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Identification of differentially methylated cell types in epigenome-wide association studies

Zheng, S; Breeze, C; Beck, S; Teschendorff, AE; (2018) Identification of differentially methylated cell types in epigenome-wide association studies. Nature Methods , 15 1059 -1066. 10.1038/s41592-018-0213-x. Green open access

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Abstract

An outstanding challenge of epigenome-wide association studies (EWASs) performed in complex tissues is the identification of the specific cell type(s) responsible for the observed differential DNA methylation. Here we present a statistical algorithm called CellDMC (https://github.com/sjczheng/EpiDISH), which can identify differentially methylated positions and the specific cell type(s) driving the differential methylation. We validated 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. CellDMC achieved over 90% sensitivity and specificity in scenarios where current state-of-the-art methods did not identify differential methylation. By applying CellDMC to an EWAS performed in buccal swabs, we identified smoking-associated differentially methylated positions occurring in the epithelial compartment, which we validated in smoking-related lung cancer. CellDMC may be useful in the identification of causal DNA-methylation alterations in disease.

Type: Article
Title: Identification of differentially methylated cell types in epigenome-wide association studies
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41592-018-0213-x
Publisher version: https://doi.org/10.1038/s41592-018-0213-x
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/10058364
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