Evidence map›Paper›PMID 27187204›Full record

ArticleBioinformatics (Oxford, England)2016

seqlm: an MDL based method for identifying differentially methylated regions in high density methylation array data.

Raivo Kolde, Kaspar Märtens, Kaie Lokk, Sven Laur, Jaak Vilo

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Article in Bioinformatics (Oxford, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

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25citing papers in PubMed
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25 citing papers in PubMed.

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5 · Who and what money

Authors and funding

5 authors.

Raivo KoldeInstitute of Computer Science, University of Tartu, 50409 Tartu, Estonia Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Kaspar MärtensInstitute of Computer Science, University of Tartu, 50409 Tartu, Estonia.
Kaie LokkInstitute of Molecular and Cell Biology, University of Tartu, 51010 Tartu, Estonia.
Sven LaurInstitute of Computer Science, University of Tartu, 50409 Tartu, Estonia.
Jaak ViloInstitute of Computer Science, University of Tartu, 50409 Tartu, Estonia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

motivationOne of the main goals of large scale methylation studies is to detect differentially methylated loci. One way is to approach this problem sitewise, i.e. to find differentially methylated positions (DMPs). However, it has been shown that methylation is regulated in longer genomic regions. So it is more desirable to identify differentially methylated regions (DMRs) instead of DMPs. The new high coverage arrays, like Illuminas 450k platform, make it possible at a reasonable cost. Few tools exist for DMR identification from this type of data, but there is no standard approach.

resultsWe propose a novel method for DMR identification that detects the region boundaries according to the minimum description length (MDL) principle, essentially solving the problem of model selection. The significance of the regions is established 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. AVAILABILITY AND IMPLEMENTATION: The methods have been implemented in R package seqlm that is available through Github: https://github.com/raivokolde/seqlm CONTACT: rkolde@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Indexed as

DNA MethylationDatasets as TopicGenomeGenomicsHigh-Throughput Nucleotide Sequencing

Identifiers

PMID27187204
PMCPMC5013909

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.