Bioinformatics analyses of differentially expressed genes associated with spinal cord injury: a microarray-based analysis in a mouse model
Bioinformatics analyses of differentially expressed genes associated with spinal cord injury: a microarray-based analysis in a mouse model
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DOI：
10.4103/1673-5374.251335
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发表时间：
2019-07-01
影响因子：
6.1
通讯作者：
Liu, Ji-Jun
中科院分区：
文献类型：
--
作者：
Guo, Lei;Lv, Jing;Liu, Ji-Jun
基因谱分析表明，脊髓损伤后基因表达和信号通路发生了显著变化，这可能会影响损伤部位的微环境。基因芯片分析为研究脊髓损伤的诊断、治疗和预后提供了新的机会。然而，差异表达的基因在不同的研究中并不一致，许多关键基因和信号通路还没有得到准确的研究。GSE5296检索自基因表达总括数据集。使用R/BioConductor软件获得差异表达基因(表达变化至少两倍；P<；0.05)。注释、可视化和集成发现数据库用于差异表达基因的功能注释，动物转录因子数据库用于预测潜在的转录因子。由此产生的转录调控蛋白相互作用网络被绘制成地图，以筛选具有代表性的基因，并调查它们对疾病的诊断和治疗价值。总体而言，这项研究确定了在脊髓损伤后0.5、4和24小时以及3、7和28天上调的109个基因和下调的30个基因。在各个时间点，下调基因的数量少于上调基因的数量。注释、可视化和综合发现数据库分析发现，许多炎症相关途径在损伤脊髓中上调。此外，这些炎症相关基因的表达水平至少保持了28天。此外，在上调的差异表达基因的蛋白质-蛋白质相互作用网络中，发现了399种调控模式和77个节点。在分布程度最高的10个上调差异表达基因中，有6个基因是转录因子。在这些转录因子中，ATF3的变化最大。ATF3在脊髓损伤后30分钟内表达上调，至伤后28天仍有较高水平的表达。这些通过生物信息学工具筛选出来的关键基因可以作为诊断疾病的生物标志物，为确定治疗靶点提供参考。
Gene spectrum analysis has shown that gene expression and signaling pathways change dramatically after spinal cord injury, which may affect the microenvironment of the damaged site. Microarray analysis provides a new opportunity for investigating diagnosis, treatment, and prognosis of spinal cord injury. However, differentially expressed genes are not consistent among studies, and many key genes and signaling pathways have not yet been accurately studied. GSE5296 was retrieved from the Gene Expression Omnibus DataSet. Differentially expressed genes were obtained using R/Bioconductor software (expression changed at least two-fold; P < 0.05). Database for Annotation, Visualization and Integrated Discovery was used for functional annotation of differentially expressed genes and Animal Transcription Factor Database for predicting potential transcription factors. The resulting transcription regulatory protein interaction network was mapped to screen representative genes and investigate their diagnostic and therapeutic value for disease. In total, this study identified 109 genes that were upregulated and 30 that were downregulated at 0.5, 4, and 24 hours, and 3, 7, and 28 days after spinal cord injury. The number of downregulated genes was smaller than the number of upregulated genes at each time point. Database for Annotation, Visualization and Integrated Discovery analysis found that many inflammation-related pathways were upregulated in injured spinal cord. Additionally, expression levels of these inflammation-related genes were maintained for at least 28 days. Moreover, 399 regulation modes and 77 nodes were shown in the protein-protein interaction network of upregulated differentially expressed genes. Among the 10 upregulated differentially expressed genes with the highest degrees of distribution, six genes were transcription factors. Among these transcription factors, ATF3 showed the greatest change. ATF3 was upregulated within 30 minutes, and its expression levels remained high at 28 days after spinal cord injury. These key genes screened by bioinformatics tools can be used as biological markers to diagnose diseases and provide a reference for identifying therapeutic targets.