I know the way MACS2 uses Poisson distribution to find the p value for the enrichment of a signal peak(observed) as compared to the local control signal(expected). My question is can we compare the p values of different experiments with different sequencing depth.
An experiment with higher sequencing depth will not just have high peak signal but will have high noise too and thus the p value might differ as I have demonstrated below by taking 2 cases.
Case 1) Observed = 40 , expected =30 , p value = 0.03230957
But let’s increase the sequencing depth by 10x in case 2,then the observed and expected signals will also increase roughly by 10x, thus the p value will be much more significant.
Case 2) Observed =400, expected= 300, p value = 0.00000001639443
In my research work, I am in a need to compare different Chip-Seq experiment with different sequencing depth(varying from 100million to 10 billion sequencing depth). How do you think I can compare the signal enrichment between 2 chip-seq experiment with different sequencing depths ?