Monday, June 15, 2015

SAPH-ire: Structural analysis of PTM hotspots!

Continuing theme alert!  What do we do with all of this proteomics PTM data?  Maybe we run it through this awesome new program from Henry Dewhurst et al., that they call SAPH-ire, or Structural Analysis of Ptm Hotspots.

What does it do?  Well, it is a way of looking at the post translational modifications you've uncovered in a a quantitative way and groups them to give you an idea of what they may be telling you.  Do I fully get it? Honestly, not yet.  But it seems really really smart and I think I'm on the edge of getting it.  Hopefully another coffee and it'll all fall into place.

I think this kind of thinking is critical, though.  Say I do a Byonic search and I end up with my proteins group of interest and in it there were 10 phosphorylations 16 lysine acetylations and 30 -odd other PTMs.  How do I get anything out of that?  If there was a way of clustering to say that "under these conditions you found more of these modifications" thats a big step forward, right?  And what if you could tell "under my conditions (drug treatment or whatever) that it wasn't a change in a certain individual PTM, instead it was that an area of the protein got PTMylated in some way..."  Maybe we're focusing too much on the individual modification rather than the fact that the region is active.

Okay. I'm another coffee in and maybe its just the caffeine euphoria thing but I think I seriously love this paper even though I'm going to need to keep thinking on it.  Check out this figure I stole from the Supplemental:

These are PTMs searched for in their proteins of interest (G proteins!) plotted against one another.  These are the protein "hotspots" that they focus on.  There are regions of these proteins that are active, but not all in the same way, or in a simple way.  We've got multiple PTMs occurring in combination in these areas and I've never seen anything that could provide this information before.

P.S., they validate the heck out of this thing.  I'm going to revisit this because I'm starting to lean toward thinking its positively brilliant.  Now, I just need to get my hands on it...

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