Hi David

I have attached a link to the following files 
- one replicate per condition .d file (file starting with "C_" had IDs but 
no values that could be extracted for quantification)
- comet parameter file I used
- fasta file I ran the search with.

Let me know if I can share anything else!

Box_link_diagnosis 
<https://cornell.box.com/s/5y2uak2twszajaniaqpnevxn4zdneu54>
Best
Shagun

On Tuesday, August 13, 2024 at 11:05:42 AM UTC-4 David Shteynberg wrote:

> Hello Shagun,
>
> Thank you for the detailed report.  If you are able, please first compress 
> (into a zip or similar) and then share some of the problem .d files so I 
> can try to replicate this issue on my computer before I offer any 
> suggestions.  
>
> Cheers!
> -David
>
> On Tue, Aug 13, 2024 at 7:50 AM Shagun Gupta <[email protected]> wrote:
>
>> Hi all
>>
>> I have been experiencing issues processing .d files obtained from a 
>> Bruker timsTOF HT in DDA-LFQ mode, more specifically getting quantification 
>> - precursor intensity - per spectra. I am using TPP V6.3.3 Arcus on a 
>> windows computer. 
>>
>> Details
>> - There are 12 .d files (4 repeats of 3 conditions) composed of a human 
>> with yeast proteome spike in at different ratios.
>> - Converted to .mzXML using msconvert
>> - Searched with COMET and a search database taken from UniProt for Homo 
>> sapiens+Yeast
>> - Processed with PeptideProphet (filtered at probability associated with 
>> 1% FDR), XPRESS, ProteinProphet. Ran with -PREC flag (PeptideProphet), -i 
>> flag (XPRESS)
>> - Want to do hypothesis testing (comparing the three conditions pairwise) 
>> using MSstats. So require raw precursor intensity values to make a file 
>> that can be used as input to MSstats.
>>
>> Unfortunately after trying the above, and a few more things, while I get 
>> a large number of PSMs passing FDR (~30k), a large proportion of them do 
>> not have any precursor intensity value (<1k have some "light area" values). 
>> Using the "light area" values also does not give expected results (its a 
>> benchmarking dataset and processing with MSFragger gave excellent results 
>> that align with expected ratios etc.). Could you suggest things I could be 
>> doing differently to get the right results? (I imagine it might have 
>> something to do with the initial conversion to mzXML itself?) 
>>
>> Happy to share any other details needed!
>>
>> Best
>> Shagun
>>
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