Hi Mark,
Skyline only needs you to manually enter a definition for your modifications once. If Skyline is not recognizing them, then that means that they are not defined in Unimod, or defined more recently than our last update. Do you feel they are represented in Unimod?
How extensively do you generate new novel PTMs?
The benefit to having you fully defining a PTM is that this operation usually involves supplying a chemical formula for the PTM, where the best we could hope to do from most search engine output is a numeric delta-mass. Numeric detlas negatively impact the ability to generate accurate isotope distributions, and more generally, Skyline no longer knows the full atomic composition of the molecules being targeted.
So, while we could add a work-around to automatically generate mass-only PTMs from most spectral libraries, we would need convincing of its necessity for an important workflow. Currently our expectation is that there should be relatively few modifications no in Unimod, and users that it is not a great burden for users to fully define the ones they want to use.
If you still feel this is not the case with you, please explain further. Maybe provide the modifications and explain why they would define a large enough space to warrant automating mass-only modifications without chemical formulas. Alternatively, we can explain to you how to create a document with extensive PTM definitions which you can share across Skyline instances, which has worked for other applications as extensive as glycopeptide modifications.
Thanks for posting your case to the Skyline support board.
--Brendan