Hello David,

I am back with an additional question :)
I have noticed that in my data set the vast majority of the mass shifts 
(outside the +/-0.02 Da window) are localized withing the fist 4 residues 
(from the n-term), except for position #2.
This is for a localization probability > 0.75, but it does not change if I 
use > 0.9, except for # 3 and 4 that tend to be slightly less frequent that 
position #1.
Have you noticed the same?

Thanks
-Piero

<https://lh3.googleusercontent.com/-pd1QudrhPDQ/W0MEr8yj6ZI/AAAAAAAAALQ/aPqqd0KQjBcjqI5-h7PAFnm5TrhL4dQXwCLcBGAs/s1600/loc.jpg>




On Monday, June 11, 2018 at 8:57:53 PM UTC+2, David Shteynberg wrote:
>
> Hello Piero.
>
> The reason mass shift localizations are performed on all amino acids is to 
> avoid any assumptions on the part of PTMProphet.  The goal of PTMProphet in 
> mass shift localization mode is to simply localize the mass shift without 
> assuming anything else about the modification.  This can help the user 
> discover rare modifications.  For instance, phosphorylation on D is listed 
> as a rare modification in unimod.
>
> Cheers,
>
> -David
>
> On Mon, Jun 11, 2018 at 9:40 AM, Piero Giansanti <[email protected] 
> <javascript:>> wrote:
>
>> That worked out, eventually :)
>>
>> I have an additional question though, which comes from the fact that the 
>> majority of the known mass shift in my data set has not been fully 
>> localized on a specific residue, even when spectra look OK-ish.
>> My background is totally not bioinformatics/statistics, so this could be 
>> a silly question :) ...
>>
>> Anyway, is there a reason why the localization of the mass shift is 
>> performed differently compared the the localization of a known modification?
>> What I mean is that (as far as I understood), when one wants to perform 
>> localization on (phospho.STY)PEPTIDE, PTMprophet will simply return T4 as 
>> the phosphorylated residues (it will not even try to look at D6),
>> but when trying on (+79.966Da)PEPTIDE, PTMprophet will not focus on just 
>> T and D, but rather 'look' at the entire sequence.
>>
>> Wouldn't this 'focusing' speed up the time need for the localization, and 
>> boost the localization rate?
>>
>> Thanks
>> -Piero
>>
>>
>>
>>
>> On Tuesday, May 22, 2018 at 6:43:33 PM UTC+2, David Shteynberg wrote:
>>>
>>> If you are able to build the TPP the code has been checked into the SVN 
>>> repository.  You can find the code here:
>>>
>>>
>>> https://sourceforge.net/p/sashimi/code/HEAD/tree/trunk/trans_proteomic_pipeline/
>>>
>>> If not I can send you a precompiled executable.  Which linux flavor are 
>>> you using?
>>>
>>> -David
>>>
>>> On Tue, May 22, 2018 at 5:40 AM, Piero Giansanti <[email protected]> 
>>> wrote:
>>>
>>>> Hello David,
>>>>
>>>> Just tried with TPP 5.1.0 (linux), but same problem as you can see 
>>>> below.
>>>> Is there a way to get hands on the version you have used? :)
>>>>
>>>> <spectrum_query start_scan="3214" assumed_charge="2" 
>>>> spectrum="01928_GA1_P020123_S00_R01_R1.03214.03214.2" end_scan="3214" 
>>>> index="6" precursor_neutral_mass="1247.5479" retention_time_sec="1120.817">
>>>> <search_result>
>>>> <search_hit peptide="GGMNGASPPTSQK" massdiff="0.9869" 
>>>> calc_neutral_pep_mass="1246.5610" peptide_next_aa="D" 
>>>> num_missed_cleavages="0" num_tol_term="2" num_tot_proteins="1" 
>>>> tot_num_ions="24" hit_rank="1" num_matched_ions="10" 
>>>> protein="sp|Q62234|MYOM1_MOUSE" peptide_prev_aa="R" is_rejected="0" 
>>>> protein_descr="Myomesin-1 OS=Mus musculus OX=10090 GN=Myom1 PE=1 SV=2">
>>>> <modification_info modified_peptide="G[58]GM[147]NGASPPTSQK">
>>>> <mod_aminoacid_mass position="1" mass="58.00836"/>
>>>> <mod_aminoacid_mass position="3" mass="147.0354"/>
>>>> </modification_info>
>>>> <search_score name="hyperscore" value="21.034"/>
>>>> <search_score name="nextscore" value="18.157"/>
>>>> <search_score name="expect" value="1.601e-03"/>
>>>> <analysis_result analysis="peptideprophet">
>>>> <peptideprophet_result probability="0.9995" 
>>>> all_ntt_prob="(0.9840,0.9981,0.9995)">
>>>> <search_score_summary>
>>>> <parameter name="fval" value="5.8278"/>
>>>> <parameter name="ntt" value="2"/>
>>>> <parameter name="nmc" value="0"/>
>>>> <parameter name="massd" value="0.987"/>
>>>> </search_score_summary>
>>>> </peptideprophet_result>
>>>> </analysis_result>
>>>> <analysis_result analysis="ptmprophet">
>>>> <ptmprophet_result prior="0.0769231" 
>>>> ptm="PTMProphet_ABCDEFGHIJKLMNOPQRSTUVXWYZ0.9869" 
>>>> ptm_peptide="G(0.000)G(0.000)M(0.000)N(0.000)G(0.000)A(0.000)S(0.000)P(0.000)P(0.000)T(0.000)S(0.000)Q(0.000)K(0.000)">
>>>> <mod_aminoacid_probability position="1" probability="0.000"/>
