Ummm….so on a scale of 1 to BioPlex — how big is your big proteomics data? Holy cow. You know, sometimes when you don't hear about these huge proteomics undertakings its easy to think "maybe they thought the first 10,000 human proteome interactomes was enough…"
NOPE. BioPlex is alive and well and providing human protein protein interaction data at a pace that doesn't quite seem possible.
Proof? Check out this new preprint!
Not familiar with BioPlex? It is a bulldozer type approach to human protein interactions. Instead of doing something complicated and elegant — why not just synthesize every open reading frame in humans and do an expert level immunoprecipitation — mass spectrometry experiment on them. Yeah — every one! BioPlex 3.0 showed about half the theoretical human proteome. For real.
It is a project so big and ambitious that is is easy to forget about. How do you take this another step forward? Well — you throw in some different cell types. And instead of looking at a few interactomes, you look at a few THOUSAND interactomes.
What on earth do you do with all that data? Besides make the most intimidating plots of all time (which you can do online at the BioPlex Explorer, here), well — this might be the biggest of the big data for proteomics right now. Did you need an excuse to buy that TensorFlow laptop and take that online course that keeps popping up on that sidebar you can't seem to block anymore on Reddit? To really explore this — we're going to need those artificial learning machine things — OR
— the BioPlex explorer is suprisingly powerful and intuitive!
Check this out — I've got a protein that is strongly dysregulated in a bunch of samples by both transcript and by proteome. It seems important, but it's been confusing. I'll just put that into the BioPlex explorer — BOOM –visualizations of protein-protien interactions!
Okay — so no surprise to me — this thing has a done of direct interacting partners. One thing that is cool and new here is how different this family of interactors is between the BioPlex 3.0 and the new HCT interactome.
If I didn't know what this protein did BioPlex provides that information and the data is all directly exportable in several formats — and links directly to AMIGO (which was undergoing maintenance stupid early in the morning when I was writing this)
Around these very practical resources the preprint paper makes some very impressive solutions regarding the human interactome — and — let's just say that the interactome doesn't shift on a small scale. The interactome appears to shift on a completely global scale. Which…has some definite ramifications, right?
How many times do you get an IP-MS (AE-MS) that is a pulldown from cell line A and cell line B? Hopefully the main characteristic of that cell line, for example, say homozygous KRAS weirdo terminus in B vs wild type in A? Hopefully that main protein is driving the change in your protein-protein interactions for your bait. But….if you've globally shifted the entire interactome? How does that change your results and confound your downstream interpretation? Way too big picture for me, but something that we need to keep in the back of our minds. Biology is complicated…
TL/DR: BioPlex is growing and is a shining example of what proteomics can be. Send this paper to every biologist you know. My guess is that it's going to be in a big journal pretty soon.
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..