Monday, June 8, 2026

Ultra-high speed high resolution LCMS shows we're still underestimating proteomic complexity!



Wow, there are so many great ASMS week preprints, I can't even read all the ones from Jenny van Eyk's lab. This one, however, needs to jump the queue, just a little.


The topic of the paper is well detailed in the title. It's a comparison of Asstral DDA vs DIA. There are some gems in it, including the statement "DDA isn't dead yet". But what is really really super interesting is the relatively low degree in overlap when they run the same samples with DIA, small window DIA and DDA methods. Which leads the authors to type out this really really cool paragraph. 


Okay...so why do I love this so much? Let's go back in time 12 years or something to this paper I ranted about a second or third time here

In 2014 or so, these authors used an Orbitrap Elite and ran some long (by today's standard) gradients and just counted the peaks that they saw. Using a D20 let's call it "low field" to differentiate it from the next generation of D20 Orbitraps, a system with an approximately 2 order intrascan linear dynamic range - they could count over 100,000 peptides. 

This is funny today because people are routinely identifying more than 100,000 peptides in their single shot samples, but at the time it was a benchmark. We were only fragmenting 15,000 things with DDA approaches then. It demonstrated how much further we needed to go for complete proteomes. 

Now with today's fastest stuff, these authors - on one instrument just keep finding new stuff. Just by running the same sample with a different method. It should be humbling and exciting to see just how far we still need to go to actually "-ome (ALL the things) the proteome. Or frustrating, I guess, depending on who you are. Lots and lots of gold in this preprint. 


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