A meta-analysis of public microarray data identifies gene regulatory pathways deregulated in peripheral blood mononuclear cells from individuals with Systemic Lupus Erythematosus compared to those without.

A meta-analysis of public microarray data identifies gene regulatory pathways deregulated in peripheral blood mononuclear cells from individuals with Systemic Lupus Erythematosus compared to those without.
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DOI:
10.1186/s12920-016-0227-0
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发表时间:
2016-11-15
影响因子:
2.7
通讯作者:
Tiffin N
Tiffin N
中科院分区:
医学3区
文献类型:
--
作者:
Kröger W;Mapiye D;Entfellner JD;Tiffin N

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系统性红斑狼疮(SLE)是一种复杂的、多系统的自身免疫性疾病,其潜在的病因学机制尚不清楚。人们使用各种组学方法对狼疮的遗传和分子过程进行了广泛的研究,包括全基因组关联研究、候选基因研究以及狼疮样本与对照中差异基因表达的微阵列实验。本研究分析了现有微阵列数据集的组合,以确定与未受影响的对照相比,SLE 患者的人外周血单核细胞中失调的差异调节遗传途径。分位数离散化和缩放这两种统计方法用于组合公开可用的表达微阵列数据集并对差异表达基因进行荟萃分析。通过荟萃分析鉴定出与干扰素信号传导有关的差异表达基因,这与生成所用数据集的各个研究的结果一致。然而,与个别研究相反,荟萃分析和随后的通路分析还强调,与对照组相比,SLE 患者的外周血单核细胞 (PBMC) 中 TLR 信号传导、氧化磷酸化和血细胞渗出以及粘附调节网络受到差异性调节。我们的分析表明,可以使用荟萃分析技术从公开的表达数据中获取更多信息,这与样本数量有限的罕见疾病的研究特别相关。本文的在线版本 (doi:10.1186/s12920-016-0227-0) 包含补充材料,可供授权用户使用。
Systemic Lupus Erythematosus (SLE) is a complex, multi-systemic, autoimmune disease for which the underlying aetiological mechanisms are poorly understood. The genetic and molecular processes underlying lupus have been extensively investigated using a variety of -omics approaches, including genome-wide association studies, candidate gene studies and microarray experiments of differential gene expression in lupus samples compared to controls. This study analyses a combination of existing microarray data sets to identify differentially regulated genetic pathways that are dysregulated in human peripheral blood mononuclear cells from SLE patients compared to unaffected controls. Two statistical approaches, quantile discretisation and scaling, are used to combine publicly available expression microarray datasets and perform a meta-analysis of differentially expressed genes. Differentially expressed genes implicated in interferon signaling were identified by the meta-analysis, in agreement with the findings of the individual studies that generated the datasets used. In contrast to the individual studies, however, the meta-analysis and subsequent pathway analysis additionally highlighted TLR signaling, oxidative phosphorylation and diapedesis and adhesion regulatory networks as being differentially regulated in peripheral blood mononuclear cells (PBMCs) from SLE patients compared to controls. Our analysis demonstrates that it is possible to derive additional information from publicly available expression data using meta-analysis techniques, which is particularly relevant to research into rare diseases where sample numbers can be limiting. The online version of this article (doi:10.1186/s12920-016-0227-0) contains supplementary material, which is available to authorized users.
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