotoxicity pathway, Jak-STAT signaling pathway, and Wnt signaling pathway were 3 significantly enriched pathways in childhood asthma according to our KEGG enrichment analysis. The PPI network of top 20 up- and downregulated DEGs consisted of 822 nodes and 904 edges and 2 hub proteins (UBQLN4 and MID2) were identified. The expression of 8 DEGs (GZMB, FGFBP2, CLC, TBX21, ALOX15, IL12RB2, UBQLN4) was verified by qRT-PCR and only the expression of GZMB and FGFBP2 was inconsistent with our integrated analysis.Our finding was helpful to elucidate the underlying mechanism of childhood asthma and develop new potential diagnostic biomarker and provide clues for drug design.

摘要

哮喘一直是儿童中最常见的慢性病,给患者及其家庭带来了沉重负担。我们进行了一项微阵列研究的综合分析,以鉴定儿童哮喘与正常对照相比差异表达的基因(DEG)。我们还根据基因表达综合数据库(GEO)获得了儿童哮喘中的差异甲基化基因(DMG)。鉴定出既差异表达又差异甲基化的基因。进行功能注释和蛋白质-蛋白质相互作用网络构建以解释DEG的生物学功能。我们进行了定量逆转录聚合酶链反应(q-RT-PCR)以验证所选DEG的表达。获得了一个DNA甲基化和3个基因表达数据集。鉴定出儿童哮喘中的441个DEG和1209个DMG。其中,有16个基因在儿童哮喘中既差异表达又差异甲基化。根据我们的京都基因与基因组百科全书(KEGG)富集分析,自然杀伤细胞介导的细胞毒性途径、 Jak-STAT信号通路和Wnt信号通路是儿童哮喘中3条显著富集的途径。前20个上调和下调DEG的蛋白质-蛋白质相互作用(PPI)网络由822个节点和904条边组成,并鉴定出2个枢纽蛋白(泛素样蛋白4和MID2)。通过qRT-PCR验证了8个DEG(颗粒酶B、成纤维细胞生长因子结合蛋白2、氯离子细胞内通道蛋白、T-box转录因子21、花生四烯酸15-脂氧合酶、白细胞介素12受体β2、泛素样蛋白4)的表达,只有颗粒酶B和成纤维细胞生长因子结合蛋白2的表达与我们的综合分析不一致。我们的发现有助于阐明儿童哮喘的潜在机制,开发新的潜在诊断生物标志物,并为药物设计提供线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c308/6392650/5e995fee8324/medi-97-e10861-g003.jpg

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