What are the general strategies in assessing new differentially methylation positions obtained from EWAS?
1
0
Entering edit mode
23 months ago
samuelandjw ▴ 250

In an epigenome-wide association study, a large number (100+) of significant differentially methylation positions (DMPs), would be identified, in contrast to GWAS, where most signals would be confined to small number of loci.

As a bioinformatician, when assessing the significant signals, I would just query the loci one by one manually to search for potential biological processes behind the trait under investigation since there would be just a few of them.

However, in EWAS, this is certainly not feasible as there could be more than 100 signals. I tried looking into the genes the DMPs mapped to according to the manifest file (by Illumina), but it is unclear how the CpG sites were mapped to that gene, and how methylation will affect the functions of the target gene. I tried pathway or GO term enrichment, but what I got were vague terms and I don't know how to follow up on enrichment analyses. I also tried looking for DMPs that are eQTMs, but eQTM resources are hard to find, and many DMPs are not eQTMs.

What are your general strategies in assessing DMPs to 1) find out DMPs that are worth pursuing and 2) search for the biological processes behind the DMPs?

methylation EWAS DNA • 473 views
ADD COMMENT
2
Entering edit mode
23 months ago
Basti ★ 2.0k

Personnally, I prefer focusing on DMRs because they capture the redundancy of close CpGs that may be present in your pool of DMPs. Usually you will have less DMRs than DMPs which could allow you to examine invidiually each DMRs. I think DMRs provide more robust and biological information than DMPs because, except in imprinted regions or age-related loci (and maybe specific cases that I am not aware of), a single DMP may not have a great effect on your condition of interest. However you could have a look at how your DMPs are distributed across the genome, are they preferentially located in promoters or CpG islands? This could be a hint that these CpGs are worth to investigate I can recommend you this paper to see current practices in analyzing methylation data : https://clinicalepigeneticsjournal.biomedcentral.com/track/pdf/10.1186/s13148-021-01200-8.pdf

If you want to perform gene ontology analysis, there is also a dedicated tool for DMPs in the missMethyl package (gometh) : https://bioconductor.org/packages/devel/bioc/vignettes/missMethyl/inst/doc/missMethyl.html#cpg-level-analysis

ADD COMMENT

Login before adding your answer.

Traffic: 2989 users visited in the last hour
Help About
FAQ
Access RSS
API
Stats

Use of this site constitutes acceptance of our User Agreement and Privacy Policy.

Powered by the version 2.3.6