Hi Alex,

PTMProphet by default will ignore any spectrum with less than 90%
probability (iProphet is used when available.)  You can change this by
setting the option MINPROB= when you run the tool.  Let me know if that
still fails for you.

Thanks,
-David



On Mon, Apr 6, 2020 at 3:27 PM Alex Zelter <[email protected]> wrote:

> I am running into a situation where MSFragger returns a massdiff but
> PTMProphet seems to ignore it. No modification_info or mod_aminoacid_mass
> position is reported by PTMProphet for some results, while for others
> things work as expected.
> Here are 2 PSMs as examples. I've included both MSFragger xml output and
> PTMProphet output. For scan number 49967 the open modification is localized
> and reported correctly by PTMProphet, but for scan 74042 that information
> is missing from the PTMProphet output, despite the MSFragger xml input
> being similar.
> Both the examples below are taken from the same results files and were
> thus treated identically. TPP v5.2.1-dev Flammagenitus, Build
> 202003241419-8041 was used.
> If you have any idea what might be causing this I'd be very grateful!
> Thanks,
> Alex
>
> MSFragger pep.xml output for scan 49967 (works as expected):
>
> <spectrum_query start_scan="49967"
> uncalibrated_precursor_neutral_mass="1847.0168" assumed_charge="3"
> spectrum="QEP2_2018_0812_AZ_033_az736_AZ.49967.49967.3" end_scan="49967"
> index="39256" precursor_neutral_mass="1847.0134"
> retention_time_sec="5830.280">
> <search_result>
> <search_hit peptide="VTKCCTESLVNR" massdiff="495.3547"
> calc_neutral_pep_mass="1351.6587" peptide_next_aa="R"
> num_missed_cleavages="1" num_tol_term="2" num_tot_proteins="10"
> tot_num_ions="44" hit_rank="1" num_matched_ions="9"
> protein="sp|P02768|ALBU_HUMAN Serum albumin OS=Homo sapiens GN=ALB PE=1
> SV=2" peptide_prev_aa="R" is_rejected="0">
> <alternative_protein protein="tr|A0A087WWT3|A0A087WWT3_HUMAN Isoform of
> P02768, Serum albumin OS=Homo sapiens GN=ALB PE=1 SV=1" peptide_prev_aa="R"
> peptide_next_aa="R" num_tol_term="2"/>
> <alternative_protein protein="tr|A0A0C4DGB6|A0A0C4DGB6_HUMAN Isoform of
> P02768, Serum albumin OS=Homo sapiens GN=ALB PE=1 SV=1" peptide_prev_aa="R"
> peptide_next_aa="R" num_tol_term="2"/>
> <alternative_protein protein="tr|B7WNR0|B7WNR0_HUMAN Isoform of P02768,
> Serum albumin OS=Homo sapiens GN=ALB PE=1 SV=1" peptide_prev_aa="R"
> peptide_next_aa="R" num_tol_term="2"/>
> <alternative_protein protein="tr|C9JKR2|C9JKR2_HUMAN Isoform of P02768,
> Albumin, isoform CRA_k OS=Homo sapiens GN=ALB PE=1 SV=1"
> peptide_prev_aa="R" peptide_next_aa="R" num_tol_term="2"/>
> <alternative_protein protein="tr|D6RHD5|D6RHD5_HUMAN Isoform of P02768,
> Serum albumin OS=Homo sapiens GN=ALB PE=1 SV=1" peptide_prev_aa="R"
> peptide_next_aa="R" num_tol_term="2"/>
> <alternative_protein protein="tr|H0YA55|H0YA55_HUMAN Isoform of P02768,
> Serum albumin (Fragment) OS=Homo sapiens GN=ALB PE=1 SV=1"
> peptide_prev_aa="R" peptide_next_aa="R" num_tol_term="2"/>
> <alternative_protein protein="sp|P02768-2|ALBU_HUMAN Isoform of P02768,
> Isoform 2 of Serum albumin OS=Homo sapiens GN=ALB" peptide_prev_aa="R"
> peptide_next_aa="R" num_tol_term="2"/>
> <alternative_protein protein="sp|P02768-3|ALBU_HUMAN Isoform of P02768,
