Farré Pau, Jones Meaghan J, Meaney Michael J, Emberly Eldon, Turecki Gustavo, Kobor Michael S
Department of Physics, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6 Canada.
Centre for Molecular Medicine and Therapeutics, Child & Family Research Institute, 950 W 28th ave, Vancouver, BC V5Z4H4 Canada ; Department of Medical Genetics, University of British Columbia, 950 W 28th ave, Vancouver, BC V5Z4H4 Canada.
Epigenetics Chromatin. 2015 May 9;8:19. doi: 10.1186/s13072-015-0011-y. eCollection 2015.
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.
DNA甲基化是一种表观遗传标记，可平衡可塑性与稳定性。虽然DNA甲基化具有组织特异性，但它也会随年龄以及潜在的环境暴露而变化。在DNA甲基化研究中，来自特定组织（尤其是大脑）的样本通常有限，因此常常使用替代组织。迄今为止，我们尚未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。
我们采用主成分分析来分析来自Illumina 450K人类甲基化芯片的数据，该分析使用了一组17名个体的3个脑区和全血样本。我们分析中排名前五的主成分均与一个感兴趣的变量相关：主成分1（PC1）区分了脑和血，主成分2和3分别代表脑和血中的组织组成，主成分4和5与个体年龄相关（脑样本中的PC4以及脑和血样本中的PC5）。我们在四个独立样本集中验证了与年龄相关的主成分，包括额外的脑和血样本以及肝和颊细胞样本。对所有五个主成分的基因本体分析表明，与每个主成分功能相关的过程显著富集。
主成分分析（PCA）允许对组织组成和其他感兴趣的表型进行同时且独立的分析。我们发现了一种与细胞类型组成无关且无需对细胞异质性进行校正的年龄表观遗传特征。
