Tuesday, January 1, 2019

Cause no one ever asked for it! My favorite papers of 2018!

It's already time to break out my sequin jacket and end the year at the Laser Disco?!??  How did that happen??  I didn't get a fraction of the stuff I planned to do in the last 12 months done...logically, instead of working on those things I'm going to do my biennial review of my favorite papers of the last 12 months?  Meh. Whatever.

In no particular order!!


You're tired of hearing about it. So am I (not!). This is maybe gamechanger of the year, y'all. When you can boost the S/N of your low abundance ions by an order of magnitude or two, VERY good things happen. I swear I've got an 80% written draft waiting for some feedback so I can get it out the door to be summarily and rapidly rejected by my peers like every other thing I've submitted recently. Hint: BoxCar is great for proteomics, but it's waaaaaaaay better for other things. Where do you need dynamic range the most? BoxCar it!


We can't amplify stuff like those weird DNA people down the hall can with their PZR machines, or whatever they're called. With SCoPE we can -- sortof. You can amplify tiny amounts of DNA into loads of it and then you can use whatever super expensive, low quality, error prone sequencing technique you want to. SCoPE lets you leverage TMT reagents to the increase in interscan dynamic range to quantify peptides that are below the dynamic range you would get with MS/MS sequencing. SCoPE is a revolutionary idea and I don't think we've even started to explore the ramifications that it can have for us. Perhaps more important than the original SCoPE paper is mPOP that makes it a lot easier to do SCoPE (trust me, it's not a great project if you're rusty on sample prep. I screwed it up, I think, and that's why it's a robot's job now.)


If you haven't downloaded this marvelous piece of software from the Smith lab you are missing out. We use this every day -- and every week or two it somehow gets better.

Since MetaMorpheus came out this year, upgrades have landed like
FlashLFQ (crazy fast label free quan)
Crosslinking analysis!
And MetaDRAW (which hasn't been published yet, but I'm using right now). Once MetaMorpheus finds that PTM you didn't know was there, didn't think to look for, and totally didn't have to do anything to find (cause that's what it does -- BOOM! PTMs!) you can use MetaDraw to make sure it's real.

Yo. That looks like MetaMorpheus found me a darned acetylation! The team is super responsive, and loves to get feedback. I wrote them about a feature that would be really helpful for my work -- and the next time I updated MetaMorpheus (it sends you little popups that new builds are available!) the feature I needed was there. If you don't have it, you can get it here. 

FDR for Spectral Libraries!

Spectral libraries sure seem like the future of mass spectrometry again, right? While DIA methods are pushing the development, shotgun proteomics needs them as well and we're seeing great new stuff! MS-Ana is a great new engine (wait. where is the MS-Ana post?), FDR for MSPepSearch added in the NIST stand-alone and in development in other software where it's used, and we can keep on going on. Now that FDR is in hand and there are amazing new libraries like ProteomeTools -- I just need to get off my butt and start using them again. So should you!

More Proof that NanoLC is mostly dumb!

Okay -- sometimes I say something like "I need 10ug of protein to work with" and the person I'm talking to stares at me like I'm wearing an awesome sequin jacket and strobe lights on my head, but most of the time, people have MILLIGRAMS of protein to work with.  I LOVE this paper. NanoLC is likely the weakest link in your pipeline. There are alternatives. Let's not get caught up in dealing with these engineering atrocities as if they're something we can never do without. Evidence is mounting that they may cost us more in productivity than they provide us in sensitivity and this paper is the best one yet.

Biological Application of a Phase Constrained Orbitrap!

I hope hope hope hope the application of the phase constraint algorithms for Orbitraps is just around the corner. Remember the jump in speed we got when eFT was added? This looks like it could be bigger. Do I want 60,000 resolution in the same amount of time it takes my QE HF to do a 15,000 resolution scan? Yes. Please. Now. Thanks.

ProteomeTools PTMs!

Yup, I already mentioned ProteomeTools once. This project is too awesome. This study on the fragmentation of 20+ PTMs from synthesized standards is an absolute gold-mine. There is more to be learned about PTMs fragmentation in this one study than in any book on the topic in the world. No. I haven't read every PTM book in the world, but I'd go to this paper first.

On the topic of PTMs -- what about Chemical Proteomics?

Big, far reaching implications here! Multiple reasons this study is in Cell. You don't have to take the experiment as far as these authors here. Just considering the unmodified peptides that drop in concentration when they're drug treated as something of importance might be the thing to blow the doors open on your project.

I admit it. I'm obsessed with the idea of what we could do with real Clinical Proteomics.

And this is the study I carry around if I want to prove to someone that this isn't 10 or 20 years down the road. We can help now if we're given a chance to.

A re-evaluation of FDR demonstrates some scary stuff about it -- but also how to fix it!

I've noticed a famous software program has some new feature that looks like they took this study seriously. I haven't investigated.

Wow. This could go on all day. Unfortunately it's late, I didn't sleep a ton last night and I have to cut this here. It was an AMAZING YEAR for Proteomics. And I expect nothing but bigger and better stuff from you awesome teams out there revolutionizing all the things. 2019!!!! Let's go!

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