Hi Erik,
Does this mean that they are not in Unimod? The vast majority of peptide modifications in Skyline come from Unimod. Note that when you add a modification there is a dropdown list that allows you to choose from a list of named modifications. At the top of the list there is an element that will read <Show all...> (or <Show common...> when all are being shown). This allows you to toggle between the most common set of modifications and all modifications in Unimod (thanks to the Matrix Science guys for setting this bar).

If they are in fact not in Unimod, we could still add them to this list, if you can point us to a resource where they are defined. This would still require adding them one at a time, but maybe that would not be so terrible if you are just choosing from a list. Or is this what you are complaining about?

If you are savvy enough to have some understanding of XML and you just want to have a text way to define any number of modifications and import them into Skyline, then look no further than the .sky file itself. Every time you open a .sky file, Skyline adds all of its defined modifications to its list. So, you just need to add your desired modifications to the XML of a .sky file (in the correct format) and then open the file once. You can start by saving an empty Skyline document with a few modifications you would like to emulate. Then open the .sky file with your favorite text editor, even Notepad. The modifications sections are near the top of the document, and should appear in the first page of text you see.

      <peptide_modifications max_variable_mods="3" max_neutral_losses="1">
        <static_modifications>
          <static_modification name="Carbamidomethyl Cysteine" aminoacid="C" formula="C2H3ON" />
          <static_modification name="Oxidation (M)" aminoacid="M" variable="true" formula="O" unimod_id="35" short_name="Oxi">
            <potential_loss formula="H4COS" massdiff_monoisotopic="63.998285" massdiff_average="64.10701" />
          </static_modification>
        </static_modifications>
        <heavy_modifications />
      </peptide_modifications>

Even this may be enough to get you going, as the Unimod definition of "Oxidation (M)" includes a potential loss. Just copy an instance of <static_modification ...>...</static_modification>, paste, and fill out the details to meet your needs.

Hope this is helpful to you. Thanks for posting to the Skyline support board.

--Brendan

Hi Brendan,
Thanks for your suggestions.
The Unimod modifications include a few simple sugar trees, however not the more complex ones found on human plasma proteins.
Also the ones that are already in unimod have no neutral loss defined. Per sugar you can have typically 2-6 types of different neutral loss masses.

Indeed an option is to try to generate a *.sky file with all the modifications and all their neutral losses.

In bionic it nicely annotates the fragment ions with different neutral losses, see attachment. It would be great if something like this could be possible in Skyline. I used the mzidenml file from bionic to generate the skyline library.

--Erik

Usefull link to glycan mods and neutral losses:
http://www.ionsource.com/Card/carbo/carbstr.htm
http://www.ionsource.com/Card/carbo/slmmarker.htm

Thanks for the Info, Erik. We'll have a look. Without changes to Skyline, though, it sounds like creating that .sky file will be your best option. Skyline will annotate the spectrum with losses (though, only showing -delta instead of a loss name) if you get the modifications correctly added to your document.

Sounds like a great thing for us to try to make easier, though. Also, we understand that sometimes these result in charged losses, which also show up in the MS/MS spectrum, and it is already on our list to annotate these as well.

Thanks for the feedback and pointers to extra information. Good luck with achieving what you need in the current version of Skyline. Hope that works out. If so, maybe you could post back the XML snippet you use to this support request.

--Brendan