Friday, January 17, 2020
Context specific FDR for top down proteomics!
On the bridge of the Starship Northwestern, Captain Kelleher and his crew are exploring the farthest reaches of proteomics, going where no lab has gone before.
I just had the worst idea ever -- and -- of course there is an internet tool where you can take anyone'es picture and "Trek" it.
What started this ramble? Well, while we're here on earth still struggling with accurate estimation of FDR for linear and slightly modified peptides, on the Starship Northwestern they're beaming down tools for accurate estimation of FDR for freaking intact proteoforms!
How are you currently assessing FDR for proteoforms? I'll tell you how I am. I'm not. I'm so pumped that I've identified a few dozen proteins from fragmenting their intact forms that I'm just popping them into my list. And -- I'd wager that is what basically everyone is doing outside the 4 labs that do top down proteomics each and every day. And if you've got an exact mass and some sequence information and you can check your 24 proteins that is probably even okay.
However, if you're really getting hundred/thousands of IDs? You need a real way to estimate these and this great new tool (which is freely available on Github here) provides a real starting point on these calculations. And it turns out that context is very very important.
The authors pressure test this tool using a true known sample and by reanalyzing some previously published materials to show that for today's top down proteomics both on earth and out there where they're exploring, this is the way to engage...