Molecular pixelation - single cell proteomics (of about a dozen targets) with subcellular resolution (sortof)!

 

I read this while not even Jalen Brunsen dismantling the Pacers could keep me from falling asleep (rough spring so far) but it is totally worth thinking about. 

Coincidentally, this paper prominently features another New Yorker (AOC) which is the only abbreviation I'll now ever remember for antibody oligonucleotide conjugates.

There are a whole ton of single cell technologies where you put an oligo on an antibody and you mix that with your single cells and analyze them. In our experience with these so far - THEY ARE NOWHERE NEAR AS TURNKEY AS SALESPEOPLE WHO WANT TO USE UP YOUR TIME WILL TELL YOU. If you're interested in extremely clean CD8 positive cells in culture and you want to measure the number of cells with CD8 (or whatever) there are solutions. If you want to take some tissue and homogenize it, you might give them a whole lot of money and then get calls from their apps teams asking you to give them tips and tricks because no one has ever pulled it off before. (Reasonably accurate story). 

However - ain't no one giving you spatial estimates of their "quantitative" in a very very vague and possibly inaccurate use of the word single cell proteomics data! (Very very fast, though!!) 

So this new one providing some spatial context on where the proteins ARE inside the cells? That's new to me! 

Okay - then right after I hit post on this the first time I remembered this one that I absolutely need to read! For some reason I can't post pictures right now and I don't have time to spend uploading. Gotta go go go. 

Sharing Proteomics Data While Safeguarding Individuals’ Privacy!

 

Well....at the top of the "I'd rather not talk about this one, but I know we absolutely need to have this conversation..." list! 

Unlike some of the other times this has come up in the literature where someone is like "omg, I can totally figure out who this person is from this dandruff we found!" This one suggests some well-considered solutions. 

Gary Siuzdak dropped a new book - Activity Metabolomics!

Thanks r/massspectrometry! I didn't know about this. I have Gary's Mass Spectrometry for Biotechnology which was a key part of Iulia Lazar's class on bioanalytical instrumentation when I was in grad school. 

This is on an obviously inferior -omics but I bet it's a solid read and it's like $14 in paperback! 

What are R&D instrument depreciation rates based on?

 

If you're just wondering if the guys in suits who say words like "depreciation" and "gestation lag" (and might seem like the sort of guys having fun in college while you were doing enzyme kinetic curves) are just making stuff up - they do appear to have some math to rely on here and there.

This comes from what might be the worst name of an academic journal I've ever heard of, but it's funny how much (what I can understand of it) seems to line up with reality.

That Orbitrap Velos didn't get more valuable while you were using it. It likely got less. And how long was it before you felt you really had to upgrade it to make your customers happy or to get to those low copy number proteins where all the cool stuff seems to hide? 

Carrier channel pollution - the other downside of "boosting"!

This is a thoughtful addition to the challenges with carrier channel boosting proteomics samples. The isotopic impurities are something you can largely ignore when your signal is roughly equivalent, but when it isn't, it's a big problem.

It does make you wonder if there might be a way to make expensive multiplexing tags that are...I dunno.... actually pure...? 

The explosion of "single cell proteomics" papers is not matched by single cell data!

As part of a big review we've been working on for a while, and might be a little late (sorry) we've been really digging into the data behind "single cell proteomics" studies. I really really like this review from friends in Austria because I don't know how to do these publication search term analyses and I can just steal theirs.

To people in the outside world it probably looks like we've completed hundreds - or at least....dozens.... of studies where single normalish-sized single cells were analyzed by LCMS. 

Our list does not have even 2 dozen actually studies. I'm sure that will change at some point. 

Two valuable new entries in everyone's favorite topic - quality control in proteomics!

 

Ready to get super pumped about leaving the lab and not thinking about proteomics for a few days? I'll help you get started with 

QUAAAAAALLLLIIIIIIIITTTTTYYYYYY  COOOOONNNTRRRROOOOOLL PREEEPRIINNNTTS!

Let's start with this great new Primer! 

Just like how you have to put primer on right after you sand most things and before you do the actual hard part of applying the paint people will see --- this'll get you ready for the this bit of important misery --

The definition and analysis of proteomes should be based in reality - not convenience!

 

Got a few minutes to read through a summary of 210+ references and a thoughtful perspective of what proteomics does -and doesn't - do well today? 

100% recommended! 

DecryptM - 31 cancer drugs in 13 cell lines = 1.8 MILLION dose response curves!

 

I'm re-reading this paper from last spring and - wow - 

Don't want to read? Just interested in how a bunch of relevant drugs alter the proteome, phosphoproteome, ubiquitinome or acetylome of different cell lines? 

Check out this ridiculously nice data portal here! 

Is MS Office trying to save all your stuff in some imaginary "Cloud" place?

 

I had another mandatory Microsoft update thing which 1) enabled their ....sub-performing.... blend of ChatGPT and Bing in the lower right corner of my screen where the button should be to get me back to my desktop... and 

2) Makes it so that if I open a document from my desktop and go to save it as a new name it defaults to some imaginary "cloud" thing so I will never ever be able to find it again. You can "other save options" or you can:

Open every one of the MS Office things you use 

Go to file

Go allllllllllllllllllllllllllllllllllllll the way down to Options

Go to Save and shut off this toggle that you never turned on in the first place. 

You are welcome.