Wednesday, August 14, 2024

TermineR! Find endogenous proteolytic cleavage events in data you already have!

 



This is super smart, and if anything else can do it, I've certainly either forgotten about it or never heard of it.


What ARE all those other weird MS/MS spectra we don't match to anything? Gene variants are some, definitely loads of PTMs we didn't look for. How much of it is endogenous proteolytic cleavage? 

If you dose cells with a drug that induces CASPASEs to start self-destructing some of those cells, it can be a ton of it, right? But all those other enzymes? This is where it gets super cool.

They process some samples in FragPipe, which they tell you how to set up, and then decide that "FragPipe excels at finding weird cleavage sites" (paraphrasing) and then they use TermineR to figure out what is happening at these weird cut-sites. When comparing a WT mouse to a Pkd1fl/fl:Ksp-Cre mouse (copy pasta) which is a model of some nasty sounding kidney disease they find these endogenous protease activities are different between the two! 

Ever think of looking at whether a funny enzyme is cutting your proteome up in weird ways to see if that's your phenotype? ME EITHER. 

The downside is that the second "r" (the big one) in TermineR means you have to use the R thing, but it still might be worth it because I can't come up with another way to get to these data. 

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