Question: Differentially methylated regions (DMRs) and sites (DMCs) are not in the same region
0
gravatar for rahel14350
2.2 years ago by
rahel1435030
United States
rahel1435030 wrote:

Dear all,

I have some RRBS data with very low coverage and high number of NAs which they are aligned with BSMAP (more than 900,000 rows contain NAs). I did try many different packages but in all of them the DMRs and DMcs are completely different for example if gene A is detected as significantly methylated DMR in promoter region, there is no DMC CpG sites assigned to this gene from significantly methylated DMC output. Do you have any idea it? Many thanks in advance for your suggestions, Rahel

methylkit rnbeads rrbs metilene • 1.3k views
ADD COMMENTlink modified 2.2 years ago by Devon Ryan96k • written 2.2 years ago by rahel1435030
4
gravatar for ATpoint
2.2 years ago by
ATpoint36k
Germany
ATpoint36k wrote:

That sounds like the aggregation of read counts for all CpG over the region lifts the statistical power to make a significant call. That is the problem with low-coverage data. I have only little experience with sparse datasets, but I think there is not much you can do if the data do not have the power to make single CpG calls.

ADD COMMENTlink modified 2.2 years ago • written 2.2 years ago by ATpoint36k

Thanks a lot for your reply. I was running all different packages and having the same result, now it is clear for me.

ADD REPLYlink written 2.2 years ago by rahel1435030
2
gravatar for Devon Ryan
2.2 years ago by
Devon Ryan96k
Freiburg, Germany
Devon Ryan96k wrote:

There's no reason to expect DMRs to overlap DMCs. As ATpoint aptly noted, DMR calling works by aggregating information across CpGs. Typically an individual CpG will not be sufficiently differentially methylated itself, but a region will be. DMCs themselves are less likely to have biological effects unless they clump into DMRs (there are exceptions to this when a transcription factor preferentially binds to a motif with a particular methylation state).

ADD COMMENTlink written 2.2 years ago by Devon Ryan96k

Many thanks for your reply. Now it is more clear for me why I have such an output.

ADD REPLYlink written 2.2 years ago by rahel1435030
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