The Tandem API states that it can’t handle more than one variable modification 
on a given residue. See: http://thegpm.org/TANDEM/api/rpmm.html 
<http://thegpm.org/TANDEM/api/rpmm.html>.  There is a work-around in that 
document where you specify e.g. the light as a static mod and the difference 
between the heavy and light as a variable mod for a given residue.  So I don’ 
think your triple label search will work with Tandem unless you do three 
different searches, one for each label and use PeptideProphet to combine them 
into a single pepXML file for input to ProteinProphet.

Then there is Comet.  I’ve been using the version of Comet in TPP 4.8 and it 
seems to work nicely with  multiple variable modifications on the same residue. 
 I’m only using a dual di-methyl labeling strategy.  Not sure if it would work 
with triple labeled, but the parameter inputs allow for up to 9 variable mods 
to be specified:  
http://comet-ms.sourceforge.net/parameters/parameters_201501/variable_mod01.php 
<http://comet-ms.sourceforge.net/parameters/parameters_201501/variable_mod01.php>

How are you planning on doing the quantification once you get the searches to 
go successfully?

Cheers,

Brian

> On Apr 21, 2015, at 5:55 AM, Alejandro <[email protected]> wrote:
> 
> Hello all,
> 
> I have some experiments in which the samples were triple dimethyl labeled. 
> Does any of you have any tips on how to analyze these data with later version 
> of TPP? 
> 
> I looked through the list but only could find a couple of posts.
> 
> So far my ideas would be to do:
> 
> 1. Static searches of Heavy, Medium and Light and then analyze H/M, and H/L, 
> and deduce the M/L by dividing the ratios of (H/L)/(H/L) ?
> 
> So far I'm doing that, however after Peptide/ProteinProphet the results of 
> each vary quite abit and might end up with peptides/proteins with a ratio in 
> just two conditions and not in the three. Usually this also happens in 
> MaxQuant in triple labeled but only in very few hits.
> 
> 2. Would it be possible to run a variable search for all three modifications 
> in XTandem in one run, Heavy, Medium, Light and then just process H/M and H/L 
> with Peptide/ProteinProphet?
> 
> 
> Maybe some of you had any experience with this, any tips or help would be 
> appreciated!
> 
> Thanks,
> 
> Alejandro
> 
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