• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Epigenetics & Chromatin >Concordant and discordant DNA methylation signatures of aging in human blood and brain
【24h】

Concordant and discordant DNA methylation signatures of aging in human blood and brain

机译：人类血液和大脑衰老的一致和不一致DNA甲基化特征

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Background 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. Results 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. Conclusions 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.
机译：背景DNA甲基化是表观遗传标记，可平衡可塑性和稳定性。尽管DNA甲基化表现出组织特异性，但它也可能随年龄和潜在的环境暴露而变化。在DNA甲基化研究中，经常会限制来自特定组织（尤其是大脑）的样本，因此经常使用替代组织。到目前为止，我们还不完全了解这些替代组织的DNA甲基化图谱与目标中央组织的图谱之间的关系。结果我们调整了主成分分析，以使用一组具有3个大脑区域和全血的17个人来分析Illumina 450K人类甲基化阵列的数据。我们分析中前五位的主要成分均与感兴趣的变量相关：主要成分1（PC1）区分了大脑与血液，PC 2和3分别代表大脑和血液中的组织组成，PC 4和5与个体年龄有关（大脑中的PC4和大脑和血液中的PC5）。我们在四个独立的样本集中验证了与年龄相关的PC，包括另外的大脑和血液样本以及肝和颊细胞。对所有五台PC的基因本体分析表明，丰富的过程可以告知每台PC功能。结论主成分分析（PCA）允许同时独立地分析组织组成和其他感兴趣的表型。我们发现年龄的表观遗传学签名与细胞类型组成无关，并且不需要校正细胞异质性。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号