M3D: a kernel-based test for spatially correlated changes in methylation profiles.
BACKGROUND
DNA methylation is an intensely studied epigenetic mark implicated in many biological processes of direct clinical relevance. Although sequencing-based technologies are increasingly allowing high-resolution measurements of DNA methylation, statistical modelling of such data is still challenging. In particular, statistical identification of differentially methylated regions across different conditions poses unresolved challenges in accounting for spatial correlations within the statistical testing procedure.


RESULTS
We propose a non-parametric, kernel-based method, M(3)D, to detect higher order changes in methylation profiles, such as shape, across pre-defined regions. The test statistic explicitly accounts for differences in coverage levels between samples, thus handling in a principled way a major confounder in the analysis of methylation data. Empirical tests on real and simulated datasets show an increased power compared to established methods, as well as considerable robustness with respect to coverage and replication levels.
IANC, School of Informatics, University of Edinburgh, Edinburgh EH8 9AB and Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, UK.
Tom R
TR
Mayo
IANC, School of Informatics, University of Edinburgh, Edinburgh EH8 9AB and Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, UK IANC, School of Informatics, University of Edinburgh, Edinburgh EH8 9AB and Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, UK.
Gabriele
G
Schweikert
IANC, School of Informatics, University of Edinburgh, Edinburgh EH8 9AB and Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, UK.
Guido
G
Sanguinetti
D000818:Animals; D003198:Computer Simulation; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000378:metabolism*; D057890:Epigenomics; D006801:Humans; D051379:Mice; D015233:Models, Statistical; D012984:Software