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Identification of differentially methylated cell-types in Epigenome-Wide Association Studies

An outstanding challenge of Epigenome-Wide Association Studies (EWAS) performed in complex tissues is the identification of the specific cell-type(s) responsible for the observed differential DNA methylation. Here, we present a novel statistical algorithm, called CellDMC, which is able to identify n...

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Detalles Bibliográficos
Autores principales: Zheng, Shijie C, Breeze, Charles E., Beck, Stephan, Teschendorff, Andrew E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277016/
https://www.ncbi.nlm.nih.gov/pubmed/30504870
http://dx.doi.org/10.1038/s41592-018-0213-x
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author Zheng, Shijie C
Breeze, Charles E.
Beck, Stephan
Teschendorff, Andrew E.
author_facet Zheng, Shijie C
Breeze, Charles E.
Beck, Stephan
Teschendorff, Andrew E.
author_sort Zheng, Shijie C
collection PubMed
description An outstanding challenge of Epigenome-Wide Association Studies (EWAS) performed in complex tissues is the identification of the specific cell-type(s) responsible for the observed differential DNA methylation. Here, we present a novel statistical algorithm, called CellDMC, which is able to identify not only differentially methylated positions, but also the specific cell-type(s) driving the differential methylation. We provide extensive validation of CellDMC on in-silico mixtures of DNA methylation data generated with different technologies, as well as on real mixtures from epigenome-wide-association and cancer epigenome studies. We demonstrate how CellDMC can achieve over 90% sensitivity and specificity in scenarios where current state-of-the-art methods fail to identify differential methylation. By applying CellDMC to a smoking EWAS performed in buccal swabs, we identify differentially methylated positions occurring in the epithelial compartment, which we validate in smoking-related lung cancer. CellDMC may help towards the identification of causal DNA methylation alterations in disease.
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spelling pubmed-62770162019-05-30 Identification of differentially methylated cell-types in Epigenome-Wide Association Studies Zheng, Shijie C Breeze, Charles E. Beck, Stephan Teschendorff, Andrew E. Nat Methods Article An outstanding challenge of Epigenome-Wide Association Studies (EWAS) performed in complex tissues is the identification of the specific cell-type(s) responsible for the observed differential DNA methylation. Here, we present a novel statistical algorithm, called CellDMC, which is able to identify not only differentially methylated positions, but also the specific cell-type(s) driving the differential methylation. We provide extensive validation of CellDMC on in-silico mixtures of DNA methylation data generated with different technologies, as well as on real mixtures from epigenome-wide-association and cancer epigenome studies. We demonstrate how CellDMC can achieve over 90% sensitivity and specificity in scenarios where current state-of-the-art methods fail to identify differential methylation. By applying CellDMC to a smoking EWAS performed in buccal swabs, we identify differentially methylated positions occurring in the epithelial compartment, which we validate in smoking-related lung cancer. CellDMC may help towards the identification of causal DNA methylation alterations in disease. 2018-11-30 2018-12 /pmc/articles/PMC6277016/ /pubmed/30504870 http://dx.doi.org/10.1038/s41592-018-0213-x Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Zheng, Shijie C
Breeze, Charles E.
Beck, Stephan
Teschendorff, Andrew E.
Identification of differentially methylated cell-types in Epigenome-Wide Association Studies
title Identification of differentially methylated cell-types in Epigenome-Wide Association Studies
title_full Identification of differentially methylated cell-types in Epigenome-Wide Association Studies
title_fullStr Identification of differentially methylated cell-types in Epigenome-Wide Association Studies
title_full_unstemmed Identification of differentially methylated cell-types in Epigenome-Wide Association Studies
title_short Identification of differentially methylated cell-types in Epigenome-Wide Association Studies
title_sort identification of differentially methylated cell-types in epigenome-wide association studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277016/
https://www.ncbi.nlm.nih.gov/pubmed/30504870
http://dx.doi.org/10.1038/s41592-018-0213-x
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