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A Bayesian Framework to Identify Methylcytosines from High-Throughput Bisulfite Sequencing Data

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  • Qing Xie
  • Qi Liu
  • Fengbiao Mao
  • Wanshi Cai
  • Honghu Wu
  • Mingcong You
  • Zhen Wang
  • Bingyu Chen
  • Zhong Sheng Sun
  • Jinyu Wu

Abstract

High-throughput bisulfite sequencing technologies have provided a comprehensive and well-fitted way to investigate DNA methylation at single-base resolution. However, there are substantial bioinformatic challenges to distinguish precisely methylcytosines from unconverted cytosines based on bisulfite sequencing data. The challenges arise, at least in part, from cell heterozygosis caused by multicellular sequencing and the still limited number of statistical methods that are available for methylcytosine calling based on bisulfite sequencing data. Here, we present an algorithm, termed Bycom, a new Bayesian model that can perform methylcytosine calling with high accuracy. Bycom considers cell heterozygosis along with sequencing errors and bisulfite conversion efficiency to improve calling accuracy. Bycom performance was compared with the performance of Lister, the method most widely used to identify methylcytosines from bisulfite sequencing data. The results showed that the performance of Bycom was better than that of Lister for data with high methylation levels. Bycom also showed higher sensitivity and specificity for low methylation level samples (

Suggested Citation

  • Qing Xie & Qi Liu & Fengbiao Mao & Wanshi Cai & Honghu Wu & Mingcong You & Zhen Wang & Bingyu Chen & Zhong Sheng Sun & Jinyu Wu, 2014. "A Bayesian Framework to Identify Methylcytosines from High-Throughput Bisulfite Sequencing Data," PLOS Computational Biology, Public Library of Science, vol. 10(9), pages 1-8, September.
    • Handle: RePEc:plo:pcbi00:1003853
    DOI: 10.1371/journal.pcbi.1003853
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    References listed on IDEAS

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    1. Andrew P. Feinberg, 2007. "Phenotypic plasticity and the epigenetics of human disease," Nature, Nature, vol. 447(7143), pages 433-440, May.
    2. Ryan Lister & Mattia Pelizzola & Robert H. Dowen & R. David Hawkins & Gary Hon & Julian Tonti-Filippini & Joseph R. Nery & Leonard Lee & Zhen Ye & Que-Minh Ngo & Lee Edsall & Jessica Antosiewicz-Bourg, 2009. "Human DNA methylomes at base resolution show widespread epigenomic differences," Nature, Nature, vol. 462(7271), pages 315-322, November.
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