Why hundreds of thousands (millions) of unidentified MS signals matter!


The table above is a great breakdown of what I'm going to call "nextgen proteomics search engines" going forward.
SeQuest (and, yes, reviewer number 3, I'm going to continue to capitalize it this way for the rest of time. Typing it in all caps makes it seem like I'm screaming about how much I miss the 90s {which… admittedly…I do sometimes…} is just missing too many things. I don't first pass anything with it anymore. I first pass with MetaMorpheus, find my PTMs and then MSAmanda them (because I like the PD output and MS2Go. Unless…well…it's a complicated PTM and then I just MetaMorpheus and stop. Cause there are modifications that MM will find that are 100% real that nothing else will find. One of the coolest things is when a PTM changes the charge state of the peptide. Like so you add the mod and you lose a proton. And it adjusts for that mass/charge shift.
I'm lumping SeQuest with Sanger Sequencing going forward. As in, whatever was before "next gen".
And this cool new review provides loads of extra reasons for why!

Why is it Shot-Gun? I dunno. I do like that this is a great review of open searching algorithms and why they are so very critical for us as a field, and for biologists who are thinking about proteomics stuff.

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Is a peptide quantitatively measurable? Here’s how you find out!

Okay....are you guys ready for this one? I wish I could say I was, but it's too important for us as a field to not think about.... Matrix matching? "Analytical figures of merit"?? Hey! This is the proteomics party, don't you come in here with all your boring analytical chemistry validation stuff....oh.....ugh...okay.... (Yes. I had to make that. You're welcome.) Why is this (study) important? In part because it addresses 2 separate concepts that need to be separated -- and they're right in the abstract: "....Our results demonstrate that increasing the number of detected peptides in a proteomics experiment does not necessarily result in increased numbers of peptides that can be measured quantitatively....." What? First of all, this study is like 4 pages or something and it represents an absurd amount of work. SRMs and DIA experiments (QE HF, I think) and a bunch of different HPLCs and the matrices are all sorts of fun -- CSF and FFPE and yeast digest and maybe I mi..