Hi David,

Many thanks for your explanation - it's now clear to me what's going on.

Cheers,
Alastair

Am Freitag, 6. März 2020 16:40:25 UTC+1 schrieb David Shteynberg:
>
> Hello Alastair,
>
> When you ran PeptideProphet as follows:
>
> PeptideProphetParser H1_EhN_cm2.pep.xml RT DECOY=XXX_ NONPARAM 
>
> Here is what happened:
>
> You gave PeptideProphet the names of your decoys but without the flag 
> DECOYPROBS the decoy hits are all incorrect as far as PeptideProphet is 
> concerned and they will all get a probability of 0 (unless you enable 
> DECOYPROBS).
>
> By default PeptideProphet removes any results with probability less than 
> 5% unless you set the flag MINPROB=0 (or the flag ZERO).  So unless you 
> apply the flag DECOYPROBS you will not see decoys with non-zero 
> probabilities.  And if you use the flag MINPROB=0  but without DECOYPROBS, 
> all your decoys will be reported with probability 0, which will not be 
> helpful if you want to utilize these decoys later.  
>
> If you want to use these decoys later you have to rerun the analysis with 
> DECOYPROBS, and possibly with MINPROB=0 so you can count the number of 
> decoy hits at low probabilities to get the decoy rate among random matches, 
> which you can compare to the decoy rate in you database (they should be 
> similar.)  
>
> By the way, in my testing I did not find that specifying the same set of 
> decoys for the iProphet classifier is helpful, when you use iProphet after 
> PeptideProphet and PeptideProphet already utilized the same decoys.  When 
> the information about the decoys is already used at the PeptideProphet step 
> it doesn't seem to help the classification at the iProphet step.  They 
> could still be useful as a second measure of FDR, however when the 
> PeptideProphet DECOYPROBS flag is enabled.
>
> Hopefully this helps you understand the issue.  
>
> Cheer,
> -David
>
>
>
> On Fri, Mar 6, 2020 at 5:40 AM 'Alastair Skeffington' via spctools-discuss 
> <[email protected] <javascript:>> wrote:
>
>> Hello,
>>
>> I'm combining some Mascot and comet search results with TPP and have the 
>> problem that it doesn't seem to be identifying decoys correctly.
>>
>> I'm running TPP.5.1.0 on ubuntu 16.
>>
>> The comet and the mascot search are done with decoy search turned off, 
>> but I added decoys to the database with the prefix "XXX_"
>>
>> Then I continue to run TPP like this:
>>
>> InteractParser H1_EhN_cm2.pep.xml H1_ma_EhN.pep.xml H1_co_EhN2.pep.xml  
>> -D../../Databases/EhuxAllproteins_MCC_decoy.fasta -s -XH1 -Etrypsin
>>
>> DatabaseParser H1_EhN_cm2.pep.xml
>>     
>> RefreshParser H1_EhN_cm2.pep.xml 
>> ../../Databases/EhuxAllproteins_MCC_decoy.fasta
>>     
>> PeptideProphetParser H1_EhN_cm2.pep.xml RT DECOY=XXX_ NONPARAM
>>     
>> ProphetModels.pl -i H1_EhN_cm2.pep.xml
>>     
>> tpp_models.pl H1_EhN_cm2.pep.xml
>>
>> And get the following printed to stdout:
>>
>>
>> ../../../../Databases/EhuxAllproteins_MCC_decoy.fasta,../../Databases/EhuxAllproteins_MCC_decoy.fasta
>>   - Building Commentz-Walter keyword tree...
>>   - Searching the tree...
>>   - Linking duplicate entries...
>>   - Printing results...
>>
>> using RT
>> Using Decoy Label "XXX_".
>> Using non-parametric distributions
>>  (MASCOT)
>> error: -1.0 ion score
>> Analyzing H1_EhN_cm2.pep.xml ...
>> Parsing search results "/home/
>> mpimp-golm.mpg.de/skeffington/winhome/proteomics2/CAP/CAPdata/mascot/Ehnew/H1
>>  
>> (MASCOT)"...
>>   => Found 23168 hits. (0 decoys, 0 excluded)
>>   => Total so far: 23168 hits. (0 decoys, 0 excluded)
>> Parsing search results "/home/
>> mpimp-golm.mpg.de/skeffington/winhome/proteomics2/CAP/CAPdata/H1 
>> (Comet)"...
>>   => Found 21343 hits. (0 decoys, 0 excluded)
>>   => Total so far: 44511 hits. (0 decoys, 0 excluded)
>> File: H1_EhN_cm2.pep.xml
>>  - in ms run: /home/
>> mpimp-golm.mpg.de/skeffington/winhome/proteomics2/CAP/CAPdata/mascot/Ehnew/H1.
>> ..
>>  - in ms run: /home/
>> mpimp-golm.mpg.de/skeffington/winhome/proteomics2/CAP/CAPdata/H1...
>>
>> -------------------------------------------------------------------------------
>> TPP DASHBOARD -- started at Fri Mar  6 14:18:51 2020
>>
>> -------------------------------------------------------------------------------
>> File H1_EhN_cm2.pep.xml is pepxml
>> --> Trying to write file H1_EhN_cm2.pep-MODELS.html
>>
>> -------------------------------------------------------------------------------
>> Finished at Fri Mar  6 14:18:54 2020 with 0 errors.
>>
>> -------------------------------------------------------------------------------
>>
>>
>> So I don't understand why it doesn't find the decoys when they are 
>> clearly there in the search results, when they are clearly there in the 
>> .pep.xml file:
>>
>> <spectrum_query spectrum="H1.27890.27890.4" start_scan="27890" 
>> end_scan="27890" precursor_neutral_mass="1899.7835" assumed_charge="4" 
>> index="13563" experiment_label="H1">
>> <search_result>
>> <search_hit hit_rank="1" peptide="SWHGEAASKTVDSLPR" peptide_prev_aa="R" 
>> peptide_next_aa="F" protein="XXX_44165" num_tot_proteins="1" 
>> num_matched_ions="6" tot_num_ions="60" calc_neutral_pep_mass="1899.7996" 
>> massdiff="-0.0160" num_tol_term="2" num_missed_cleavages="1" 
>> is_rejected="0">
>> <modification_info modified_peptide="S[167]WHGEAASKTVDS[167]LPR">
>> <mod_aminoacid_mass position="1" mass="166.998359"/>
>> <mod_aminoacid_mass position="13" mass="166.998359"/>
>> </modification_info>
>> <search_score name="ionscore" value="15.77"/>
>> <search_score name="identityscore" value="33.71"/>
>> <search_score name="star" value="0"/>
>> <search_score name="homologyscore" value="27.00"/>
>> <search_score name="expect" value="3.1107"/>
>> </search_hit>
>> </search_result>
>> </spectrum_query>
>>
>> Any ideas would be much appreciated!
>>
>>
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>>
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