MethCP: Differentially Methylated Region Detection with Change Point Models

J Comput Biol. 2020 Apr;27(4):458-471. doi: 10.1089/cmb.2019.0326. Epub 2020 Mar 16.

Abstract

Whole-genome bisulfite sequencing (WGBS) provides a precise measure of methylation across the genome, yet presents a challenge in identifying differentially methylated regions (DMRs) between different conditions. Many methods have been developed, which focus primarily on the setting of two-group comparison. We develop a DMR detecting method MethCP for WGBS data, which is applicable for a wide range of experimental designs beyond the two-group comparisons, such as time-course data. MethCP identifies DMRs based on change point detection, which naturally segments the genome and provides region-level differential analysis. For simple two-group comparison, we show that our method outperforms developed methods in accurately detecting the complete DMR on a simulated data set and an Arabidopsis data set. Moreover, we show that MethCP is capable of detecting wide regions with small effect sizes, which can be common in some settings, but existing techniques are poor in detecting such DMRs. We also demonstrate the use of MethCP for time-course data on another data set after methylation throughout seed germination in Arabidopsis.

Keywords: bisulfite sequencing; change point detection; differential methylation.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Computational Biology / methods
  • DNA Methylation / genetics*
  • Genome / genetics*
  • Molecular Sequence Annotation
  • Sequence Analysis, DNA / methods
  • Software*
  • Whole Genome Sequencing / methods*