> Isoform 3 of Serum albumin OS=Homo sapiens GN=ALB" peptide_prev_aa="R"
> peptide_next_aa="R" num_tol_term="2"/>
> <alternative_protein protein="sp|ALBU_BOVIN|" peptide_prev_aa="R"
> peptide_next_aa="R" num_tol_term="2"/>
> <search_score name="hyperscore" value="15.283"/>
> <search_score name="nextscore" value="12.987"/>
> <search_score name="expect" value="1.670e-04"/>
> </search_hit>
> </search_result>
> </spectrum_query>
>
> PTMProphet output for the scan 49967:
> <spectrum_query start_scan="49967"
> uncalibrated_precursor_neutral_mass="1847.0168" assumed_charge="3"
> spectrum="QEP2_2018_0812_AZ_033_az736_AZ.49967.49967.3" end_scan="49967"
> index="34348" precursor_neutral_mass="1847.0134"
> retention_time_sec="5830.280">
> <search_result>
> <search_hit peptide="VTKCCTESLVNR" massdiff="495.3547"
> calc_neutral_pep_mass="1351.6587" peptide_next_aa="R"
> num_missed_cleavages="1" num_tol_term="2" num_tot_proteins="10"
> tot_num_ions="44" hit_rank="1" num_matched_ions="9"
> protein="sp|P02768|ALBU_HUMAN" peptide_prev_aa="R" is_rejected="0"
> protein_descr="Serum albumin OS=Homo sapiens GN=ALB PE=1 SV=2">
> <alternative_protein protein="tr|A0A087WWT3|A0A087WWT3_HUMAN"
> protein_descr="Isoform of P02768, Serum albumin OS=Homo sapiens GN=ALB PE=1
> SV=1" num_tol_term="2" peptide_prev_aa="R" peptide_next_aa="R"/>
> <alternative_protein protein="tr|A0A0C4DGB6|A0A0C4DGB6_HUMAN"
> protein_descr="Isoform of P02768, Serum albumin OS=Homo sapiens GN=ALB PE=1
> SV=1" num_tol_term="2" peptide_prev_aa="R" peptide_next_aa="R"/>
> <alternative_protein protein="tr|B7WNR0|B7WNR0_HUMAN"
> protein_descr="Isoform of P02768, Serum albumin OS=Homo sapiens GN=ALB PE=1
> SV=1" num_tol_term="2" peptide_prev_aa="R" peptide_next_aa="R"/>
> <alternative_protein protein="tr|C9JKR2|C9JKR2_HUMAN"
> protein_descr="Isoform of P02768, Albumin, isoform CRA_k OS=Homo sapiens
> GN=ALB PE=1 SV=1" num_tol_term="2" peptide_prev_aa="R" peptide_next_aa="R"/>
> <alternative_protein protein="tr|D6RHD5|D6RHD5_HUMAN"
> protein_descr="Isoform of P02768, Serum albumin OS=Homo sapiens GN=ALB PE=1
> SV=1" num_tol_term="2" peptide_prev_aa="R" peptide_next_aa="R"/>
> <alternative_protein protein="tr|H0YA55|H0YA55_HUMAN"
> protein_descr="Isoform of P02768, Serum albumin (Fragment) OS=Homo sapiens
> GN=ALB PE=1 SV=1" num_tol_term="2" peptide_prev_aa="R" peptide_next_aa="R"/>
> <alternative_protein protein="sp|P02768-2|ALBU_HUMAN"
> protein_descr="Isoform of P02768, Isoform 2 of Serum albumin OS=Homo
> sapiens GN=ALB" num_tol_term="2" peptide_prev_aa="R" peptide_next_aa="R"/>
> <alternative_protein protein="sp|P02768-3|ALBU_HUMAN"
> protein_descr="Isoform of P02768, Isoform 3 of Serum albumin OS=Homo
> sapiens GN=ALB" num_tol_term="2" peptide_prev_aa="R" peptide_next_aa="R"/>
> <alternative_protein protein="sp|ALBU_BOVIN|" num_tol_term="2"
> peptide_prev_aa="K" peptide_next_aa="R"/>
> <search_score name="hyperscore" value="15.283"/>
> <search_score name="nextscore" value="12.987"/>
> <search_score name="expect" value="1.670e-04"/>
> <analysis_result analysis="peptideprophet">
> <peptideprophet_result probability="0.9495"
> all_ntt_prob="(0.0000,0.0020,0.9495)">
> <search_score_summary>
