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Meta-analysis of microarray data using a pathway-based approach identifies a 37-gene expression signature for systemic lupus erythematosus in human peripheral blood mononuclear cells

机译:使用基于途径的方法的微阵列数据的Meta分析鉴定了人体外周血单核细胞中系统性狼疮红斑的37-基因表达签名

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Background A number of publications have reported the use of microarray technology to identify gene expression signatures to infer mechanisms and pathways associated with systemic lupus erythematosus (SLE) in human peripheral blood mononuclear cells. However, meta-analysis approaches with microarray data have not been well-explored in SLE. Methods In this study, a pathway-based meta-analysis was applied to four independent gene expression oligonucleotide microarray data sets to identify gene expression signatures for SLE, and these data sets were confirmed by a fifth independent data set. Results Differentially expressed genes (DEGs) were identified in each data set by comparing expression microarray data from control samples and SLE samples. Using Ingenuity Pathway Analysis software, pathways associated with the DEGs were identified in each of the four data sets. Using the leave one data set out pathway-based meta-analysis approach, a 37-gene metasignature was identified. This SLE metasignature clearly distinguished SLE patients from controls as observed by unsupervised learning methods. The final confirmation of the metasignature was achieved by applying the metasignature to a fifth independent data set. Conclusions The novel pathway-based meta-analysis approach proved to be a useful technique for grouping disparate microarray data sets. This technique allowed for validated conclusions to be drawn across four different data sets and confirmed by an independent fifth data set. The metasignature and pathways identified by using this approach may serve as a source for identifying therapeutic targets for SLE and may possibly be used for diagnostic and monitoring purposes. Moreover, the meta-analysis approach provides a simple, intuitive solution for combining disparate microarray data sets to identify a strong metasignature. Please see Research Highlight: http://genomemedicine.com/content/3/5/30
机译:背景技术据报道,许多出版物据报道使用微阵列技术鉴定基因表达签名,以推断与人外周血单核细胞中的系统性红斑狼疮(SLE)相关的机制和途径。然而,具有微阵列数据的元分析方法并未在SLE中探索。方法在本研究中,将基于途径的META分析应用于四个独立的基因表达寡核苷酸微阵列数据集,以鉴定SLE的基因表达签名,并且通过第五独立数据集确认这些数据集。结果通过将表达微阵列数据与对照样品和SLE样品进行比较,在每个数据中鉴定出差异表达基因(DEGS)。使用Ingenuity途径分析软件,在四个数据集中的每一个中识别与DEG相关联的途径。使用留给一个数据设定的基于途径的沟率的Meta分析方法,确定了一种37基因的转移。这种SLE偏心功能清晰地区分了由无监督学习方法观察到的对照的SLE患者。通过将转移到第五个独立数据集应用,实现了转移性的最终确认。结论基于新的基于途径的META分析方法被证明是用于分组不同的微阵列数据集的有用技术。这种技术允许验证的结论跨越四个不同的数据集绘制,并由独立的第五数据集确认。通过使用该方法鉴定的转位性和途径可以用作识别SLE的治疗靶标的源,并且可能用于诊断和监测目的。此外,元分析方法提供了一种简单,直观的解决方案,用于组合不同的微阵列数据集以识别强的转位。请参阅研究亮点:http://genomemedicine.com/content/3/5/30

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