Wednesday, April 26, 2017
Screening protein isoforms predictive for cancer with Immuno-PRM!
I saw some of my favorite talks ever today. Seriously, proteomics is going in some amazing directions. As I'm scouring through the literature to determine what I saw that has and hasn't been published from yesterday's great speakers -- I realize I've got a lot of stuff I can't talk about quite yet, but that's okay! Plenty of stuff I can!
Check this out (it's from 2015!)
It is no secret that they are translating some amazing proteomics directly into the clinic in Luxembourg. Yeoun Jin Kim contributed to an awful lot of this work and is just getting set up here in Maryland and bringing these (and new!) techniques to our community.
In this study, the Domon lab demonstrates the application of fast capture immunoaffinity with ultrafast gradients and parallel reaction monitoring. Check out those RAS peaks at the top of the page!
They use a technology called MSIA that you can read more about here --
--essentially, an automated system rapidly enriches for the protein(s) of interest.
Personally, I'd like to think that I can detect anything in a 1D separation -- but if you are under pressure to do a very rapid assay from a machine time perspective, these authors argue that rapid automated enrichment coupled with rapid LC is the way to go.
They use heavy labeled peptide standards for the main cancer driver mutations -- optimize for them in cell lines that express them -- but then show that they can find them in 4uL of plasma from real patients.
Classically, we think of QQQ and MRM in the clinics -- but they are looking for single peptide (amino acid, in some cases) changes. There aren't multiple peptides that you can use -- heck, there aren't multiple transitions you can use at unit resolution for all of these. PRM to the rescue!!