Development of a Method for Identifying and Functionally Analyzing Allele-Specific DNA Methylation Based on BS-Seq Data

Abstract

Aim: To comprehensively identify allele-specific DNA methylation (ASM) at the genome-wide level. Methods: Here, we propose a new method, called GeneASM, to identify ASM using high-throughput bisulfite sequencing data in the absence of haplotype information. Results: A total of 2194 allele-specific DNA methylated genes were identified in the GM12878 lymphocyte lineage using GeneASM. These genes are mainly enriched in cell cytoplasm function, subcellular component movement or cellular linkages. GM12878 methylated DNA immunoprecipitation sequencing, and methylation sensitive restriction enzyme sequencing data were used to evaluate ASM. The relationship between ASM and disease was further analyzed using the The Cancer Genome Atlas (TCGA) data of lung adenocarcinoma (LUAD), and whole genome bisulfite sequencing data. Conclusion: GeneASM, which recognizes ASM by high-throughput bisulfite sequencing and heterozygous single-nucleotide polymorphisms, provides new perspective for studying genomic imprinting.

Keywords::

• allele-specific DNA methylation
• genomic imprinting
• high-throughput sequencing
• single-nucleotide polymorphism

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2019-0023

Author contributors

Y Zhang and H Lu conceived and designed the experiments. J Zhu, Y Gu and S Zhang collected the data. S Zhang, J Zhu and Y Gu performed the analysis. Z Sun, X Zhang and W Lv participated in the discussion of the algorithm. M Su and J Zhu prepared and edited the manuscript. All authors have read and approved the final manuscript.

Financial & competing interests disclosure

This work was supported by National Natural Science Foundation of China [grant number 81573021], Project of Heilongjiang Province Department of Education [grant number 12541525]. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

The authors thank R Porter from Liwen Bianji, Edanz Editing China (www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript.

Additional information

Funding

This work was supported by National Natural Science Foundation of China [grant number 81573021], Project of Heilongjiang Province Department of Education [grant number 12541525]. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. The authors thank R Porter from Liwen Bianji, Edanz Editing China (www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript.