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 missed one.

What's the point? Well, I think the goal was to set out and develop some powerful standard curves without heavy standards, but the quote above suggests a really powerful fundamental truth was kind of a side effect and it kind of steals the show.

We do a lot of relative quan stuff in proteomics. And....it's seriously just relative....and a lot of the results make no sense at all. And this study looks at an absurd amount of data and -- look -- some peptides are just not quantifiable in their background matrix. Real quan has things like linear dynamic range and other boring terms like LOQ/LOD/LLOQ/LLLLOQ and if you really dig into them the way this team did, there is only one solution --

"....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....." 

Same quote twice....? Why not.