Journal article
Genome-wide CpG density and DNA methylation analysis method (MeDIP, RRBS, and WGBS) comparisons
Epigenetics, Vol.17(5), pp.518-530
05/04/2022
PMCID: PMC9067529
PMID: 33975521
Abstract
Genome-wide DNA methylation analysis is one of the most common epigenetic processes analysed for genome characterization and differential DNA methylation assessment. Previous genome-wide analysis has suggested an important variable in DNA methylation methods involves CpG density. The current study was designed to investigate the CpG density in a variety of different species genomes and correlate this to various DNA methylation analysis data sets. The majority of all genomes had >90% of the genome in the low density 1-3 CpG/100 bp category, while <10% of the genome was in the higher density >5 CpG/100 bp category. Similar observations with human, rat, bird, and fish genomes were observed. The methylated DNA immunoprecipitation (MeDIP) procedure uses the anti-5-methylcytosine antibody immunoprecipitation followed by next-generation sequencing (MeDIP-Seq). The MeDIP procedure is biased to lower CpG density of <5 CpG/100 bp, which corresponds to >95% of the genome. The reduced representation bisulphite (RRBS) protocol generally identifies DMRs in higher CpG density regions of ≥3 CpG/100 bp which corresponds to approximately 20% of the genome. The whole-genome bisulphite (WGBS) analyses resulted in higher CpG densities, often greater than 10 CpG/100bp. WGBS generally identifies ≥2 CpG/100bp, which corresponds to approximately 50% of the genome. Limitations and potential optimization approaches for each method are discussed. None of the procedures can provide complete genome-wide assessment of the genome, but MeDIP-Seq provides coverage of the highest percentage. Observations demonstrate that CpG density is a critical variable in DNA methylation analysis, and different molecular techniques focus on distinct genomic regions.
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Details
- Title
- Genome-wide CpG density and DNA methylation analysis method (MeDIP, RRBS, and WGBS) comparisons
- Creators
- Daniel Beck - Washington State UniversityMillissia Ben Maamar - Washington State UniversityMichael K. Skinner - Washington State University
- Publication Details
- Epigenetics, Vol.17(5), pp.518-530
- Academic Unit
- Biological Sciences, School of
- Publisher
- Taylor & Francis
- Identifiers
- 99901080307501842
- Language
- English
- Resource Type
- Journal article