Thursday, August 15, 2019
THE DREAM OF SINGLE CELL PROTEOMICS!!
THIS IS REAL LIFE. Single cell proteomics is totally a thing.
Is there room to improve? Absolutely. But there is this tipping point you need to get to. If you've just got a couple of ambitious labs working on something in relative isolation they're only going to get so far, regardless of how brilliant they are. When everyone is looking at it? When there are meetings all around the world on a new topic? When Nature Methods runs a review on it? When said review points out the dominant technology (mRNA for single cell) has serious serious serious --
--- WHAT?!?! You can dissect this one all day.
3 years ago a big school near my home went crazy and spent almost $4M on proteomics technologies. In one year!! It was really exciting to be in town. At that same school, one professor spent $20M on RNA-Seq instruments and reagents. One lab. A big lab, but still. We play 4th seat cello to these "next gen" technologies year after year after year.
And -- to see something like this -- of course mRNA abundance and true protein abundance don't line up! These vaunted technologies are only getting 3 transcript measurements per gene across a cell? Which only barely puts them in the 4th order of dynamic range for genetic measurements? What?!?When the true protein measurements go orders beyond that? My take-away is that the post-transcriptional regulation machinery is massively more important to the protein regulation than the raw transcript abundance. There simply aren't enough mRNA molecules present to be otherwise. And -- even if there were and this is a technological limitation, like they actually are there, but the tech can't see them -- there isn't enough coverage from the transcript measurement data to interpret it. Either way -- direct measurement of protein should be where resources are focused! (duh.)
There is a lot more here -- including single cell SWATH (ummm....which hopefully has some ion accumulation of amplification thing cause TOFs are nowhere near sensitive enough for single cell without it) and they talk about mass cytometry and a couple of new technologies I've never heard of.