Hi Carolina,

It appears the file you've sent me does contain mixture models, so I am
really not sure why you are seeing this message at all.  If you can send
the input file for both one that shows the warning and one that doesn't I
might be able to figure it out.

Cheers,
David

On Mon, Jun 19, 2017 at 9:56 AM, Carolina <
[email protected]> wrote:

> Hello David,
> I would like you to check the results if you have time. I thought it was
> weird because I have two other replicates and they are fine with high res,
> it is QE data, but again, you might be right and this sample is having some
> issue with high res. They are DDA data with three replicates, I searched
> them on Comet, and then I applied PeptideProphet. I did all of them with
> low resolution, but then I saw that I could apply high res to these
> samples, so I did. But only in one of the replicates I got that problem
> with high resolution.
>
> This is the link to the results:
> https://we.tl/RKKys1U24y
>
> This is the log:
>
> C:/TPP/bin/xinteract (TPP v5.0.0 Typhoon, Build 201610111222-7423 
> (Windows_NT-x86_64))
>  PPM mode in Accurate Mass Model ...
> running: "C:/TPP/bin/InteractParser "/tmp/a07480/params/Rep5_2.pep.xml" 
> "041117_DDA_Rep5.pep.xml" -L"7"" file 1: 041117_DDA_Rep5.pep.xml
> SUCCESS: CORRECTED data file 
> c:\TPP\data\3lib_newComet_params_0.05mzTolerance\041117_DDA_Rep5.mzXML in 
> msms_run_summary tag ...
> SUCCESS: CORRECTED data file 
> c:\TPP\data\3lib_newComet_params_0.05mzTolerance\041117_DDA_Rep5.mzXML in 
> msms_run_summary tag ...
>  processed altogether 76587 results
> INFO: Results written to file: /tmp/a07480/params/Rep5_2.pep.xml
> command completed in 12 sec
> running: "C:/TPP/bin/DatabaseParser 
> "/tmp/a07480/params/Rep5_2.pep.xml""command completed in 0 sec
> running: "C:/TPP/bin/RefreshParser "/tmp/a07480/params/Rep5_2.pep.xml" 
> "c:/TPP/data/dbase/UniProt_Human_reviewed_05-05-2016_reversed.fasta""
>   - Searching the tree...
>   - Linking duplicate entries...
>   - Printing results...
>
>   - Building Commentz-Walter keyword tree...command completed in 5 sec
> running: "C:/TPP/bin/PeptideProphetParser "/tmp/a07480/params/Rep5_2.pep.xml" 
> MINPROB=0.05 PPM"using PPM mass difference
>  (Comet)
> init with Comet trypsin
> MS Instrument info: Manufacturer: Thermo Scientific, Model: Q Exactive 
> Orbitrap, Ionization: UNKNOWN, Analyzer: UNKNOWN, Detector: UNKNOWN
>
> INFO: Processing standard MixtureModel ...
>  PeptideProphet  (TPP v5.0.0 Typhoon, Build 201610111222-7423 
> (Windows_NT-x86_64)) AKeller@ISB
>  read in 0 1+, 50647 2+, 20114 3+, 4175 4+, 597 5+, 159 6+, and 0 7+ spectra.
> Initialising statistical models ...
> Iterations: .........10.........20.........30.....WARNING: Mixture model 
> quality test failed for charge (2+).WARNING: Mixture model quality test 
> failed for charge (3+).
> model complete after 36 iterations
> command completed in 3 sec
> running: "C:/TPP/bin/ProphetModels.pl -i 
> /tmp/a07480/params/Rep5_2.pep.xml"Analyzing /tmp/a07480/params/Rep5_2.pep.xml 
> ...
> Parsing search results 
> "c:\TPP\data\3lib_newComet_params_0.05mzTolerance\041117_DDA_Rep5 (Comet)"...
