Journal
BIOINFORMATICS
Volume 33, Issue 23, Pages 3701-3708Publisher
OXFORD UNIV PRESS
DOI: 10.1093/bioinformatics/btx467
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Funding
- Research Grants Council of the Hong Kong SAR, China [CUHK400913, CUHK14203915, T12-710/16-R]
- Chinese University of Hong Kong [CUHK4053135, CUHK3132753]
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Motivation: DNA methylation is an important epigenetic mechanism in gene regulation and the detection of differentially methylated regions (DMRs) is enthralling for many disease studies. There are several aspects that we can improve over existing DMR detection methods: (i) methylation statuses of nearby CpG sites are highly correlated, but this fact has seldom been modelled rigorously due to the uneven spacing; (ii) it is practically important to be able to handle both paired and unpaired samples; and (iii) the capability to detect DMRs from a single pair of samples is demanded. Results: We present DMRMark (DMR detection based on non-homogeneous hidden Markov model), a novel Bayesian framework for detecting DMRs from methylation array data. It combines the constrained Gaussian mixture model that incorporates the biological knowledge with the non-homogeneous hidden Markov model that models spatial correlation. Unlike existing methods, our DMR detection is achieved without predefined boundaries or decision windows. Furthermore, our method can detect DMRs from a single pair of samples and can also incorporate unpaired samples. Both simulation studies and real datasets from The Cancer Genome Atlas showed the significant improvement of DMRMark over other methods.
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