HMM-DM: identifying differentially methylated regions using a hidden Markov model

Stat Appl Genet Mol Biol. 2016 Mar;15(1):69-81. doi: 10.1515/sagmb-2015-0077.


DNA methylation is an epigenetic modification involved in organism development and cellular differentiation. Identifying differential methylations can help to study genomic regions associated with diseases. Differential methylation studies on single-CG resolution have become possible with the bisulfite sequencing (BS) technology. However, there is still a lack of efficient statistical methods for identifying differentially methylated (DM) regions in BS data. We have developed a new approach named HMM-DM to detect DM regions between two biological conditions using BS data. This new approach first uses a hidden Markov model (HMM) to identify DM CG sites accounting for spatial correlation across CG sites and variation across samples, and then summarizes identified sites into regions. We demonstrate through a simulation study that our approach has a superior performance compared to BSmooth. We also illustrate the application of HMM-DM using a real breast cancer dataset.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Breast Neoplasms / genetics
  • Computer Simulation
  • DNA Methylation*
  • Epigenomics / methods*
  • Female
  • Humans
  • Markov Chains*
  • Reproducibility of Results
  • Sensitivity and Specificity