M 3 D: A kernel-based test for spatially correlated changes in methylation profiles

Tom R. Mayo, Gabriele Schweikert, Guido Sanguinetti (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    21 Citations (Scopus)
    129 Downloads (Pure)


    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.

    Original languageEnglish
    Pages (from-to)809-816
    Number of pages8
    Issue number6
    Early online date13 Nov 2014
    Publication statusPublished - 15 Mar 2015

    ASJC Scopus subject areas

    • Statistics and Probability
    • General Medicine
    • Biochemistry
    • Molecular Biology
    • Computer Science Applications
    • Computational Theory and Mathematics
    • Computational Mathematics


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