EPISCORE: cell type deconvolution of bulk tissue DNA methylomes from single-cell RNA-Seq data

Abstract Cell type heterogeneity presents a challenge to the interpretation of epigenome data, compounded by the difficulty in generating reliable single-cell DNA methylomes for large numbers of cells and samples. We present EPISCORE, a computational algorithm that performs virtual microdissection o...

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Main Authors: Andrew E. Teschendorff, Tianyu Zhu, Charles E. Breeze, Stephan Beck
Format: Article
Language:English
Published: BMC 2020-09-01
Series:Genome Biology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13059-020-02126-9
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author Andrew E. Teschendorff
Tianyu Zhu
Charles E. Breeze
Stephan Beck
author_facet Andrew E. Teschendorff
Tianyu Zhu
Charles E. Breeze
Stephan Beck
author_sort Andrew E. Teschendorff
collection DOAJ
description Abstract Cell type heterogeneity presents a challenge to the interpretation of epigenome data, compounded by the difficulty in generating reliable single-cell DNA methylomes for large numbers of cells and samples. We present EPISCORE, a computational algorithm that performs virtual microdissection of bulk tissue DNA methylation data at single cell-type resolution for any solid tissue. EPISCORE applies a probabilistic epigenetic model of gene regulation to a single-cell RNA-seq tissue atlas to generate a tissue-specific DNA methylation reference matrix, allowing quantification of cell-type proportions and cell-type-specific differential methylation signals in bulk tissue data. We validate EPISCORE in multiple epigenome studies and tissue types.
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spelling doaj.art-76ab0e631ac94341bf74cbd9db2892432022-12-21T19:04:28ZengBMCGenome Biology1474-760X2020-09-0121113310.1186/s13059-020-02126-9EPISCORE: cell type deconvolution of bulk tissue DNA methylomes from single-cell RNA-Seq dataAndrew E. Teschendorff0Tianyu Zhu1Charles E. Breeze2Stephan Beck3CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of SciencesCAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of SciencesAltius Institute for Biomedical SciencesUCL Cancer Institute, Paul O’Gorman Building, University College LondonAbstract Cell type heterogeneity presents a challenge to the interpretation of epigenome data, compounded by the difficulty in generating reliable single-cell DNA methylomes for large numbers of cells and samples. We present EPISCORE, a computational algorithm that performs virtual microdissection of bulk tissue DNA methylation data at single cell-type resolution for any solid tissue. EPISCORE applies a probabilistic epigenetic model of gene regulation to a single-cell RNA-seq tissue atlas to generate a tissue-specific DNA methylation reference matrix, allowing quantification of cell-type proportions and cell-type-specific differential methylation signals in bulk tissue data. We validate EPISCORE in multiple epigenome studies and tissue types.http://link.springer.com/article/10.1186/s13059-020-02126-9DNA methylationEWASSingle-cell RNA-Seq
spellingShingle Andrew E. Teschendorff
Tianyu Zhu
Charles E. Breeze
Stephan Beck
EPISCORE: cell type deconvolution of bulk tissue DNA methylomes from single-cell RNA-Seq data
Genome Biology
DNA methylation
EWAS
Single-cell RNA-Seq
title EPISCORE: cell type deconvolution of bulk tissue DNA methylomes from single-cell RNA-Seq data
title_full EPISCORE: cell type deconvolution of bulk tissue DNA methylomes from single-cell RNA-Seq data
title_fullStr EPISCORE: cell type deconvolution of bulk tissue DNA methylomes from single-cell RNA-Seq data
title_full_unstemmed EPISCORE: cell type deconvolution of bulk tissue DNA methylomes from single-cell RNA-Seq data
title_short EPISCORE: cell type deconvolution of bulk tissue DNA methylomes from single-cell RNA-Seq data
title_sort episcore cell type deconvolution of bulk tissue dna methylomes from single cell rna seq data
topic DNA methylation
EWAS
Single-cell RNA-Seq
url http://link.springer.com/article/10.1186/s13059-020-02126-9
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