Use a carrier channel - to reduce(!?!) your boring background!

 

This smart new technical note does something that I think many people have thought about, but both pulls it off AND methodically dissects it so it's now a completely valid tool to put in our utility belts. 

Problem: There are 10,000 proteins here and I don't care about any of them. I care about the stuff after those first 10k. 

Traditional solution: Fractionate and fractionate some more and cross your fingers. 

New idea - Isobaric tag (TMT is one solution) all your peptides. Then tag (with a different channel) a higher abundance amount of the peptides that you care about.

Perfect application? Infected cells! Even if you've got a super duper bad bacterial infection pretty close to 100% of the protein around is going to be human. But if you label bacterial proteins and spike those in at a higher level you've biased your stochastic sampling toward the bacterial proteins and effectively reduced the host background! 

Where this shines is the pressure testing. Smart standards are made and tested and tested. Instruments that can reduce coisolation with tricks like MS3 seem to be the best. Ion mobility (here FAIMS) coupled MS2 comes in second and MS2 alone has a lot of background, but still works. 

The proof is divided between a bunch of public repositories. Easier to copy paste than link them here.