Estimating cell-type-specific DNA methylation effects in heterogeneous cellular populations
Estimating cell-type-specific DNA methylation effects in heterogeneous cellular populations
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DOI：
10.2217/epi-2020-0147
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发表时间：
2020-12-22
期刊：
影响因子：
3.8
通讯作者：
Liang, Liming
中科院分区：
文献类型：
--
作者：
Feng, Yen-Chen A.;Guo, Yichen;Liang, Liming
目的：开发一种在存在细胞类型异质性的情况下估计表观基因组关联研究中细胞特异性效应的方法。材料和方法：我们利用Monte Carlo期望最大化（MCEM）算法和Metropolis-Hastings采样器重建“缺失”的细胞特异性甲基化，并估计它们与表型的关联，不受细胞类型比例的干扰。结果：模拟显示了该方法在各种设置下的可靠性能，包括当细胞类型罕见时。应用于真实的数据集概括了全血中直接测量的细胞特异性甲基化模式。结论：这项工作提供了一个框架，以确定重要的细胞群和帐户的细胞类型组成有用的研究人类性状和疾病的表观遗传变化的作用。
Aim: To develop a method for estimating cell-specific effects in epigenomic association studies in the presence of cell type heterogeneity. Materials & methods: We utilized Monte Carlo Expectation-Maximization (MCEM) algorithm with Metropolis-Hastings sampler to reconstruct the 'missing' cell-specific methylations and to estimate their associations with phenotypes free of confounding by cell type proportions. Results: Simulations showed reliable performance of the method under various settings including when the cell type is rare. Application to a real dataset recapitulated the directly measured cell-specific methylation pattern in whole blood. Conclusion: This work provides a framework to identify important cell groups and account for cell type composition useful for studying the role of epigenetic changes in human traits and diseases.