> <parameter name="fval" value="6.0889"/>
> <parameter name="ntt" value="2"/>
> <parameter name="nmc" value="1"/>
> <parameter name="massd" value="-0.303"/>
> <parameter name="isomassd" value="3"/>
> </search_score_summary>
> </peptideprophet_result>
> </analysis_result>
> <analysis_result analysis="interprophet">
> <interprophet_result probability="0.919585"
> all_ntt_prob="(0,0.00121737,0.919585)">
> <search_score_summary>
> <parameter name="nrs" value="-8.8028"/>
> <parameter name="nsi" value="0.999"/>
> <parameter name="nsm" value="2.9825"/>
> <parameter name="nsp" value="20"/>
> </search_score_summary>
> </interprophet_result>
> </analysis_result>
> *<modification_info modified_peptide="VTK[623]CCTESLVNR">*
> *<mod_aminoacid_mass position="3" mass="623.4497"/>*
> </modification_info>
> <analysis_result analysis="ptmprophet">
> <parameter name="mass_ppm_offset" value="-2.43401"/>
> <parameter name="mass_ppm_tolerance" value="11.2026"/>
> <ptmprophet_result ptm="MASSDIFF" prior="0.0833333"
> ptm_peptide="V(0.024)T(0.024)K(0.777)C(0.035)C(0.035)T(0.023)E(0.018)S(0.015)L(0.013)V(0.013)N(0.011)R(0.011)">
> <parameter name="mean_best_prob" value="0.777"/>
> <parameter name="norm_info_gain" value="0.580"/>
> <parameter name="localized_mods" value="0.580"/>
> <mod_aminoacid_probability position="1" probability="2.436e-02"
> oscore="0.071" mscore="0.250" direct_oscore="0.500" direct_mscore="0.500"
> cterm_score="0.500" nterm_score="0.000"/>
> <mod_aminoacid_probability position="2" probability="2.436e-02"
> oscore="0.071" mscore="0.250" direct_oscore="0.500" direct_mscore="0.500"
> cterm_score="0.500" nterm_score="0.000"/>
> <mod_aminoacid_probability position="3" probability="7.774e-01"
> oscore="0.928" mscore="0.667" direct_oscore="0.500" direct_mscore="0.500"
> cterm_score="0.500" nterm_score="0.000"/>
> <mod_aminoacid_probability position="4" probability="3.531e-02"
> oscore="0.072" mscore="0.333" direct_oscore="0.500" direct_mscore="0.500"
> cterm_score="0.500" nterm_score="0.000"/>
> <mod_aminoacid_probability position="5" probability="3.531e-02"
> oscore="0.072" mscore="0.333" direct_oscore="0.500" direct_mscore="0.500"
> cterm_score="0.500" nterm_score="0.000"/>
> <mod_aminoacid_probability position="6" probability="2.256e-02"
> oscore="0.043" mscore="0.250" direct_oscore="0.500" direct_mscore="0.500"
> cterm_score="0.462" nterm_score="0.000"/>
> <mod_aminoacid_probability position="7" probability="1.758e-02"
> oscore="0.033" mscore="0.200" direct_oscore="0.500" direct_mscore="0.500"
> cterm_score="0.417" nterm_score="0.000"/>
> <mod_aminoacid_probability position="8" probability="1.491e-02"
> oscore="0.025" mscore="0.167" direct_oscore="0.500" direct_mscore="0.500"
> cterm_score="0.364" nterm_score="0.000"/>
> <mod_aminoacid_probability position="9" probability="1.349e-02"
> oscore="0.024" mscore="0.143" direct_oscore="0.500" direct_mscore="0.500"
> cterm_score="0.300" nterm_score="0.000"/>
> <mod_aminoacid_probability position="10" probability="1.255e-02"
> oscore="0.023" mscore="0.125" direct_oscore="0.500" direct_mscore="0.500"
> cterm_score="0.222" nterm_score="0.000"/>
> <mod_aminoacid_probability position="11" probability="1.131e-02"
> oscore="0.019" mscore="0.100" direct_oscore="0.101" direct_mscore="0.333"
