Key Modules and Hub Genes Identified by Coexpression Network Analysis for Revealing Novel Biomarkers for Spina Bifida.

Key Modules and Hub Genes Identified by Coexpression Network Analysis for Revealing Novel Biomarkers for Spina Bifida.
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通过共表达网络分析鉴定关键模块和中心基因,揭示脊柱裂的新型生物标志物

DOI:
10.3389/fgene.2020.583316
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发表时间:
2020
影响因子:
3.7
通讯作者:
Yuan Z
Yuan Z
中科院分区:
生物学3区
文献类型:
--
作者:
Li Z;Feng J;Yuan Z

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脊柱裂是一种常见的神经管缺陷(NTD),占围产期死亡率的5-10%。脊柱裂是一种多基因遗传病,是由遗传和环境因素共同作用引起的,其确切的分子发病机制至今仍不清楚。本研究旨在通过加权基因共表达网络分析(WGCNA),寻找可能在脊柱裂发生发展中起重要作用的相关基因模块。从Gene Expression Omnibus数据库下载根据来自脊柱裂患者和健康对照的人巨噬细胞阵列的转录谱。首先,通过主成分分析(PCA)和样本聚类来识别和去除离群值。然后,确定GSE 4182数据集中前25%方差的基因,以便使用WGCNA探索潜在枢纽模块中的候选基因。经数据预处理后,共获得5407个基因,可用于进一步的WGCNA。高度相关的基因被分为19个模块。结合共表达网络和显著差异表达基因,筛选出967个可能参与脊柱裂病理过程的候选基因。结合我们之前的microRNA(miRNA)芯片结果,我们构建了一个包含4个miRNA和39个mRNA的miRNA-mRNA网络,其中3个关键基因分别与2个miRNA相关基因网络相连。经qRT-PCR验证,KCND 3在脊柱裂中表达上调。KCND 3及其相关的miR-765和miR-142- 3 p值得进一步研究。这些发现可能有助于脊柱裂的早期发现和干预,对孕妇和临床工作人员具有重要意义。
Spina bifida is a common neural tube defect (NTD) accounting for 5–10% of perinatal mortalities. As a polygenic disease, spina bifida is caused by a combination of genetic and environmental factors, for which the precise molecular pathogenesis is still not systemically understood. In the present study, we aimed to identify the related gene module that might play a vital role in the occurrence and development of spina bifida by using weighted gene co-expression network analysis (WGCNA). Transcription profiling according to an array of human amniocytes from patients with spina bifida and healthy controls was downloaded from the Gene Expression Omnibus database. First, outliers were identified and removed by principal component analysis (PCA) and sample clustering. Then, genes in the top 25% of variance in the GSE4182 dataset were then determined in order to explore candidate genes in potential hub modules using WGCNA. After data preprocessing, 5407 genes were obtained for further WGCNA. Highly correlated genes were divided into nineteen modules. Combined with a co-expression network and significant differentially expressed genes, 967 candidate genes were identified that may be involved in the pathological processes of spina bifida. Combined with our previous microRNA (miRNA) microarray results, we constructed an miRNA–mRNA network including four miRNAs and 39 mRNA among which three key genes were, respectively, linked to two miRNA-associated gene networks. Following the verification of qRT-PCR and KCND3 was upregulated in the spina bifida. KCND3 and its related miR-765 and miR-142-3p are worthy of further study. These findings may be conducive for early detection and intervention in spina bifida, as well as be of great significance to pregnant women and clinical staff.
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