Single NUCLEI proteomics (and identification of cancer mutations in single cells!)

 

I'll start with the figure above because it's early in the paper. Super exciting to me personally because of my personal research interests. These peptides are hard to identify in bulk. This group is doing them in single human cells.

How? They're building libraries for the software that we like to run library free the old fashioned way. They're capturing the specifics of their instrument as well as the unique characteristics of how peptides at super low intensity/concentration tend to behave. So this is all label free proteomics by data independent acquisition used to resolve both human mutations AND PTMs in single human cells. Wow, right? 

THEN this group broke through to the next level of what single cell proteomics (SCP) needs to do. THEY ANALYZED SINGLE NUCLEI. For context, if you look at what a large percentage of "single cell seq / scSeq" is actually analyzing, it is actually nuclei harvested from fixed tissues. The nucleus is pretty tough and it can often be separated from materials where the rest of the cell won't be recoverable.

Things like fixed tissue. And we have LOTS of that.

They only analyzed around 100 single nuclei here, but I honestly thought we'd see nuclei 5 years from now. When I first saw these results around the end of 2023, I couldn't believe it. It should be noted that we've recently saw a new preprint that did a few thousand single nuclei, so I was waaaay off in my estimates. Super super cool new paper.