Preprinted data featured at SCP2026 day 2!

Whoa. Day 1 kicked off with "you should get another espresso, Ben" this is some heavy stuff. Preprinted here, though! 

For you mass spec nerds the method is worth thinking about. What if you spiked each single cell with the same SILAC heavy bulk digest? It looks like it works really well, but what he cares about is intrinsic vs extrinsic noise in -omics datasets. 

Damn, what a cool work. They also do metabolic labeling and then single cell proteomics. And I honestly think the preprint contains every detail necessary to reproduce this method and analysis. I wouldn't even know where to start for processing SILAC diaPASEF data in DIA-NN, but - boom - they're all there! 

Oh. 

Ummmmm.......okay....so...this ISN'T preprinted yet, but I didn't beat 3 other people to basically the same question. So...maybe just watch out for an upcoming Parallel Squared preprint from Dr. Megan Elcheikhali where they succeeded in something that an extremely skilled former postdoc in my lab (and many other great scientists in other labs) have failed to do. I'm dying to know what the trick is. (Likely very very many tricks.) 

This happens to me all the time: 

Someone kicks in my office door and yells  "HEY NERD! I'm here to do single cell proteomics! I've got a bunch of brains or livers in this Yeti cooler in the trunk of my car!" And I have to say "Wait. What? Where do you get all these organs? And why did you freeze the whole thing?? If you froze it, the cell membranes definitely ruptured, so you can't sort them. And if they can't be sorted with an intact membrane, it doesn't work. 

So....if what she said is real then....about 9 out of ever 10 collaboration requests I turn down might actually be ....viable.... so.... this was a ridiculously important talk. 

Man, I really thought I was going to bug out and work on a proposal I really think is going to define the rest of my career, but - damn this panel talk was lit. 

Topics covered -

-Most biologists still don't know single cell proteomics is a thing. But the point was brought up that most biologists don't really know that proteomics is a thing. Not in the way we currently do it. 

-Slavov shared some tips for how he's finding all these amazing collaborations. Cutting out as much useless jargon as possible and engaging everyone he can in other fields. The 100 Nature family papers probably doesn't hurt. 

-Definite concerns about costs discussed by everyone. No real solution yet. 1,000 single cells from some weird cell line is still going to be expensive. 

I had to do some ...work...ugh...and I only half paid attention to the next couple of talks. 

This seems like the most recent paper out of one of them. Though you'll find these authors are prolific right now. 

I had an alarm set for Ronnie Cutler's talk and it didn't disappoint. I'm not sure what I can share from that one yet. Maybe, what if you really did look at integrating single cell transcriptomics - not the read count data, but the other data you get from it. At a single cell level. With PTMs you can target at those same levels, maybe you can find a depressing (for old people like me) story in it? 

It's after 3am when I'm posting whatever I typed in this orange box, because I did get to doing the work ...ugh... stuff I needed to. I did finally get to see a talk on how the AIP works from a guy with an amazing last name. If he was at Thermo, new people would infer that he was critically involved in the development of their long running series of flagships. And Bernard Delanghe found out that no one there wanted to look at mass spectra. I feel like there was another preprint I had in hand, but I forget. 

It was yet another amazing meeting in a long string of them. 

Preprinted data featured in Day 1 at SCP2026!

 

I've got to start a new page of notes for day 2 or OneNote will definitely crash. Obviously there is a lot of unpublished data here I don't know if I can share or not, but some of this is out or preprinted. 

If you very very carefully controlled pH and reaction kinetics could you label all of one side of a peptide with TMT and all of the other side with dimethyl labels? Apparently, yes.

Nikolai beat me to the question of "wait. better than 95% labeling efficiency ON BOTH TERMINI?"

The only link I can find to this publicly so far is a dissertation that is public (and really really well written) you can find here.

Now...the stochastic sampling appears to be a major issue because you have 3-plexes of each TMT tag. So you drop to a very low overlap from cell to cell. I'm personally about 90% sure that it's due to MIPs. That's a lot of complexity that is far outside of the model of averagine within a very tight m/z window, but it does still allow for separating very different cell types apart. They have tried semi-targeting and other intelligent acquisitions, but - this ain't a terrible start for huge throughput potential. Especially if they've worked out the double labeling kinetics so you and I don't have to. 

And there are always people at this meeting doing crazy stuff out there you never heard of, right? Like, where does Parallel Squared find these people? This was the first one of the meeting and it was preprinted a few months ago. 

