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bioRxiv · 10.1101/421966

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

Zheng, S. C.·Breeze, C. E.·Beck, S.·Teschendorff, A.
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Abstract

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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Zheng, S. C., Breeze, C. E., Beck, S., Teschendorff, A.. 2018-09-20. Identification of differentially methylated cell-types in Epigenome-Wide Association Studies. https://doi.org/10.1101/421966

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