Sarah,

This is Henry Lam -- the original developer of SpectraST. I just replied to 
David about his problem and I assume you can also see the reply.

But in a nutshell, you need to keep supplying the -M <spectrast.usernmods 
file> every time you work with the library, including when you try to apply 
the quality filter, view the library, or search it.  SpectraST does not 
internalize the user-defined modifications (for a good reason, I believe), 
so it forgets them after your initial command. 

Henry

On Tuesday, December 15, 2015 at 6:05:53 PM UTC+8, Sarah P. wrote:
>
> Hi David,
>
> I'm not able to solve your problem, but I can comfort you, you are not the 
> only one with these kind of problems. Some months ago, I had similar 
> problems and until today, I could not really solve them. But in the 
> meantime, I tried a lot of different things. First, I tried to figure out 
> where exactly my problem is located. And in some points, it seems to be 
> similar to yours. So, this is what I did:
>
> I'm also working with a user defined modification. Searches with comet are 
> successful, just as in your case. In my case, however, the next step was 
> kind of a quality control as to the respective modification. So I performed 
> the TPP workflow to get an interact.ipro.pep.xml. Afterwards, I used the 
> PepXML Viewer to check on the spectral quality of the modified peptides and 
> to check whether the TPP assigns the same spectrum to the same modified 
> sequence than other search engines (comparison of original spectra out of 
> raw files). So far, it works. 
>
> Just like you, I tried to build the spectral library afterwards by 
> implementing the modification with the user defined modification file you 
> described. My file spectrast.usermods looks just like yours, only with a 
> different mass and a different amino acid residue. When I build the 
> spectral library with the command line of my computer, I also get a 
> confirmation of a successful building process. But then, I have problems to 
> work with the library. Normally, I filter the spectral library for 
> probability and then review the consensus spectra of the modified peptides 
> in my spectral library. But in this case, when I build a consensus library 
> with only high probability spectra, there are no modified peptides anymore, 
> so I cannot perform any searches of data against the library. So I removed 
> the probability filter and build up a library. But when I try to evaluate 
> this spectral library to check on the quality of the modified spectra, to 
> look at the spectra itself or to check whether the modification is set up 
> correctly, I have some problems:
>
> ·         The same spectra I could look at on the level of ipro.pep.xml 
> (high probability, correct sequence, correct modification) cannot be found 
> in the splib anymore.
>
> ·         In other cases, I find the same spectra now with very low 
> probabilities. 
>
> ·         In a third case, the same spectrum is now displayed as a 
> spectrum containing another phosphorylation or another sequence (comparison 
> of scan numbers). 
>
> ·         Most of my reference spectra will be eliminated as soon as I 
> filter the spectral library for high probability. 
>
> ·         Just in case I ignore the differences between PepXML Viewer and 
> Lorikeet Spectrum Viewer and I look at the peptides displayed in the table 
> of the splib.html, there are some differences between the table and the 
> spectrum I see when I click at the peptide in the table. For example, in 
> your case, in the table, I see the sequence DLK[324]DYFTK. When I click on 
> the spectrum, it will be displayed with the sequence DLK and without the 
> modification.
>
> ·         To be more precise, the corresponding fragment ion series can’t 
> be matched or assigned as they don’t belong to the  sequence displayed 
> either in the table or next to the spectrum of the Lorikeet Spectrum 
> Viewer. The precursor mass of the spectrum, however, belongs to the 
> sequence of the splib.html-table. The fragment masses, interestingly, are 
> sometimes even higher than the corresponding precursor masses. 
>
> ·         My next step will be to find out to which sequence the 
> displayed fragment ion series could belong, but even if I can figure this 
> out, I don’t know how this could help. 
>
> ·         Additionally, when I compare just the raw spectrum (the 
> spectrum with the same scan number than the spectrum the library took for 
> the display. I extracted the necessary information directly out of the xml 
> files.) with the results of other programs, the other softwares will find 
> another sequence belonging to this raw spectrum. I did not work with a 
> consensus library when comparing different softwares of course.
>
> ·         To complete the view, I just searched for any modified peptides 
> of the interact.ipro.pep.xml in the spectra of the splib.html, but I found 
> none. I clicked at every single Lib-ID that corresponds to a modified 
> peptide and the problem is always the same.
>
> I repeated these tests with different data sets, different versions of the 
> TPP and of spectrast, different formats of spectrast.usermods, different 
> locations of the TPP (server based and local) and also different user 
> defined modifications. The problem is always the same. 
>
>  
>
> So, I’m sorry that I cannot really help you, but maybe I can guess that 
> there is no problem with your data set or the way you perform your search 
> against the library, but only with the user defined modification in the 
> spectral library.
>
>  
>
> Is there anyone else out there having similar problems or maybe already a 
> solution for it?
>
>  
>
> Thanks in advance!
> ...

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