PTMs and p-values question

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Jordan Force

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Dec 19, 2019, 11:31:18 AM12/19/19
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Hi all,

When computing exact p-values, how do you calculate the P_{a_i} in equation 9 of this paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159662/#FD9 when there are modified amino acids? That is, the frequencies of a modified amino acid.

Looking at the code in TideSearchApplication.cpp and active_peptide_queue.cpp, it looks like you build the index, and then use the peptides in the index to compute the amino acid frequencies. I'm assuming would result in basically the frequency between an unmodified amino acid and its modified counterpart(s). For example, if you had phosphorylation as an allowed modification, then serine would have half of its frequency go to S, and half go to S* (phosphorylated serine). Does this sound about right? 

Thanks,

Jordan

Rita Chupalov

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Dec 19, 2019, 5:04:01 PM12/19/19
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Hi Jordan,

I'm afraid it's not that simple. Modified AA frequency will depend in a complex way on original AA frequency and number of allowed modifications per peptide. Each peptide can have different number of the given AA residues , so modifying say, 1 S per peptide will produce 50% modified S frequency only for  peptides with exactly 2 serines.
More precisely, if P(l, n) is number of peptides in your proteome with length l and number of serine residues equal n then frequency of modified serine will be sum(P(l, n) * min(mods, m))/sum(P(l, n) * l) where summation goes over whole proteome.

Bill, please correct me if I'm wrong here.

Rita

Rita Chupalov

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Dec 19, 2019, 5:46:19 PM12/19/19
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Sorry, I should have looked at the crux code first. Please, disregard my previous post. You are correct, the modified AAs in the index are counted in the same way as unmodified ones which in most cases will result in frequency being split very close to 50-50 between modified and unmodified AAs. It might me slightly less than 50 for the modified AA when number of allowed mods is smaller than the number of the AA occurrence in a peptide but this should be pretty rare occasion because typical peptides are pretty short and repeated residues are not very common.


On Thursday, December 19, 2019 at 8:31:18 AM UTC-8, Jordan Force wrote:

Jordan Force

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Dec 30, 2019, 2:19:38 PM12/30/19
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Thanks!
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