Sunday, December 18, 2022

DirectMS1 is back and compares favorably as a chemoproteomics tool!


Metabolomics people get away with working out networks and stuff often by using MS1 based quan. Sometimes at unit resolution. They have smart networks for it like the Momichaug or mummichaug or mamachug or whatever it is called (let's go with MC) 

If you don't know about it, you should, it's amazing. Here is my dummy's version.

What if you're doing metabolomics and you find 3 really cool molecules that your drug treatment causes a whole lot more of them to be detected (increased relative abundance). You're confident on the mass and the retention time and that there is more of them, but your identifications are sort of wobbly. 

 Ion A could be molecule in your library 1, 2 or 3

And Ion B could be molecules 4 or 5

And ion C you're pretty darned sure is molecule 6, but maybe 7

What MC does is takes the pathway information into account. And if one of the canonical pathways in your organisms involves direct links between molecules 1,4 and 6 where if you have more of #1 it would be weird to NOT have more of 4 and 6. So it says -- "yo, your molecules are 1, 4, and 6, duh" 

That wasn't what I was talking about. I was talking about DIRECTMS1 again! 

(from this great team that I truly hope is doing okay)

Thanks to this new paper! 

What's DirectMS1 again? Oh, that's where you identify your peptides from high resolution MS1, reassamble those peptides into proteins, take into consideration the quan of the peptides in the confidence of the protein quan and do proteomics really really fast (5 minutes in this Q Exactive HF(X? I forget) example.

See the parallels that made me think of a well established Metabolomics tool? 

What this team did this time is compare MS1 results of drug treated cells to chemoproteomics data acquired in the more typical and dramatically more slow MS1 + MS2 acquisition over hours of time.

Could it possibly compare? 

(I mean...I wouldn't be up at 4:30am typing poorly about waiting for THE SLOWEST ESPRESSO MACHINE IN THE WORLD  it if it didn't work...probably....)

It does really impressively well. The paper is open, you should check it out. Yes, there are proteins/pathways that using 100x more LCMS time did find that DirectMS1 did not, but you don't see real disagreement here. The paper is short and does get a little confusing for me toward the end (see the lack of caffeine/time thing) but what you also get is some optimation to speed up/improve the sample prep time as well.

Yo, question everything. 

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