Estimating cell-type-specific DNA methylation effects in heterogeneous cellular populations

被引：2

作者：

Feng, Yen-Chen A. ^{[1
,2
,3
]}

Guo, Yichen ^{[4
,5
]}

Pain, Lucile ^{[6
]}

Lathrop, G. Mark ^{[7
,8
]}

Laprise, Catherine ^{[9
,10
]}

Moffatt, Miriam F. ^{[11
]}

Cookson, William O. C. M. ^{[11
]}

Liang, Liming ^{[1
,4
]}

机构：

[1] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[2] Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA

[3] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA

[4] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[5] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA

[6] Univ Quebec Chicoutimi, Basic Sci Dept, Quebec City, PQ G7H 2B1, Canada

[7] McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada

[8] Genome Quebec Innovat Ctr, Montreal, PQ H3A 1B1, Canada

[9] Univ Quebec Chicoutimi, Ctr Rech Sante Durable CIHR, Chicoutimi, PQ G7H 2B1, Canada

[10] Ctr Integre Univ Sante & Serv Sociaux Saguenay La, Quebec City, PQ G7H 7K9, Canada

[11] Imperial Coll, Natl Heart & Lung Inst, London SW3 6LY, England

来源：

EPIGENOMICS | 2021年 / 13卷 / 02期

关键词：

cell-type-specific effect; deconvolution; DNA methylation; epigenome-wide association study; EPIGENOME-WIDE ASSOCIATION;

D O I：

10.2217/epi-2020-0147

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：87 / 97

页数：11

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