4.6 Article

Investigating Different DNA Methylation Patterns at the Resolution of Methylation Haplotypes

Journal

FRONTIERS IN GENETICS
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fgene.2021.697279

Keywords

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

Funding

  1. National Natural Science Foundation of China [61702555, 61662028, U1909208]
  2. National Key R&D Program of China [2018YFC0910504]
  3. 111 Project [B18059]
  4. Hunan Provincial Science and Technology Program [2018WK4001]

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This study investigates the methylation consistency between homologous chromosomes in different cell types and proposes a method to construct methylation haplotypes for homologous chromosomes. Differentiated cells show higher hypomethylation consistency compared to undifferentiated stem cells, while breast cancer samples exhibit lower methylation consistency. Additionally, a method is developed to identify DMRs between different cell types or disease states based on the methylation haplotypes, revealing DNA methylation changing directions in cell differentiation and cancerization.
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: .

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