Selection of transitions that diminish precursor dotp

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Selection of transitions that diminish precursor dotp dkueltz  2022-01-14
 

Hi Nick, Brendan,
I was wondering if there is an automated way for identifying transitions that are interfering with the expected fragment (product) ion intensity pattern and do not conform to the pattern represented in the corresponding library spectrum. Sometimes there is a transitions that greatly "derails" the precursor dotp and when I delete those "interferences" then the dotp value increases greatly, sometimes from 0.5 or so to 0.99 if the interfering transition is high intensity in the samples but very low in library spectra or vice versa. Is there any way to automatically identify those "interfering" transitions in the document view grid? It would be nice to select them all in that grid and then delete them at once rather than having to manually check and delete them 1 by 1 for each precursor.
Thanks,
Dietmar
BTW: thanks for fixing the array dimension error in the latest Skyline daily release - much appreciated!

 
 
Nick Shulman responded:  2022-01-14
Skyline does not really do anything like that, but we have plans to add some of those features in the future.

Another tool which some of the people in the MacCoss lab use is EncyclopeDIA:
https://bitbucket.org/searleb/encyclopedia/wiki/Home

EncyclopeDIA extracts chromatograms from datasets, and decides which transitions have interference based on whether they have the same shape as the other transitions in the same precursor, and whether the transitions have consistent behavior across the replicates.
If you do use EncyclopeDIA to create a .elib file, you can get it into Skyline by doing "File > Import > Peptide Search" and choose "Use Existing".

There is also the external tool "AvantGardeDIA" which I believe is supposed to also detect interference in transitions:
https://www.nature.com/articles/s41592-020-00986-4

-- Nick
 
dkueltz responded:  2022-01-17
Thanks Nick! I am glad that this is a feature, which is on your radar for future releases of Skyline.
I tried encyclopeDIA and it works great. It filters about half of all the transitions (comparing elibs that only have quant versus all transitions included).
The blib export from encyclopeDIA has some issues - these blibs can be loaded in Skyline but for some reason when using these blibs then peak boundaries are not generated in Skyline after loading samples. So I am using the elibs instead following the import scheme you had recommended.
I tried AvantGardeDIA before but never got it to work. Now when I click on the external tools link for it, the link is broken.
Dietmar