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] <javascript:>> 
> 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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>>
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