>   => Found 3406 hits. (0 decoys, 0 excluded)
>   => Total so far: 3406 hits. (0 decoys, 0 excluded)
> command completed in 1 sec
> moving tempfile /tmp/a07480/params/rep5_2.pep.xml to rep5_2.pep.xml
> running: "C:/TPP/cgi-bin/PepXMLViewer.cgi -I 
> /tmp/a07480/params/rep5_2.pep.xml.a07480"command completed in 0 sec
> running: "C:/TPP/bin/tpp_models.pl "c:/TPP/data/params/Rep5_2.pep.xml""File: 
> c:/TPP/data/params/Rep5_2.pep.xml
>  - in ms run: 
> c:\TPP\data\3lib_newComet_params_0.05mzTolerance\041117_DDA_Rep5...
> -------------------------------------------------------------------------------
> TPP DASHBOARD -- started at Fri Jun 16 18:59:42 2017
> -------------------------------------------------------------------------------
> File c:/TPP/data/params/Rep5_2.pep.xml is pepxml
> Found fval (+1) model...
> Found ntt (+1) model...
> Found nmc (+1) model...
> Found massd (+1) model...
> Found fval (+2) model...
> Found ntt (+2) model...
> Found nmc (+2) model...
> Found massd (+2) model...
> Found fval (+3) model...
> Found ntt (+3) model...
> Found nmc (+3) model...
> Found massd (+3) model...
> Found fval (+4) model...
> Found ntt (+4) model...
> Found nmc (+4) model...
> Found massd (+4) model...
> Found fval (+5) model...
> Found ntt (+5) model...
> Found nmc (+5) model...
> Found massd (+5) model...
> Found fval (+6) model...
> Found ntt (+6) model...
> Found nmc (+6) model...
> Found massd (+6) model...
> Found fval (+7) model...
> Found ntt (+7) model...
> Found nmc (+7) model...
> Found massd (+7) model...
> --> Trying to write file c:/TPP/data/params/Rep5_2.pep-MODELS.html
> -------------------------------------------------------------------------------
> Finished at Fri Jun 16 18:59:43 2017 with 0 errors.
> -------------------------------------------------------------------------------
>
>
> command completed in 1 sec
> C:/TPP/bin/InteractParser "/tmp/a07480/params/Rep5_2.pep.xml" 
> "041117_DDA_Rep5.pep.xml" -L"7" 12 sec
> C:/TPP/bin/DatabaseParser "/tmp/a07480/params/Rep5_2.pep.xml"
> C:/TPP/bin/RefreshParser "/tmp/a07480/params/Rep5_2.pep.xml" 
> "c:/TPP/data/dbase/UniProt_Human_reviewed_05-05-2016_reversed.fasta" 5 sec
> C:/TPP/bin/PeptideProphetParser "/tmp/a07480/params/Rep5_2.pep.xml" 
> MINPROB=0.05 PPM 3 sec
> C:/TPP/bin/ProphetModels.pl -i /tmp/a07480/params/Rep5_2.pep.xml 1 sec
> C:/TPP/cgi-bin/PepXMLViewer.cgi -I /tmp/a07480/params/rep5_2.pep.xml.a07480 0 
> sec
> C:/TPP/bin/tpp_models.pl "c:/TPP/data/params/Rep5_2.pep.xml" 1 sec
> job completed in 22 sec
>
>
> El sábado, 17 de junio de 2017, 9:54:15 (UTC-7), David Shteynberg escribió:
>>
>> Without seeing your search results, my guess is that in your high res
>> search the filter is so stringent it excludes many of the correct results
>> you see using the low res filter in the other search.
>>
>> -David
>>
>> On Fri, Jun 16, 2017 at 7:58 PM, Carolina <[email protected]>
>> wrote:
>>
>>> Hello David,
>>> It worked perfectly. Thank you again for your help!
>>> Now I am dealing with some weird problem, I believe. I searched the same
>>> raw files on Comet with comet params for low resolution, and I did another
>>> search with params for high resolution. Both results were run with
>>> peptideprophet but in the low res one I did not get any warning, and in the
>>> High res I got warning on the mass model for charges +2 and +3, so I got a
>>> few proteins comparing with the other one. Would you know what the problem
>>> could be? Thank you so much. I am pretty new using TPP, so I am learning.
