Concordant and discordant DNA methylation signatures of aging in human blood and brain.
Concordant and discordant DNA methylation signatures of aging in human blood and brain.
复制标题
人类血液和大脑衰老的一致性和不一致的DNA甲基化特征。
DOI：
10.1186/s13072-015-0011-y
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发表时间：
2015
影响因子：
3.9
通讯作者：
Kobor MS
中科院分区：
文献类型：
--
作者：
Farré P;Jones MJ;Meaney MJ;Emberly E;Turecki G;Kobor MS
DNA甲基化是一种表观遗传标记，平衡了可塑性和稳定性。虽然DNA甲基化表现出组织特异性，但它也可能随着年龄和潜在的环境暴露而变化。在DNA甲基化的研究中，来自特定组织，特别是脑组织的样品通常是有限的，因此经常使用替代组织。到目前为止，我们还没有完全了解这些替代组织的DNA甲基化谱与感兴趣的中心组织的谱之间的关系。我们已经采用主成分分析来分析来自Illumina 450 K人类甲基化阵列的数据，该阵列使用具有3个脑区域和全血的一组17个个体。在我们的分析中，所有前五个主成分都与一个感兴趣的变量相关：主成分1（PC 1）将大脑与血液区分开来，PC 2和3分别代表大脑和血液中的组织成分，PC 4和5与个体的年龄相关（PC 4在大脑中，PC 5在大脑和血液中）。我们在四个独立的样本集中验证了我们与年龄相关的PC，包括额外的大脑和血液样本以及肝脏和口腔细胞。所有五个PC的基因本体分析表明，丰富的过程，告知每个PC的功能。主成分分析（PCA）允许同时和独立地分析组织组成和其他感兴趣的表型。我们发现了一个与细胞类型组成无关的年龄表观遗传特征，并且不需要对细胞异质性进行校正。本文的在线版本（doi：10.1186/s13072-015-0011-y）包含补充材料，可供授权用户使用。
DNA methylation is an epigenetic mark that balances plasticity with stability. While DNA methylation exhibits tissue specificity, it can also vary with age and potentially environmental exposures. In studies of DNA methylation, samples from specific tissues, especially brain, are frequently limited and so surrogate tissues are often used. As yet, we do not fully understand how DNA methylation profiles of these surrogate tissues relate to the profiles of the central tissue of interest. We have adapted principal component analysis to analyze data from the Illumina 450K Human Methylation array using a set of 17 individuals with 3 brain regions and whole blood. All of the top five principal components in our analysis were associated with a variable of interest: principal component 1 (PC1) differentiated brain from blood, PCs 2 and 3 were representative of tissue composition within brain and blood, respectively, and PCs 4 and 5 were associated with age of the individual (PC4 in brain and PC5 in both brain and blood). We validated our age-related PCs in four independent sample sets, including additional brain and blood samples and liver and buccal cells. Gene ontology analysis of all five PCs showed enrichment for processes that inform on the functions of each PC. Principal component analysis (PCA) allows simultaneous and independent analysis of tissue composition and other phenotypes of interest. We discovered an epigenetic signature of age that is not associated with cell type composition and required no correction for cellular heterogeneity. The online version of this article (doi:10.1186/s13072-015-0011-y) contains supplementary material, which is available to authorized users.
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影响因子：
10
作者：
Jiang R;Jones MJ;Sava F;Kobor MS;Carlsten C
通讯作者：
Carlsten C
影响因子：
3.7
作者：
Boks MP;Derks EM;Weisenberger DJ;Strengman E;Janson E;Sommer IE;Kahn RS;Ophoff RA
通讯作者：
Ophoff RA
影响因子：
4.5
作者：
Christensen BC;Houseman EA;Marsit CJ;Zheng S;Wrensch MR;Wiemels JL;Nelson HH;Karagas MR;Padbury JF;Bueno R;Sugarbaker DJ;Yeh RF;Wiencke JK;Kelsey KT
通讯作者：
Kelsey KT
影响因子：
12.3
作者：
Jaffe AE;Irizarry RA
通讯作者：
Irizarry RA
全基因组甲基化谱揭示了人类衰老速度的定量观点。
影响因子：
16
作者：
Hannum, Gregory;Guinney, Justin;Zhao, Ling;Zhang, Li;Hughes, Guy;Sadda, SriniVas;Klotzle, Brandy;Bibikova, Marina;Fan, Jian-Bing;Gao, Yuan;Deconde, Rob;Chen, Menzies;Rajapakse, Indika;Friend, Stephen;Ideker, Trey;Zhang, Kang
通讯作者：
Zhang, Kang