At some point you've got to step back away from the unidentified spectra problem and just let go. It will seriously drive you crazy if you don't.
Do we just have a fundamental misunderstanding of how biology works? Seriously!?!? What is all this stuff?!!?!?!?
Take into account individual genetic varation, partial cleavage events, protein dynamics, non-stoichiometric post-translational modificiations -- and you know what? You still have a buttload of spectra that sure as heck match the averagine isotope model -- but I have NO idea what they are.
Want to feel better about it? Check out this paper from Johannes Griss et al.,!
In this study, this group of smart people suggest that we can take a deep breath and distance ourselves from this problem a little -- we have these huge databases like PRIDE. What if we just look for patterns for these unidentified spectra?
Right!??!
"Hey, I don't know what these 4,000 spectra are but they pop up every time y'all do a study of cancer cells that are Her2 positive" (!!!!!)
YES. LETS. USE. THIS. INFORMATION. SOMEHOW!!
PRIDE has been proposing work like this for a while, but I honestly wasn't as excited by the original PRIDE Cluster paper or web interface, cause either I wasn't so frustrated by unmatched spectra...or it never occurred to me that this was a way to use it.
Okay. I want to use this somehow. Gotta think up a strategy.
Wait...MGF? OH. Okay. This needs more time than I have this morning. GO TO WORK, BEN!
Seriously smart paper though. One of those -- "Man, I totally should have thought about that one!" Glad there are professional proteomics people out there!
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