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. 2018 Sep 17;19(Suppl 1):84.
doi: 10.1186/s12863-018-0637-4.

Comparison of novel and existing methods for detecting differentially methylated regions

Samantha Lent  1 , Hanfei Xu  2 , Lan Wang  2 , Zhe Wang  3 , Chloé Sarnowski  2 , Marie-France Hivert  4   5 , Josée Dupuis  2   3
Affiliations

Comparison of novel and existing methods for detecting differentially methylated regions

Samantha Lent et al. BMC Genet. .

Abstract

Background: Single-probe analyses in epigenome-wide association studies (EWAS) have identified associations between DNA methylation and many phenotypes, but do not take into account information from neighboring probes. Methods to detect differentially methylated regions (DMRs) (clusters of neighboring probes associated with a phenotype) may provide more power to detect associations between DNA methylation and diseases or phenotypes of interest.

Results: We proposed a novel approach, GlobalP, and perform comparisons with 3 methods-DMRcate, Bumphunter, and comb-p-to identify DMRs associated with log triglycerides (TGs) in real GAW20 data before and after fenofibrate treatment. We applied these methods to the summary statistics from an EWAS performed on the methylation data. Comb-p, DMRcate, and GlobalP detected very similar DMRs near the gene CPT1A on chromosome 11 in both the pre- and posttreatment data. In addition, GlobalP detected 2 DMRs before fenofibrate treatment in the genes ETV6 and ABCG1. Bumphunter identified several DMRs on chromosomes 1 and 20, which did not overlap with DMRs detected by other methods.

Conclusions: Our novel method detected the same DMR identified by two existing methods and detected two additional DMRs not identified by any of the existing methods we compared.

Keywords: DNA methylation; Differentially methylated regions; Epigenetics.

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Figures

Fig. 1
Fig. 1
Analysis results (−log 10 p value) and position of DMRs before (left panel) and after (right panel) treatment in the CPT1A region on chromosome 11. Points represent single CpG site results from the lmekin EWAS and points connected by lines represent DMRs, with each point representing a CpG site in the region. DMRcate and comb-p DMRs are labeled with genomic position and GlobalP DMRs are labeled with gene or CpG island annotation. Comb-p p values were corrected for multiple testing using a Sidak correction, and all other p values were corrected for multiple testing using an FDR
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References

    1. Yang X, Lay F, Han H, Jones PA. Targeting DNA methylation for epigenetic therapy. Trends Pharmacol Sci. 2010;31(11):536–546. doi: 10.1016/j.tips.2010.08.001. - DOI - PMC - PubMed
    1. Zhang Q, Zhao Y, Zhang R, Wei Y, Yi H, Shao F, Chen F. A comparative study of five association tests based on CpG set for epigenome-wide association studies. PLoS One. 2016;11(6):e0156895. doi: 10.1371/journal.pone.0156895. - DOI - PMC - PubMed
    1. Herman JG, Baylin SB. Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med. 2003;49(21):2042–2054. doi: 10.1056/NEJMra023075. - DOI - PubMed
    1. Peters TJ, Buckley MJ, Statham AL, Pidsley R, Samaras K, V Lord R, Clark SJ, Molloy PL. De novo identification of differentially methylated regions in the human genome. Epigenetics Chromatin. 2015;8:6. - PMC - PubMed
    1. Jaffe AE, Murakami P, Lee H, Leek JT, Fallin MD, Feinberg AP, Irizarry RA. Bump hunting to identify differentially methylated regions in epigenetic epidemiology studies. Int J Epidemiol. 2012;41(1):200–209. doi: 10.1093/ije/dyr238. - DOI - PMC - PubMed

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