UMMS Affiliation

Program in Bioinformatics and Integrative Biology

Date

4-1-2014

Document Type

Article

Subjects

Cytosine; *DNA Methylation; Sequence Alignment; Sequence Analysis, DNA; *Software; Sulfites

Disciplines

Bioinformatics | Computational Biology

Abstract

Analysis of bisulfite sequencing data usually requires two tasks: to call methylated cytosines (mCs) in a sample, and to detect differentially methylated regions (DMRs) between paired samples. Although numerous tools have been proposed for mC calling, methods for DMR detection have been largely limited. Here, we present Bisulfighter, a new software package for detecting mCs and DMRs from bisulfite sequencing data. Bisulfighter combines the LAST alignment tool for mC calling, and a novel framework for DMR detection based on hidden Markov models (HMMs). Unlike previous attempts that depend on empirical parameters, Bisulfighter can use the expectation-maximization algorithm for HMMs to adjust parameters for each data set. We conduct extensive experiments in which accuracy of mC calling and DMR detection is evaluated on simulated data with various mC contexts, read qualities, sequencing depths and DMR lengths, as well as on real data from a wide range of biological processes. We demonstrate that Bisulfighter consistently achieves better accuracy than other published tools, providing greater sensitivity for mCs with fewer false positives, more precise estimates of mC levels, more exact locations of DMRs and better agreement of DMRs with gene expression and DNase I hypersensitivity. The source code is available at http://epigenome.cbrc.jp/bisulfighter.

Rights and Permissions

Citation: Nucleic Acids Res. 2014 Apr;42(6):e45. doi: 10.1093/nar/gkt1373. Epub 2014 Jan 13. Link to article on publisher's site.

DOI of Published Version

10.1093/nar/gkt1373

Comments

© The Author(s) 2014. Published by Oxford University Press.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com.

Related Resources

Link to Article in PubMed

Journal Title

Nucleic acids research

PubMed ID

24423865

Creative Commons License

Creative Commons Attribution-Noncommercial 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 3.0 License

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