A method for identifying differentially methylated regions. First, the data is divided into smaller segments based on genomic distance between consecutive probes. Then, each of these segments is divided into regions with consistent differential methylation patterns. For this, all possible segmentations are considered and the optimal one is chosen according to the minimum description length (MDL) principle. Finally, the significance of differential methylation in each region is assessed using linear mixed models. Using both simulated and large publicly available methylation datasets, we compare seqlm performance to alternative approaches. We demonstrate that it is both more sensitive and specific than competing methods. This is achieved with minimal parameter tuning and, surprisingly, quickest running time of all the tried methods. Finally, we show that the regional differential methylation patterns identified on sparse array data are confirmed by higher resolution sequencing approaches.

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seqlm specifications

Software type:
Package
Restrictions to use:
None
Biological technology:
Illumina
Programming languages:
R
Stability:
Stable
Interface:
Command line interface
Input data:
A matrix with methylation values; a vector specifying the classes of columns (only two-class case is supported currently) or a continuous variable; location information about the methylation probes in GRanges format
Operating system:
Unix/Linux, Mac OS, Windows
Computer skills:
Advanced

Publications

  • (Kolde et al., 2016) seqlm: an MDL based method for identifying differentially methylated regions in high density methylation array data. Bioinformatics.
    DOI: 10.1093/bioinformatics/btw304

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Maintainer

Credits

Institution(s)

Institute of Computer Science, University of Tartu, Tartu, Estonia; Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA, USA; Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia

Link to literature

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