Friday, March 11, 2022

Blowing up your search space with the expanding role of acylation!


Crud....okay, well I WAS excited to read this paper....

I was excited because people have increasingly been talking about the role of acylations in various diseases. (I finally have proof in the reviewed literature that I can do top down proteomics thanks to an annoying multi-acylated protein that changes its subcellular localization depending on how it's acylated. Proof that I don't just read your papers, I can use your techniques as well! One take away from the metabolomics study is this: If you put up a sign in some historically poor cities that are largely infamous for illegal drug use that says "we will give you $200 for a tiny amount of your blood but only if you check a box on this form that says I DO NOT do drugs" some people will -- no joke -- actually check that box and give you blood for $200 who actually DO DO DRUGS! WTF, right? Who would have guessed??? So if you are doing a study on the link between different diseases and drug use, you should consider testing your control group for drugs even if they say they don't use them. Crazy, right? This does, in my mind, put a  question mark on more than a few studies out there where LCMS based sophisticated targeted or global untargeted analysis was not performed on the patient samples. I say sophisticated targeted because you can find a lot of craziness in the blood of people that are not covered in your standard historic drug testing panels. AND one of the most used colorimetric assays for testing illegal drugs can not detect ANY of the fentanyl based compounds and there are at least 3 in heavy circulation in my country today). 

Great, I wrote a bunch of words in the orange box, and now I don't have time to read this study right now! I'm not super excited to read about how important these 14 PTMs are especially considering how most of them are on my least favorite amino acids to consider yet another modification on. I need my trypsin to cut at lysines and I need my TMT to label my lysines and modifications that mess with either of those tend to end up not getting detected nearly as often. Cysteine mods don't exactly fill me with joy either. Does reduction remove that mod? Does this now mean that I can't use cysteine alkylation as a static mod? 

Important to think about, but as the authors note, we have some considerable technical limitations to consider. 

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