Crazy and amazingly ambitious. So...what if you coupled expansion microscopy (where you put the diaper gel stuff on your tissue and stretch it out so you can image it? But you did that to de-crowd the spatial peptide domain enough that you could essentially do Edman single molecule degradation in a spatial context? You might immediately have objections about depth, complexity, and orders of magnitude or 6 that would be tough to reach, but - damn....I would have never ever thought of this, nor have I ever heard anything even remotely similar to this idea. Really really cool. 

One more. I don't understand this one, but it's another off-the-wall technology and I really liked the speaker and his animations for BALLISTIC MICROSCOPY!

MORE EMERIL! 

Day 2 is starting now! Let's go! 

It's finally here! SCP2026!

 

The world's first conference on Single Cell Proteomics is back - today! for it's 9th year. That doesn't seem possible, but I counted twice. 

I can't wait. The line up is amazing. Is it too late to register digitally? Probably! But you should have already, silly. If you do miss it, most of the talks every year end up curated and up on YouTube! I watch the old ones on my lunch breaks all the time. 

Got a backup tablet in my bag for notes if my primary's battery can't survive me writing for 10 hours!

It looks like an absolute ton of speakers today because of the 5 minute flash talks in the middle of the day. The schedule doesn't fit on a single screen? Well, I'll screenshot it so it feature the talk I'm most excited for at 4:45! 😮

It's official! THE Proteomics Show live at the British Mass Spec Society!

 

A couple days ago I found out about the iSCMS BMSS joint meeting in London in October. 

I was like "who is organizing this and how can I help?" 

So now I am! If you are at BMSS, you can put your name into a literal hat. Hopefully a fancy London hat! And get interviewed in front of a live audience for an episode of THE Proteomics Show.

Is it cold enough in October there for me to dress up like Tom Baker the whole time? Or will I be sweaty and itchy the whole time? Or both? You'll have to be at the BMSS meeting (October 9th!) to find out. 

New spatial mass spectrometry technology alert - Tippy Tapping-Mode ESI!

Are you interested in getting into spatial mass spectrometry but all the super expensive commercial technologies aren't doing it for you? 

Why don't you...

..introducing Tappy-mode scanning ESI! 

What's that? Okay, they didn't invent it for this paper, but they explain it better than I can! 

Wait a minute. Is it just like this except really fast and with an electrospray plume in the middle? 

Close enough! 

Okay, but analogies aside, we can move tissues at incredibly absurdly high resolutions. Think about the stages they use for electron microscopy! Great imaging mass spec today is like 20 micron. Every vendor will sell you a "5 micron resolution"capable device, but have you ever seen a mass spec imaging ..image...at 5 micron without inflating it with diaper gel? I sure haven't. But EM stages can move in like sub micron easy. The limitations are things like our laser pixels. And when you start talking to people who do anything with piezos (which more the bird beak or capillary), those people are talking about things running at 10-100 kHz (10,000 to 100,000 vibrations/second!)  So...I'm totally talking out my nose, but these authors say they're doing 10 and 5 micron and while a healthy truckload of skepticism is always a good idea, this doesn't sound all that far fetched.....

They couple the device to a Waters TOF and then use multiple commercial software solutions from Waters and Shimadzu to convert and extract the data before going to LipidMaps to match the molecules they extracted. (They did lipids for this, I was leaving that part for the end) but why couldn't you pick up a little piezo capillary worth of intact proteins or digested peptides and do the exact same thing? Cool idea, right? 

iSCMS is in London October 6-8 plus an extra day for BMSS October 9!

 

iSCMS 2026 was just announced and it's SO cool. 

One of my favorite 2 day conferences - not just single cell proteomics, but all single cell mass spectrometry. At King's College in London! 

And if that's not cool enough it's a joint conference. You can stay an extra day for the British Mass Spectrometry Society Meeting! Alejandro Brenes and Felicia Green are the plenaries for the latter! 

Did you think that you had to be 90 years old to be a plenary speaker? Not here you don't! Psyched for both talks. 

You can come for BMSS or iSCMS or both and register here. 

Here are some completely and totally unrelated facts about that same week in London that are, in no way, affecting my personal travel plans because I'm a grown up professional. 

However, THE HAUNTED are playing October 8th. I've never seen them live, but I'd clearly be responsibly in my hotel that night and preparing for BMSS the next day. Not navigating the tubes with ringing in my ears. 

I probably can't find a way to justify staying extra days, unless - I dunno - someone out there invites me to speak at their university or come by their company headquarters to talk about cool stuff. However, if you happen to be there and have flexibility -

Metal Gods - 

Amon Amarth

Soilwork 

with ORBIT CULTURE??? 

play an early show on Saturday (!?!?! WHAT !?!?!) I have no idea what a pound is in real money but 62 of anything seems like a bargain to see those 3 shows. 

Boost ultra super low input proteomics with 2 micron nanoLC columns....?

