How to compute average methylation among multiple sites given raw sequencing reads
I have a question regarding calculating average methylation across all sites from one single gene. I have the raw data from chip bis sequencing in the following form.
Total reads, # of C reads, ratio
15, 5,0.33
20,5,0.4
10,5,05
My question is since the total number of reads at different sites is different, which would be a better way to compute average methylation?
- Take the ratio and divide by number of site?
- Take the sum of #of C reads among all sites/ sum of Total reads?
I am leaning towards method #2 since I feel like its a more accurate depiction of the raw data but I wanna hear some opinions!
Thanks!
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It's probably best to just take the weighted average. So for this "gene", you'd get:
0.33*(15/(15+20+10)) + 0.4*(20/(15+20+10)) + 0.5*(10/(15+20+10))
which is ~0.399.
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The simple average and the weighted average output the same methylation percentage
18/45 = 0.33*(15/(15+20+10)) + 0.4*(20/(15+20+10)) + 0.5*(10/(15+20+10))
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there is a typo - the second column should be 20,5,0.25