Investigating Different DNA Methylation Patterns at the Resolution of Methylation Haplotypes

Xiaoqing Peng; Yiming Li; Xiangyan Kong; Xiaoshu Zhu; Xiaojun Ding

doi:10.3389/fgene.2021.697279

Investigating Different DNA Methylation Patterns at the Resolution of Methylation Haplotypes

Front Genet. 2021 Jun 28:12:697279. doi: 10.3389/fgene.2021.697279. eCollection 2021.

Authors

Xiaoqing Peng¹, Yiming Li¹, Xiangyan Kong², Xiaoshu Zhu³, Xiaojun Ding³

Affiliations

¹ Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
² School of Computer Science and Engineering, Central South University, Changsha, China.
³ School of Computer Science and Engineering, Yulin Normal University, Yulin, China.

Abstract

Different DNA methylation patterns presented on different tissues or cell types are considered as one of the main reasons accounting for the tissue-specific gene expressions. In recent years, many methods have been proposed to identify differentially methylated regions (DMRs) based on the mixture of methylation signals from homologous chromosomes. To investigate the possible influence of homologous chromosomes on methylation analysis, this paper proposed a method (MHap) to construct methylation haplotypes for homologous chromosomes in CpG dense regions. Through comparing the methylation consistency between homologous chromosomes in different cell types, it can be found that majority of paired methylation haplotypes derived from homologous chromosomes are consistent, while a lower methylation consistency was observed in the breast cancer sample. It also can be observed that the hypomethylation consistency of differentiated cells is higher than that of the corresponding undifferentiated stem cells. Furthermore, based on the methylation haplotypes constructed on homologous chromosomes, a method (MHap_DMR) is developed to identify DMRs between differentiated cells and the corresponding undifferentiated stem cells, or between the breast cancer sample and the normal breast sample. Through comparing the methylation haplotype modes of DMRs in two cell types, the DNA methylation changing directions of homologous chromosomes in cell differentiation and cancerization can be revealed. The code is available at: https://github.com/xqpeng/MHap_DMR.

Keywords: cell differentiation; differentially methylated region; homologous chromosomes; hypomethylation consistency; methylation consistency; methylation haplotype.