>>> Sorry for bothering.
>>> Carolina
>>>
>>> El jueves, 15 de junio de 2017, 17:05:23 (UTC-7), David Shteynberg
>>> escribió:
>>>>
>>>> Hello Carolina,
>>>>
>>>> I was able to track down the issue in the analysis.  By default,
>>>> PeptideProphet multiplies the PSM probability by the LIB probability when
>>>> processing SpectraST results.  In your particular workflow, the LIB
>>>> probability appears to be 0 for all entries, which forces all
>>>> PeptideProphet probabilities to 0 also.  To avoid this PERFECTLIB flag must
>>>> be enabled for PeptideProphet analysis of your data.  The option -OB does
>>>> this in xinteract (and also the "Analyze Peptide" Petunia page).  When
>>>> using Petunia GUI "Analyze Peptides" , add "-OB" to the Advanced
>>>> Commandline Options.  Please report back if it fails to analyze with this
>>>> option set.
>>>>
>>>> Cheers,
>>>> -David
>>>>
>>>>
>>>>
>>>> On Tue, Jun 13, 2017 at 10:52 AM, David Shteynberg <
>>>> [email protected]> wrote:
>>>>
>>>>> Having multiple decoys in your data is not a problem,  in fact it
>>>>> gives you the ability to estimate the FDR in different ways.  It appears
>>>>> that there is significant overlap between the negative and positive
>>>>> distribution models so PeptideProphet  tries to invalidate the mixture
>>>>> model.  Force fitting the distribution is usually not advisable.  You can
>>>>> try different models, for example  try turning off  "Use
>>>>> Non-parametric model".  If you are able to forward the dataset as a link 
>>>>> on
>>>>> the cloud I would be able to suggest other analysis paths.
>>>>>
>>>>> Cheers,
>>>>> David
>>>>>
>>>>> On Tue, Jun 13, 2017 at 9:47 AM, Carolina <[email protected]>
>>>>> wrote:
>>>>>
>>>>>> Hello David,
>>>>>> thank you for the answer. I have more than 2858 unique proteins, and
>>>>>> 10051 unique peptides. I think that should be enough IDs. The
>>>>>> PeptideProphet parameters were:
>>>>>>
>>>>>> Filter out results below this PeptideProphet probability:0.05
>>>>>> Minimum peptide length considered in the analysis: 6
>>>>>> Force the fitting of the mixture model (bypass automatic mixture
>>>>>> model checks)
>>>>>> Use decoy hits to pin down the negative distribution. Decoy protein
>>>>>> names begin with: DECOY
>>>>>>                  Use Non-parametric model (can only be used with
>>>>>> decoy option)
>>>>>>                  Report decoy hits with a computed probability
>>>>>> (based on the model learned).
>>>>>>
>>>>>> I also tried different combinations, with the two decoy options
>>>>>> together or not selected, but I alwasy got negative prob. The third
>>>>>> parameter I tried without it, but I got an error *Command FAILED*
>>>>>> RETURN CODE:65280
>>>>>>
>>>>>> Found 33182 Decoys, and 167398 Non-Decoys
>>>>>> Iterations: .........10.........20.....WARNING: Mixture model quality 
>>>>>> test failed for charge (1+).WARNING: Mixture model quality test failed 
>>>>>> for charge (2+).WARNING: Mixture model quality test failed for charge 
>>>>>> (3+).WARNING: Mixture model quality test failed for charge (4+).WARNING: 
>>>>>> Mixture model quality test failed for charge (5+).
>>>>>> model complete after 26 iterations
>>>>>> command completed in 114 sec
>>>>>> running: "C:/TPP/bin/ProphetModels.pl -i 
>>>>>> /tmp/a08552/Results_SpectraST_Search_3lib/interact.pep.xml -d 
>>>>>> "DECOY""Analyzing 
>>>>>> /tmp/a08552/Results_SpectraST_Search_3lib/interact.pep.xml ...
