A Qualitative Analysis Based on Relative Expression Orderings Identifies Transcriptional Subgroups for Alzheimer's Disease.
A Qualitative Analysis Based on Relative Expression Orderings Identifies Transcriptional Subgroups for Alzheimer's Disease.
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DOI：
10.2174/1567205016666191122125035
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发表时间：
2019-11
影响因子：
2.1
通讯作者：
Guini Hong;Pengming Zeng;Na Li;H. Cai;You Guo;Xiaopeng Li;Keshen Li;Hongdong Li
中科院分区：
文献类型：
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作者：
Guini Hong;Pengming Zeng;Na Li;H. Cai;You Guo;Xiaopeng Li;Keshen Li;Hongdong Li
阿尔茨海默病（Alzheimer 'sdisease，AD）是一种异质性神经退行性疾病。然而，很少有研究调查的异质性基因表达模式在AD。目的与方法采用样本内相对表达排序（REO）方法，研究AD患者4个脑区的基因表达模式。与非AD对照相比，AD样品中具有显著逆转的REO的基因对使用Fisher精确检验针对每个脑区域进行鉴定，并根据它们在AD样品之间的转录差异进行过滤。采用聚类分析方法对AD亚组进行分类。结果基于REO的基因表达谱分析显示，AD患者存在转录差异以及不同的疾病亚型。对于每个脑区，分为两个主要亚组：一个亚组报告了与年龄相关基因重叠的差异表达基因，另一个亚组可能与神经炎症有关。结论AD转录亚群有助于了解AD的发病机制，为AD的个体化治疗提供依据。
BACKGROUND Alzheimer's disease (AD) is a heterogeneous neurodegenerative disease. However, few studies have investigated the heterogeneous gene expression patterns in AD. OBJECTIVE AND METHODS We examined the gene expression patterns in four brain regions of AD based on the within-sample relative expression orderings (REOs). Gene pairs with significantly reversed REOs in AD samples compared to non-AD controls were identified for each brain region using Fisher's exact test, and filtered according to their transcriptional differences between AD samples. Subgroups of AD were classified by cluster analysis. RESULTS REO-based gene expression profiling analyses revealed that transcriptional differences, as well as distinct disease subsets, existed within AD patients. For each brain region, two main subgroups were classified: one subgroup reported differentially expressed genes overlapped with the age-related genes, and the other might relate to neuroinflammation. CONCLUSION AD transcriptional subgroups might help understand the underlying pathogenesis of AD, and lend support to a personalized approach to AD management.