Thanks Alex.  I suspect it is a possible bug in PTMProphet. Can you see
what step of your analysis created these additional mods on C?  I would
help me narrow down the places to look.

Cheers,
David

On Wed, Mar 18, 2020 at 11:56 AM Alex Zelter <[email protected]> wrote:

> Hi David,
> Thanks for the fast response!
>
> My list of commands are as follows (after running MSFragger):
>
> tpp/bin/InteractParser       interact.pep.xml FraggerOutput.pepXML
> tpp/bin/DatabaseParser       interact.pep.xml
> tpp/bin/RefreshParser        interact.pep.xml
> /path/to/database/fastaFile.fasta
> tpp/bin/PeptideProphetParser interact.pep.xml ACCMASS DECOYPROBS
> DECOY=random NONPARAM MASSWIDTH=520 MINPROB=0
> tpp/bin/InterProphetParser   interact.pep.xml interact.ipro.pep.xml
> tpp/bin/PTMProphetParser MASSDIFFMODE interact.pep.xml
> tpp/bin/PTMProphetParser MASSDIFFMODE interact.ipro.pep.xml
>
> I'm happy to share the full set of files with you if that helps.
>
> Thanks!
> Alex
>
> On Wednesday, March 18, 2020 at 11:42:22 AM UTC-7, David Shteynberg wrote:
>>
>> Hi Alex,
>>
>> This seems like a bug that should be fixed.  Are you running PTMProphet
>> at any point in your analysis pipeline?
>>
>> Thanks,
>> -David
>>
>> On Wed, Mar 18, 2020 at 11:38 AM Alex Zelter <[email protected]> wrote:
>>
>>> I am running PTMProphet (TPP v5.2.1-dev Flammagenitus, Build
>>> 202003100907-8034) on MSFragger (MSFragger version MSFragger-2.3) output
>>> and ending up with strange results in specific cases.
>>>
>>> For example, for a specific PSM, 52782, MSFragger outputs:
>>>
>>> <spectrum_query start_scan="52782"
>>> uncalibrated_precursor_neutral_mass="2288.8486" assumed_charge="3"
>>> spectrum="QEP2_2018_0812_AZ_033_az736_AZ.52782.52782.3" end_scan="52782"
>>> index="41840" precursor_neutral_mass="2288.8384"
>>> retention_time_sec="6104.521">
>>> <search_result>
>>> <search_hit peptide="RYKAAFTECCQAADK" massdiff="471.0195"
>>> calc_neutral_pep_mass="1817.8188" peptide_next_aa="A"
>>> num_missed_cleavages="2" num_tol_term="2" num_tot_proteins="5"
>>> tot_num_ions="56" hit_rank="1" num_matched_ions="23"
>>> protein="sp|P02768|ALBU_HUMAN Serum albumin OS=Homo sapiens GN=ALB PE=1
>>> SV=2" peptide_prev_aa="K" is_rejected="0">
>>> <modification_info>
>>> <mod_aminoacid_mass mass="160.0307" position="9"/>
>>> <mod_aminoacid_mass mass="160.0307" position="10"/>
>>> </modification_info>
>>> <search_score name="hyperscore" value="44.421"/>
>>> <search_score name="nextscore" value="12.357"/>
>>> <search_score name="expect" value="4.415e-15"/>
>>> </search_hit>
>>> </search_result>
>>> </spectrum_query>
>>>
>>> This would indicate that C9 is +57, C10 is +57 and there is an
>>> additional unlocalized mass diff of +471.
>>>
>>> After running TPP I end up with output like this
>>> in interact.ipro.pep.xml for that scan:
>>>
>>> <spectrum_query start_scan="52782"
>>> uncalibrated_precursor_neutral_mass="2288.8486" assumed_charge="3"
>>> spectrum="QEP2_2018_0812_AZ_033_az736_AZ.52782.52782.3" end_scan="52782"
>>> index="36796" precursor_neutral_mass="2288.8384"
>>> retention_time_sec="6104.521">
>>> <search_result>
>>> <search_hit peptide="RYKAAFTECCQAADK" massdiff="471.0195"
>>> calc_neutral_pep_mass="1817.8188" peptide_next_aa="A"
>>> num_missed_cleavages="1" num_tol_term="2" num_tot_proteins="5"
>>> tot_num_ions="56" hit_rank="1" num_matched_ions="23"
>>> protein="sp|P02768|ALBU_HUMAN" peptide_prev_aa="K" is_rejected="0"
>>> protein_descr="Serum albumin OS=Homo sapiens GN=ALB PE=1 SV=2">
>>> <modification_info modified_peptide="RYKAAF[618]TEC[160]C[160]QAADK">
>>> <mod_aminoacid_mass position="6" mass="618.0879"/>
>>> <mod_aminoacid_mass position="9" mass="574.0287"/>
>>> <mod_aminoacid_mass position="10" mass="574.0287"/>
>>> </modification_info>.......
>>>
>>> So it seems to me that we now have a modification mass addition of +471
>>> on residues 6 9 and 10 rather than a mass addition of +471 on residue 6 and
>>> then an addition of +57 on residues 9 and 10.
>>>
>>> In cases where there is just a mass diff (open modification) and no
>>> defined variable modifications output is as expected. This situation seems
>>> to occur when both defined variable modifications and open modifications
>>> are present.
>>>
>>> I have confirmed the same behavior in older versions of MSFragger and
>>> TPP.
>>>
>>> Any ideas would be much appreciated!
>>> Thanks,
>>> Alex
>>>
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