EMeth: An EM algorithm for cell type decomposition based on DNA methylation data

Abstract We introduce a new computational method named EMeth to estimate cell type proportions using DNA methylation data. EMeth is a reference-based method that requires cell type-specific DNA methylation data from relevant cell types. EMeth improves on the existing reference-based methods by detec...

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Autores principales:	Hanyu Zhang, Ruoyi Cai, James Dai, Wei Sun
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ac4262b5b25c4c71920cdd02388a298b
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spelling	oai:doaj.org-article:ac4262b5b25c4c71920cdd02388a298b2021-12-02T13:19:21ZEMeth: An EM algorithm for cell type decomposition based on DNA methylation data10.1038/s41598-021-84864-92045-2322https://doaj.org/article/ac4262b5b25c4c71920cdd02388a298b2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84864-9https://doaj.org/toc/2045-2322Abstract We introduce a new computational method named EMeth to estimate cell type proportions using DNA methylation data. EMeth is a reference-based method that requires cell type-specific DNA methylation data from relevant cell types. EMeth improves on the existing reference-based methods by detecting the CpGs whose DNA methylation are inconsistent with the deconvolution model and reducing their contributions to cell type decomposition. Another novel feature of EMeth is that it allows a cell type with known proportions but unknown reference and estimates its methylation. This is motivated by the case of studying methylation in tumor cells while bulk tumor samples include tumor cells as well as other cell types such as infiltrating immune cells, and tumor cell proportion can be estimated by copy number data. We demonstrate that EMeth delivers more accurate estimates of cell type proportions than several other methods using simulated data and in silico mixtures. Applications in cancer studies show that the proportions of T regulatory cells estimated by DNA methylation have expected associations with mutation load and survival time, while the estimates from gene expression miss such associations.Hanyu ZhangRuoyi CaiJames DaiWei SunNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hanyu Zhang Ruoyi Cai James Dai Wei Sun EMeth: An EM algorithm for cell type decomposition based on DNA methylation data
description	Abstract We introduce a new computational method named EMeth to estimate cell type proportions using DNA methylation data. EMeth is a reference-based method that requires cell type-specific DNA methylation data from relevant cell types. EMeth improves on the existing reference-based methods by detecting the CpGs whose DNA methylation are inconsistent with the deconvolution model and reducing their contributions to cell type decomposition. Another novel feature of EMeth is that it allows a cell type with known proportions but unknown reference and estimates its methylation. This is motivated by the case of studying methylation in tumor cells while bulk tumor samples include tumor cells as well as other cell types such as infiltrating immune cells, and tumor cell proportion can be estimated by copy number data. We demonstrate that EMeth delivers more accurate estimates of cell type proportions than several other methods using simulated data and in silico mixtures. Applications in cancer studies show that the proportions of T regulatory cells estimated by DNA methylation have expected associations with mutation load and survival time, while the estimates from gene expression miss such associations.
format	article
author	Hanyu Zhang Ruoyi Cai James Dai Wei Sun
author_facet	Hanyu Zhang Ruoyi Cai James Dai Wei Sun
author_sort	Hanyu Zhang
title	EMeth: An EM algorithm for cell type decomposition based on DNA methylation data
title_short	EMeth: An EM algorithm for cell type decomposition based on DNA methylation data
title_full	EMeth: An EM algorithm for cell type decomposition based on DNA methylation data
title_fullStr	EMeth: An EM algorithm for cell type decomposition based on DNA methylation data
title_full_unstemmed	EMeth: An EM algorithm for cell type decomposition based on DNA methylation data
title_sort	emeth: an em algorithm for cell type decomposition based on dna methylation data
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ac4262b5b25c4c71920cdd02388a298b
work_keys_str_mv	AT hanyuzhang emethanemalgorithmforcelltypedecompositionbasedondnamethylationdata AT ruoyicai emethanemalgorithmforcelltypedecompositionbasedondnamethylationdata AT jamesdai emethanemalgorithmforcelltypedecompositionbasedondnamethylationdata AT weisun emethanemalgorithmforcelltypedecompositionbasedondnamethylationdata
_version_	1718393290378706944

EMeth: An EM algorithm for cell type decomposition based on DNA methylation data

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