Reference-free deconvolution of DNA methylation data and mediation by cell composition effects.
Reference-free deconvolution of DNA methylation data and mediation by cell composition effects.
复制标题
通过细胞组成效应对DNA甲基化数据和介导的无参考反卷积。
DOI：
10.1186/s12859-016-1140-4
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发表时间：
2016-06-29
影响因子：
3
通讯作者：
Marsit CJ
中科院分区：
文献类型：
--
作者：
Houseman EA;Kile ML;Christiani DC;Ince TA;Kelsey KT;Marsit CJ
最近对DNA甲基化数据的无参考去卷积的兴趣导致了几种有监督的方法，但这些方法不容易允许解释潜在的细胞类型。我们提出了一种简单的无参考去卷积方法，它既提供了由其潜在的甲基组定义的假定细胞类型的比例，这些组成细胞类型的数量，也提供了一种评估潜在的甲基组反映特定类型的细胞的程度的方法。我们在对来自13个不同数据收集工作的23个Infinium数据集的分析中演示了这些方法；这些经验评估表明，我们的算法可以合理地估计成分类型的数量，返回显示与潜在表型数据的预期关联的细胞比例估计，以及反映组成细胞类型的潜在生物学的甲基组。我们的方法允许通过细胞组成效应来明确量化DNA甲基化与表型相关的中介作用。虽然需要更多的工作来研究与估计的甲基组相关的功能信息，但我们提出的方法为在缺乏参考数据的异种组织中进行DNA甲基化研究提供了一个新的和有用的基础。本文的在线版本(doi：10.1186/s12859-0161140-4)包含补充材料，授权用户可以使用。
Recent interest in reference-free deconvolution of DNA methylation data has led to several supervised methods, but these methods do not easily permit the interpretation of underlying cell types. We propose a simple method for reference-free deconvolution that provides both proportions of putative cell types defined by their underlying methylomes, the number of these constituent cell types, as well as a method for evaluating the extent to which the underlying methylomes reflect specific types of cells. We demonstrate these methods in an analysis of 23 Infinium data sets from 13 distinct data collection efforts; these empirical evaluations show that our algorithm can reasonably estimate the number of constituent types, return cell proportion estimates that demonstrate anticipated associations with underlying phenotypic data; and methylomes that reflect the underlying biology of constituent cell types. Our methodology permits an explicit quantitation of the mediation of phenotypic associations with DNA methylation by cell composition effects. Although more work is needed to investigate functional information related to estimated methylomes, our proposed method provides a novel and useful foundation for conducting DNA methylation studies on heterogeneous tissues lacking reference data. The online version of this article (doi:10.1186/s12859-016-1140-4) contains supplementary material, which is available to authorized users.