> cterm_score="0.000" nterm_score="0.000"/>
> <mod_aminoacid_probability position="12" probability="1.082e-02"
> oscore="0.014" mscore="0.091" direct_oscore="0.101" direct_mscore="0.333"
> cterm_score="0.000" nterm_score="0.000"/>
> </ptmprophet_result>
> </analysis_result>
> </search_hit>
> </search_result>
> </spectrum_query>
>
>
>
> MSFragger pep.xml output for scan 74042 (does not work as expected):
> <spectrum_query start_scan="74042"
> uncalibrated_precursor_neutral_mass="1494.4763" assumed_charge="2"
> spectrum="QEP2_2018_0812_AZ_033_az736_AZ.74042.74042.2" end_scan="74042"
> index="61738" precursor_neutral_mass="1494.4722"
> retention_time_sec="8409.789">
> <search_result>
> <search_hit peptide="VTKCCTESLVNR" massdiff="142.8135"
> calc_neutral_pep_mass="1351.6587" peptide_next_aa="R"
> num_missed_cleavages="1" num_tol_term="2" num_tot_proteins="10"
> tot_num_ions="22" hit_rank="1" num_matched_ions="11"
> protein="sp|P02768|ALBU_HUMAN Serum albumin OS=Homo sapiens GN=ALB PE=1
> SV=2" peptide_prev_aa="R" is_rejected="0">
> <alternative_protein protein="tr|A0A087WWT3|A0A087WWT3_HUMAN Isoform of
> P02768, Serum albumin OS=Homo sapiens GN=ALB PE=1 SV=1" peptide_prev_aa="R"
> peptide_next_aa="R" num_tol_term="2"/>
> <alternative_protein protein="tr|A0A0C4DGB6|A0A0C4DGB6_HUMAN Isoform of
> P02768, Serum albumin OS=Homo sapiens GN=ALB PE=1 SV=1" peptide_prev_aa="R"
> peptide_next_aa="R" num_tol_term="2"/>
> <alternative_protein protein="tr|B7WNR0|B7WNR0_HUMAN Isoform of P02768,
> Serum albumin OS=Homo sapiens GN=ALB PE=1 SV=1" peptide_prev_aa="R"
> peptide_next_aa="R" num_tol_term="2"/>
> <alternative_protein protein="tr|C9JKR2|C9JKR2_HUMAN Isoform of P02768,
> Albumin, isoform CRA_k OS=Homo sapiens GN=ALB PE=1 SV=1"
> peptide_prev_aa="R" peptide_next_aa="R" num_tol_term="2"/>
> <alternative_protein protein="tr|D6RHD5|D6RHD5_HUMAN Isoform of P02768,
> Serum albumin OS=Homo sapiens GN=ALB PE=1 SV=1" peptide_prev_aa="R"
> peptide_next_aa="R" num_tol_term="2"/>
> <alternative_protein protein="tr|H0YA55|H0YA55_HUMAN Isoform of P02768,
> Serum albumin (Fragment) OS=Homo sapiens GN=ALB PE=1 SV=1"
> peptide_prev_aa="R" peptide_next_aa="R" num_tol_term="2"/>
> <alternative_protein protein="sp|P02768-2|ALBU_HUMAN Isoform of P02768,
> Isoform 2 of Serum albumin OS=Homo sapiens GN=ALB" peptide_prev_aa="R"
> peptide_next_aa="R" num_tol_term="2"/>
> <alternative_protein protein="sp|P02768-3|ALBU_HUMAN Isoform of P02768,
> Isoform 3 of Serum albumin OS=Homo sapiens GN=ALB" peptide_prev_aa="R"
> peptide_next_aa="R" num_tol_term="2"/>
> <alternative_protein protein="sp|ALBU_BOVIN|" peptide_prev_aa="R"
> peptide_next_aa="R" num_tol_term="2"/>
> <search_score name="hyperscore" value="19.365"/>
> <search_score name="nextscore" value="17.327"/>
> <search_score name="expect" value="1.083e-05"/>
> </search_hit>
> </search_result>
> </spectrum_query>
>
> PTMProphet pep.xml output for scan 74042 (does not work as expected):
> <spectrum_query start_scan="74042"
> uncalibrated_precursor_neutral_mass="1494.4763" assumed_charge="2"
> spectrum="QEP2_2018_0812_AZ_033_az736_AZ.74042.74042.2" end_scan="74042"
> index="54976" precursor_neutral_mass="1494.4722"
> retention_time_sec="8409.789">
