Yes! I have also wondered this exact same question. DIA is great for protein level quan but you get lots more peptides/protein, so it works out if they aren't always as high quality as DDA proteomics.
Protein post-translational modifications still don't work as well in my hands with DIA vs DDA. My last check of human samples ran on a TIMSTOF with DDA vs DIA was like 8x more PTMs with DDA. Come on IRB paperwork! I'd love to write this paper someday.
What about those annoying single amino acid variants that every human being has? Except for the completely normal in every way Craig Venter who loaned so much early DNA that he's probably just the UniProt human database (there are many inaccuracies in this last sentence).
Don't do it yourself - read this cool open access paper!
Probably worth mentioning that this is Orbi-Orbi DDA and DIA. An Eclipse and Exploris were both employed at different points. You could probably assume some variation when you go to faster instruments with lower relative resolution/mass accuracy. So...maybe doing this analysis with a TOF might make sense?
A minor criticism is that the authors did more work than strictly necessary. You could just ignore COSMIC entirely and just go download the XMAn fasta libraries that an amazing professor (who mentored an enthusiastic weirdo a few years ago - crap, maybe it was more than a few years ago) updates every few years. Original paper here. If you wanted single amino acid variants since the 2020 (?) update, I can see doing the extra work yourself, I guess.
As an aside (surprise -enthusiasm! - maybe it's back for good?) we struggled a lot at first with my postdoc's CKB type knockout mice when doing DIA proteomics. There are lots of CKs and they are very similar. We'd see CKM(uscle) in places in mice where there is no muscle and the knockout mice were always down-regulated, not knocked out, because one peptide would be attributed to the wrong CK (creatine kinase). That seemed to get a lot better every time we'd get a new DIA-NN or SpectroNaut update.
What tool would you use for a fasta with a bunch of SAAVs in it? The paper is open access, check it out yourself. Worth noting, DIA-NN's new update specificaly has words about improving proteoform level quan in the new release notes.
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