 

...ummm....how do you make a 2 um inner diameter LC column....? 

 Leaving it here so I can think about it later.

Obviously required addition to this post...

Single cell proteomics by SDS-PAGE!

 

Okay, so what if you did proteomics on a sample and you were concerned that you'd homogenized too much tissue. Maybe you had an obvious phenotype and you just can't see anything differential in the proteome? And maybe you don't have a single cell sorter in your lab and a very very clean Astral, Exploris, Excedrin, 8600 or TIMSTOF sitting around. (For real, yo, I don't think we're past the requirements for very clean or almost dedicated instruments for single cells. This is from feedback from friends with Asstrals and 3 separate Ultra2s. Run 2 days of 50ng samples and that next 50 picogram single cell is garbage. Did I just come up with a smart community study idea right now? I think I did.)

Could you, with the help of a sorting core or with some quick dilution math, and some stuff you've definitely got sitting around, find out if you have single cell heterogeneity? 

Cue the skepticism, but I think this is absolutely worth trying. Good thing I've got a lab meeting in a couple of hours! 

They straight up do SDS-PAGE with single cells! The dye is something weird, and they're clearly doing some serious magnification on their gels, but its 1) A commercial gel and 2) It's the same ol' gel dock that you've got sitting around. There was a box in my lab bay with like 10 of them and the name of a professor who retired a while back! 

Here is the workflow in my mind, though. 

1) DIA proteomics

2) ...ummm....volcano plot with like nothing in it?? 

3) Repeat with DDA proteomics

4) Process with MetaMorpheus (or Bolt if you have that $20 a file) MSFragger open search would work if you have an Orbitrap or Astral probably. FDR shuts off if you have anything else. It still seems to work but not as well. 

5) ....ummmm....even with PTMs the proteomes look the same? 

6) Dilute cells (with membranes) down to statistically 1 cell per PCR tube (or have the FACs core do some sorting for you?) 

7) SDS-PAGE a bunch! 

8) Do you have clusters like this? 

9) You've got an over-homogenization issue! See if you can do some cell sorting and do single cell TYPE proteomics (cell sorted populations) OR

 10) Bite the bullet, clean the shit out of one of your instruments. Especially if you like literally study feces. Or talk to someone who does SCP through a core or collaboration. We do single cells at Pitt for like $50 internal for 40SPD. It's more unsubsidized, but we're trying to get that $ down with more hardware.

Convert protein sequences into text and use language models to reveal all their secrets!

 

Wow. I'm completely blown away by this one. If you've got VERY GOOD AD BLOCKERS INSTALLED, you can find the popsci article here. Don't click it if you don't. Hot dog, the little counter on the corner of my screen rang up 74 ads and trackers in just a second. And the banner at the top warned me of "consequences" of blocking those 74 ads. 

The article is sort of about this new PNAS paper! Click this instead. My school doesn't subscribe to PNAS? Weird. Maybe my ad blockers are too good. 

Okay, but here is the thing. What if you could convert protein sequences to text? For real, hear me out here. You could, in theory, assign each amino acid IN ORDER an alphabetical letter. Then you could take all the complexity of a protein sequences - even one with hundreds of amino acids! - and make it just a short paragraph! 

See where I'm going with this? I bet some of you super saavy scientists do. Good for you! Then you could use that text input into - you guessed it - these amazing LLM things! 

I suspect this group at the NIH did a far better job than me when I just tried it with the LLMs I have access to, but I swear I think I just found an interesting pattern in my proteomics data with a similar approach. I have this output I haven't ever seen before. 

Serine-Histidine-(Leucine, or Isoleucine, but likely the latter)-Threonine-Threonine-Tyrosine-Serine-Histidine-(Leucine, or Isoleucine, but likely the latter)-Threonine-Threonine-Tyrosine-Serine-Histidine-(Leucine, or Isoleucine, but likely the latter)-Threonine-Serine-Histidine-(Leucine, or Isoleucine, but likely the latter)-Threonine

Have I discovered an entirely new and obviously important protein motif? It seems worth investigating for potential phosphorylation sites alone! 

MSCards - An educational game to learn mass spectrometry hardware!

 

This is so clever! And I absolutely want a deck! (In English, probably, but I'd take the French ones for sure!)

If there is an opportunity missed in this EXCELLENT paper...

 (For real, this is such a great read from authors who understand both mass spectrometry and educational concepts. Neurons from my long ago training to be a teacher stood up and tried to do things when I read words like "pedagogy"). 

...I would have ABSOLUTELY, WITHOUT A DOUBT, cited a paper by Kenneth J. Rodgers first. 

It's a preprint, there is still time! Maybe this one?