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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