I really like this protocol because it is so very straight forward (after the sample prep...ugh...) and we took a swing at something similar a while back and had absolutely no luck whatsoever (on a different instrument platform). Here is a very clear, well written, protocol to show you how to do it.
It should be open since I don't have an affiliation right this second and I can read it.
Here is the idea, though. When you use TMTCalibrator/SCoPE-MS/iBASIL/BOOST. You generally start with a whole proteome that you label with one isobaric tag. Then you mix that with isobaric tagged extremely low level or single cell samples, right?
In Equine Clostridium perfringens (Equi-CP, and to be fair, I didn't read the part where I was supposed to learn where the name came from. You take synthetic peptides and label those with one channel, clean them up and then spike those in your labeled single cells.
Then this group just does plain old DDA on a nice previous generation Orbitrap. It goes along just doing MS1 scans until it hits your synthetic peptides, fragments those and - boom - you have single cell data. I also like how they pseudo-randomize their samples with the MANTIS and (had we seen this earlier) Dr. Colten Eberhard's spring working out how to pseudorandomize 4,000 mouse brain cells from 6 different mice might have been a little less stressful for him to sort out because they ultimately came to very similar methods. (Though Colten had a x6 matrix, not a x2 and the guy with career defining dysgraphia/dyslexia typing this post was like "omg, there is no way in this world I can help you at all" (something he clearly knew after 4 years).
Super cool, though, right? What we tried to do was take all the peptides from the RAS pathway kits from Thermo and then label those with one channel. Honestly, I still don't know if we were just way too ambitious / outside of our dynamic range or if the cells just didn't tag well in that batch. Either way, when I do it again, I'm using this protocol verbatim.
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