Friday, June 7, 2024

Searle lab Stellar preprint resolves a lot of questions about the new ion trap!


I tried to keep up on what was going on in Anaheim at ASMS, but it's hard to keep up when you're actually there. Not there is almost harder. I ended up with more questions about Stellar than answers, but - yet again - Thermo collaborators dropped a series of preprints throughout the conference.

This one really clarifies what this instrument is and can do

I knew from the architecture (ion trap on the back of what appears to be the phenomenal Altis + QQQ instrument?) that it was going to be crazy sensitive, and the headlines were clearly that this ion trap can hit >100 scans/second. 

What this preprint goes into is how you can use this for both global proteomics and targeted validation. They use the instrument in DDA mode with offline fractions to build a library and evaluate that versus gas phase fractionated libraries with DIA. And then they do the targeting. So...if you had questions, it looks like this instrument can at least do all the normal shotgun proteomics stuff. A lot of us old people had bad experiences with nominal mass instruments way back in the day. I swear, if I put enough LTQ XL MS/MS spectra into a program called Bioworks and ran a Sequest search (around 2009-2011, this was my workflow) I could literally generate proteomics data to support ANY hypothesis you brought my way. There was low accuracy, poorly matched MS/MS spectra for every peptide from every protein.

The first real way of estimating FDR wasn't published by Gygi lab until 2007 (link),  but it didn't get to me in any form I could use until I was running Orbitraps. And who uses target decoy for PSMs today? We all use intelligent deep machine intelligence thingies. It's easy to think that if we had these informatics tools maybe we'd have less fear of nominal mass instruments. Exciting thought and since this truly sounds like an instrument with a load of capabilities at a much lower price point than the other headline grabbing ones today, I bet we'll find out soon! 

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