Robert,

If you haven't solved this already in the 2 weeks since you posted,
you should focus on getting better scoring X!Tandem search results.
For the two peptides of interest, OMSSA returns expectation scores of
1E-4 and 4E-6 (lower=better).  But the X!Tandem expectation scores for
these peptides range from 0.22 to values greater than 1.0.  That's
where your problem is, not in optimizing PeptideProphet run options.
Figure out how to optimize your X!Tandem search parameters first.

On Aug 11, 7:34 am, Robert <[email protected]> wrote:
> Hi,
>
> I´m using OMSSA and the TPP/X!Tandem search (+TPP PeptideProphet/
> ProteinProphet) for LC-MS/MS data analysis.
>
> First, I always run OMSSA due to its high performance to have first
> information on the sample (for curious colleagues, and to set
> priorities), then I make a more thorough analysis using the TPP.
>
> However, OMSSA reports some different peptides as the final TPP
> output.
>
> When looking at the *.pep.xml, all peptides found by OMSSA, are also
> present in the X!/Tandem-pep.xml file, but not reported at the end of
> the pipeline. I already tried to set the p-filter for the
> PeptideProphet to very low values (0.0001), but those additional
> peptides do not show up.
>
> Example for the trypsin precursor:
>
> TPP reports:
> **************
>
> 7       gi|136406|sp|P06871.1|TRY1_CANFA  gi|136429|sp|P00761.1|TRYP_PIG
> 0.9565
>
> confidence: 0.28        max coverage: 4.3%      num unique peps: 1      tot 
> indep
> spectra: 1      share of spectrum id's: 1.84%
>
>         >RecName: Full=Cationic trypsin; Flags: Precursor    Length: 246aa
>
>         >RecName: Full=Trypsin; Flags: Precursor
>
>                 weight  peptide sequence        nsp adj prob    init prob     
>   ntt     nsp     total   pep grp
> ind
>
>         *       wt-1.00         2_LSSPATLNSR    0.9565  0.9851  2       0.00  
>   1
>
> OMSSA reports (top redundant hits):
> ******************************************
>
> Peptide:        IITHPnFNGNTLDNDIMLIK    Neutral Mass:     2283.3 Da     
> Charge State:
> +3      E-value:        1.203E-006
>
> Peptide:        LGEHNIDVLEGNEQFINAAK    Neutral Mass:     2211.5 Da     
> Charge State:
> +3      E-value:        4.363E-009
>
> In both searches I included deamidation of Q/N
>
> Searching those peptides in the TPP *.pep.xml gives:
> *************************************************************
>
> index   spectrum        hyperscore      nextscore       bscore  yscore  
> expect  ions
> peptide         protein
> 1331    3D-1.01138.01138.3SpectraST     637     558     1       1       0.22  
>   38/76
> R.LGEHNIDVLEGNEQFINAAK.IPeptideAtlas    gi|136429|sp|P00761.1|TRYP_PIG
> 1339    3D-1.01143.01143.3SpectraST     622     595     1       1       0.71  
>   34/76
> R.LGEHNIDVLEGNEQFINAAK.IPeptideAtlas    gi|136429|sp|P00761.1|TRYP_PIG
> 1348    3D-1.01149.01149.3SpectraST     632     587     1       1       0.7   
>   36/76
> R.LGEHNIDVLEGNEQFINAAK.IPeptideAtlas    gi|136429|sp|P00761.1|TRYP_PIG
> 1400    3D-1.01180.01180.3SpectraST     697     649     2       2       0.23  
>   42/76
> R.LGEHNIKVLEGNEQFINAAK.IPeptideAtlas    gi|209572698|sp|P35030.2|
> TRY3_HUMAN
>
> and
>
> index   spectrum        hyperscore      nextscore       bscore  yscore  
> expect  ions
> peptide         protein
> 815     3D-1.00791.00791.2SpectraST     304     299     1       0       15    
>   11/18
> K.IITHPNFNGN.TPeptideAtlas      gi|136429|sp|P00761.1|TRYP_PIG
> 1472    3D-1.01223.01223.3SpectraST     569     497     1       1       0.65  
>   33/76
> K.IITHPNFNGNTLDNDIM147.04LIK.LPeptideAtlas      gi|136429|sp|P00761.1|
> TRYP_PIG
> 1490    3D-1.01234.01234.3SpectraST     559     530     1       1       4.9   
>   30/76
> K.IITHPNFNGNTLDNDIM147.04LIK.LPeptideAtlas      gi|136429|sp|P00761.1|
> TRYP_PIG
> 1545    3D-1.01268.01268.3SpectraST     585     555     1       1       4.2   
>   28/76
> K.IITHPNFNGNTLDNDIMLIK.LPeptideAtlas    gi|136429|sp|P00761.1|TRYP_PIG
> 1553    3D-1.01273.01273.3SpectraST     581     555     1       1       8.4   
>   24/76
> K.IITHPNFNGNTLDNDIMLIK.LPeptideAtlas    gi|136429|sp|P00761.1|TRYP_PIG
> 1565    3D-1.01280.01280.3SpectraST     531     522     1       2       7.5   
>   32/76
> K.IITHPNFNGNTLDNDIMLIK.LPeptideAtlas    gi|136429|sp|P00761.1|TRYP_PIG
>
> So, obviously, those peptides did not pass the PeptideProphet filter.
>
> ** Any recommendation, how to fix this to obtain a higher sequence
> coverage  in the TPP? **
>
> Note:
> If I tick the PeptideProphet Option " Force the fitting of the mixture
> model (bypass automatic mixture model checks) " I increase the
> sequence coverage of other proteins, but those trypsin fragments
> still do not show up.
>
> Thanks a lot and greetings,
>
> Robert
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