> <search_result>
> <search_hit peptide="VTKCCTESLVNR" massdiff="142.8135"
> calc_neutral_pep_mass="1351.6587" peptide_next_aa="R"
> num_missed_cleavages="1" num_tol_term="2" num_tot_proteins="10"
> tot_num_ions="22" hit_rank="1" num_matched_ions="11"
> protein="sp|P02768|ALBU_HUMAN" peptide_prev_aa="R" is_rejected="0"
> protein_descr="Serum albumin OS=Homo sapiens GN=ALB PE=1 SV=2">
> <alternative_protein protein="tr|A0A087WWT3|A0A087WWT3_HUMAN"
> protein_descr="Isoform of P02768, Serum albumin OS=Homo sapiens GN=ALB PE=1
> SV=1" num_tol_term="2" peptide_prev_aa="R" peptide_next_aa="R"/>
> <alternative_protein protein="tr|A0A0C4DGB6|A0A0C4DGB6_HUMAN"
> protein_descr="Isoform of P02768, Serum albumin OS=Homo sapiens GN=ALB PE=1
> SV=1" num_tol_term="2" peptide_prev_aa="R" peptide_next_aa="R"/>
> <alternative_protein protein="tr|B7WNR0|B7WNR0_HUMAN"
> protein_descr="Isoform of P02768, Serum albumin OS=Homo sapiens GN=ALB PE=1
> SV=1" num_tol_term="2" peptide_prev_aa="R" peptide_next_aa="R"/>
> <alternative_protein protein="tr|C9JKR2|C9JKR2_HUMAN"
> protein_descr="Isoform of P02768, Albumin, isoform CRA_k OS=Homo sapiens
> GN=ALB PE=1 SV=1" num_tol_term="2" peptide_prev_aa="R" peptide_next_aa="R"/>
> <alternative_protein protein="tr|D6RHD5|D6RHD5_HUMAN"
> protein_descr="Isoform of P02768, Serum albumin OS=Homo sapiens GN=ALB PE=1
> SV=1" num_tol_term="2" peptide_prev_aa="R" peptide_next_aa="R"/>
> <alternative_protein protein="tr|H0YA55|H0YA55_HUMAN"
> protein_descr="Isoform of P02768, Serum albumin (Fragment) OS=Homo sapiens
> GN=ALB PE=1 SV=1" num_tol_term="2" peptide_prev_aa="R" peptide_next_aa="R"/>
> <alternative_protein protein="sp|P02768-2|ALBU_HUMAN"
> protein_descr="Isoform of P02768, Isoform 2 of Serum albumin OS=Homo
> sapiens GN=ALB" num_tol_term="2" peptide_prev_aa="R" peptide_next_aa="R"/>
> <alternative_protein protein="sp|P02768-3|ALBU_HUMAN"
> protein_descr="Isoform of P02768, Isoform 3 of Serum albumin OS=Homo
> sapiens GN=ALB" num_tol_term="2" peptide_prev_aa="R" peptide_next_aa="R"/>
> <alternative_protein protein="sp|ALBU_BOVIN|" num_tol_term="2"
> peptide_prev_aa="K" peptide_next_aa="R"/>
> <search_score name="hyperscore" value="19.365"/>
> <search_score name="nextscore" value="17.327"/>
> <search_score name="expect" value="1.083e-05"/>
> <analysis_result analysis="peptideprophet">
> <peptideprophet_result probability="0.9504"
> all_ntt_prob="(0.0000,0.9728,0.9504)">
> <search_score_summary>
> <parameter name="fval" value="6.1669"/>
> <parameter name="ntt" value="2"/>
> <parameter name="nmc" value="1"/>
> <parameter name="massd" value="0.337"/>
> <parameter name="isomassd" value="3"/>
> </search_score_summary>
> </peptideprophet_result>
> </analysis_result>
> <analysis_result analysis="interprophet">
> <interprophet_result probability="0.865139"
> all_ntt_prob="(0,0.922921,0.865139)">
> <search_score_summary>
> <parameter name="nrs" value="-15"/>
> <parameter name="nsi" value="0.9975"/>
> <parameter name="nsm" value="2.9825"/>
> <parameter name="nsp" value="20"/>
> </search_score_summary>
> </interprophet_result>
> </analysis_result>
> </search_hit>
> </search_result>
> </spectrum_query>
>
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