>>>> <mod_aminoacid_probability position="2" probability="0.000"/>
>>>> <mod_aminoacid_probability position="3" probability="0.000"/>
>>>> <mod_aminoacid_probability position="4" probability="0.000"/>
>>>> <mod_aminoacid_probability position="5" probability="0.000"/>
>>>> <mod_aminoacid_probability position="6" probability="0.000"/>
>>>> <mod_aminoacid_probability position="7" probability="0.000"/>
>>>> <mod_aminoacid_probability position="8" probability="0.000"/>
>>>> <mod_aminoacid_probability position="9" probability="0.000"/>
>>>> <mod_aminoacid_probability position="10" probability="0.000"/>
>>>> <mod_aminoacid_probability position="11" probability="0.000"/>
>>>> <mod_aminoacid_probability position="12" probability="0.000"/>
>>>> <mod_aminoacid_probability position="13" probability="0.000"/>
>>>> </ptmprophet_result>
>>>> </analysis_result>
>>>> </search_hit>
>>>> </search_result>
>>>> </spectrum_query>
>>>>
>>>>
>>>>
>>>>
>>>> On Friday, May 18, 2018 at 6:58:36 PM UTC+2, David Shteynberg wrote:
>>>>>
>>>>> Hello Piero,
>>>>>
>>>>> It appears that the version of PTMProphet in Philosopher is a bit out 
>>>>> of date.  The latest TPP version is 5.1.0, and PTMProphet has been 
>>>>> updated 
>>>>> with bugfixes and new features in the meantime. I have run my latest 
>>>>> PTMProphet code (targeted for the 5.2.0 version of TPP) on your data.  
>>>>> For 
>>>>> the PSMs matching this peptide I cannot replicate the issue you've 
>>>>> reported.  Instead, PTMProphet seems to be positioning the mass 
>>>>> modification on the Asparagine in your peptide as you should see in the 
>>>>> following result file:
>>>>>
>>>>>
>>>>> https://www.dropbox.com/s/z3xf379ulljr3rr/01928_GA1_P020123_S00_R01_R1.PTMPro.pep.xml?dl=0
>>>>>
>>>>> Thanks for your interest in PTMProphet.
>>>>>
>>>>> Cheers!
>>>>>
>>>>> -David
>>>>>
>>>>> On Fri, May 18, 2018 at 8:40 AM, Piero Giansanti <[email protected]
>>>>> > wrote:
>>>>>
>>>>>> Hello David,
>>>>>>
>>>>>> I am using PTMprophet via philosopher, and from the xml output it 
>>>>>> seems it is this version
>>>>>> TPP v5.0.1 Post-Typhoon dev, Build 201706282113-exported 
>>>>>> (Linux-x86_64)
>>>>>>
>>>>>> Regarding the settings, I am using --massdiffmode --mztol 0.01. The 
>>>>>> mass tolerance is not exactly the one used for the database search (20 
>>>>>> ppm), but it should be somehow close to it.
>>>>>>
>>>>>> Here https://ufile.io/wiqqb the mzML, pepXML and the output I 
>>>>>> generated.
>>>>>>
>>>>>> Thanks
>>>>>>
>>>>>>
>>>>>> On Friday, May 18, 2018 at 4:21:27 PM UTC+2, David Shteynberg wrote:
>>>>>>>
>>>>>>> Hello Piero,
>>>>>>>
>>>>>>> Thank you for trying the software.  This is indeed an unusual 
>>>>>>> result.  Can you tell me which version of PTMProphet you are using and 
>>>>>>> how 
>>>>>>> you are running the tool?  Is it possible for you to post your pepXML 
>>>>>>> file 
>>>>>>> and data file online for me to download and test this particular ID?
>>>>>>>
>>>>>>> Cheers,
>>>>>>> -David
>>>>>>>
>>>>>>> On Fri, May 18, 2018 at 1:53 AM, Piero Giansanti <
>>>>>>> [email protected]> wrote:
>>>>>>>
>>>>>>>> Hi,
>>>>>>>>
>>>>>>>> I am using PTMprophet to localize the set of modifications (i.e. 
>>>>>>>> mass shifts) identified by running an open search with MSfragger, but 
>>>>>>>> I 
>>>>>>>> have some doubt regarding the interpretation of the output.
>>>>>>>> In particular, MSfragger identified this peptide
>>>>>>>> *GG(ox)MNGASPPTSQK*
>>>>>>>> with a mass shift of 0.9869 Da, which match to the following 
>>>>>>>> modification according to Unimod
>>>>>>>> 0.9840:Deamidated (Deamidation), 0.9840:Asn->Asp (Asn->Asp 
>>>>>>>> substitution), 0.9840:Gln->Glu (Gln->Glu substitution).
>>>>>>>>
>>>>>>>> Of these 3 only the first 2 are possible (there is no Q in the 
>>>>>>>> sequence, so there cannot be any Gln->Glu substitution).
>>>>>>>>
>>>>>>>> Now, the output of PTMprophet is as follows:
>>>>>>>>
>>>>>>>> *G(0.000)G(0.000)M(0.000)N(0.000)G(0.000)A(0.000)S(0.000)P(0.000)P(0.000)T(0.000)S(0.000)Q(0.000)K(0.000)*
>>>>>>>>
>>>>>>>> Is a probability always 0 somehow an expected behavior? How do I 
>>>>>>>> interpret this? Am I right to say that the 0.9869 Da shift cannot be 
>>>>>>>> localized to any residues?
>>>>>>>> My concerns comes from the fact that even if the mod cannot be 
>>>>>>>> localized, I would have expected to get a probability of (~0.008, i.e. 
>>>>>>>> 100/length of the peptides) for each residues...
>>>>>>>>
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>>>>>>>>
>>>>>>>
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>>>>>
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>>>
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