How to define and/or identify Partially methylated domain (DNA methylation)

Question

[smk]

How to identify or define Partially methylated domains given processed DNA methylation data with per cpg methylation score. Are there any tools that can help achieve that.

Answer 1

[yupeng he]

PMD is a methylation feature that is not well defined. There are many ways of calling it. The most convenient one should be MethylSeekR.

If you are interested,

1. In the paper where the concept of PMD was first introduced:

   A sliding window approach was used to find regions of the genome in IMR90 that were partially methylated, based on the measurements of the level of methylation at each mCG. A window size of 10 kb was used, progressing 10 kb per iteration. When a 10 kb window was identified that contained at least 10 mCG, each covered by at least 5 MethylC-Seq reads, for which the average methylation level of these mCG was less than 70%, the region was extended in 10 kb increments. Extension was terminated when a 10 kb increment was reached that had an average methylation level of greater than 70% or less than 10 mCG, and the region was reported as a PMD.

2. Also, HMM-based approach described in this paper.

3. In one most recent paper, random forest based approach

Answer 2

[Shicheng Guo]

It's the confusion time. In the field of DNA methylation, we created so many conceptions, however, we actually do not have the precise definition, functions and the code.

Answer 3

[Devon Ryan]

Well, partially methylated just means somewhere between the minimum and maximum (though we'd normally set some threshold like "in the middle 50%"). One question becomes how the methylation scores relate to absolute methylation. For example, if the scores end up being similar to the logit of the absolute score, then you'd filter at different threshold than if they were just an approximate linear mapping. Your task, then, will be to try to determine this, likely with a published dataset that also has paired bisulfite sequencing samples, and then filter accordingly.

[Saad Murtaza Khan]

Hi,

I am working with some of the public datasets for which the only information available is a wig file. Which looks like this :-

track type=wiggle_0 name="H1 combined" visibility=full color=20,150,20 altColor=150,20,20 windowingFunction=mean
variableStep chrom=chr1
10469 0.766666666666667
10470 0.766666666666667
10471 0.896551724137931
10472 0.896551724137931
10484 0.862068965517241
10485 0.862068965517241
10489 0.939393939393939
10490 0.939393939393939
10493 0.733333333333333
10494 0.733333333333333
10497 0.848484848484849
10498 0.848484848484849
10525 0.942857142857143
10526 0.942857142857143
10542 0.909090909090909
10543 0.909090909090909
10563 0.909090909090909
10564 0.909090909090909
10571 0.947368421052632
10572 0.947368421052632

How can I find Partially methylated regions for such files?

What window or stepsize should I use?

[Devon Ryan]

It just depends on what sort of region size you want to look at. There is no predefined definition for this.

[smk]

So should I calculate sizes of PMD varying sliding windows. The mean size of PMD is around 150 kb.