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M3D: a kernel-based test for spatially correlated changes in methylation profiles

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    Rights statement: © The Author 2014. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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http://bioinformatics.oxfordjournals.org/content/31/6/809
Original languageEnglish
Pages (from-to)809-816
Number of pages8
JournalBioinformatics
Volume31
Issue number6
Early online date13 Nov 2014
DOIs
StatePublished - 6 Mar 2015

Abstract

MOTIVATION: 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.

AVAILABILITY AND IMPLEMENTATION: R/Bioconductor package M(3)D.

CONTACT: G.Sanguinetti@ed.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.

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