>>>>>> Parsing search results 
>>>>>> "c:/TPP/data/Results_SpectraST_Search_3lib/041117_DDA_Rep1 
>>>>>> (SpectraST)"...
>>>>>>   => Found 0 hits. (0 decoys, 0 excluded)
>>>>>>   => Total so far: 0 hits. (0 decoys, 0 excluded)
>>>>>> Parsing search results 
>>>>>> "c:/TPP/data/Results_SpectraST_Search_3lib/041117_DDA_Rep4 
>>>>>> (SpectraST)"...
>>>>>>   => Found 0 hits. (0 decoys, 0 excluded)
>>>>>>   => Total so far: 0 hits. (0 decoys, 0 excluded)
>>>>>> Parsing search results 
>>>>>> "c:/TPP/data/Results_SpectraST_Search_3lib/041117_DDA_Rep5 
>>>>>> (SpectraST)"...
>>>>>>   => Found 0 hits. (0 decoys, 0 excluded)
>>>>>>   => Total so far: 0 hits. (0 decoys, 0 excluded)
>>>>>> command completed in 0 sec
>>>>>> moving tempfile 
>>>>>> /tmp/a08552/Results_SpectraST_Search_3lib/interact.pep.xml to 
>>>>>> interact.pep.xml
>>>>>> running: "C:/TPP/cgi-bin/PepXMLViewer.cgi -I 
>>>>>> /tmp/a08552/Results_SpectraST_Search_3lib/interact.pep.xml.a08552"
>>>>>> command "C:/TPP/cgi-bin/PepXMLViewer.cgi -I 
>>>>>> /tmp/a08552/Results_SpectraST_Search_3lib/interact.pep.xml.a08552" 
>>>>>> failed: Unknown error
>>>>>>
>>>>>> command "C:/TPP/cgi-bin/PepXMLViewer.cgi -I 
>>>>>> /tmp/a08552/Results_SpectraST_Search_3lib/interact.pep.xml.a08552" 
>>>>>> exited with non-zero exit code: 255
>>>>>> QUIT - the job is incomplete
>>>>>>
>>>>>>
>>>>>> So in order to avoid that error, I needed to select the third
>>>>>> parameter.
>>>>>> Let me know what kind of problem do you think I am having. I just
>>>>>> realized, that I had DECOYs on my library, but also reverse in the 
>>>>>> database
>>>>>> fasta file. Would that be an issue? I will try to fix that and see if it
>>>>>> gets better.
>>>>>> Thanks abain for your time.
>>>>>> Carolina
>>>>>>
>>>>>> El martes, 13 de junio de 2017, 8:07:12 (UTC-7), David Shteynberg
>>>>>> escribió:
>>>>>>>
>>>>>>> Negative probabilities are output as place holders when there aren't
>>>>>>> enough IDs to estimate a valid mixture model.   When PeptideProphet 
>>>>>>> cannot
>>>>>>> compute a probability but based on other models thinks the ID is 
>>>>>>> correct it
>>>>>>> reports it with a negative probability equal to the absolute charge. It
>>>>>>> would be helpful to know your PeptideProphet parameters to help
>>>>>>> troubleshoot the failure to report a mixture model probability.
>>>>>>>
>>>>>>> -David
>>>>>>>
>>>>>>> On Mon, Jun 12, 2017 at 5:15 PM, Carolina <[email protected]
>>>>>>> > wrote:
>>>>>>>
>>>>>>>> Hello,
>>>>>>>> I built a library with decoys with SpectraST, and then, performed
>>>>>>>> the search of raw files also with SpectraST against that library. The
>>>>>>>> results were analyzed with peptide prophet but the probabilities are 
>>>>>>>> all
>>>>>>>> negative, from -2 to -7. My intention is to get a FDR on my results, 
>>>>>>>> and
>>>>>>>> that probability can not be right. Would you know what it might be 
>>>>>>>> going
>>>>>>>> on? Thanks, Carolina
>>>>>>>>
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>>>>>>>
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>>>>>
>>>>>
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