DIA-Umpire V2 -- Full support for Orbitrap data!

Mild confusion when I saw this article on GenomeWeb (original here). Cause I was honestly surprised that anyone had used the DIA Umpire for anything other than Orbitrap data -- but it was totally invented for SWATCH!

So...DIA Umpire V2 is now out and ready and, guess what(!?!?) it seems to be fantastic for Orbitrap data. A description of DIA Umpire V2 can be found in this brand new paper here.

Explain bioinformatics (or proteomics) to your grandmother!

...this paper needs more attention. Cause it is awesome.

Didn't Isaac Asimov say something to the effect of "if you can't explain it you really don't understand it?" I've looked for that quote before and not found it.

Anyway, this paper is awesome. Its a couple years old but it is cool enough to bring up and was bouncing around Twitter this weekend.

While we're on the topic of Atlases -- A great new review on the Human Protein Atlas!

Hey! Don't forget the other Atlas while everyone is talking about the low resolution one!  The Human Protein Atlas is an awesome huge resource that I visit frequently (mostly for cancer cell line data) but it has tons of stuff in it.

I'd never even seen the Mouse Brain Atlas until I went over for that image. Want to see some awesome microscopy? There is some stunning stuff in there -- and it is useful -- not to me, but to somebody for sure!

What was I...oh yeah!  A brand new review on the Human Protein Atlas from Cecilia Lindskog. It is a nice short read, and has a clinical tilt to it. You can read it (open access) here!

Don't give that big 'ol FTICR away just yet. They found some Helium!

Say Good-bye to the Helium shortage and Hello to your favorite 1 Hz FTICR again.  Researchers collaborating with an un-named entity found a huge reserve beneath the country of Tanzania. Hopefully this leads to cheap helium again and some economic gains for one of the world's poorest countries. Wins all around!

BBC article here. Wait. Is it still B-BC? Didn't they change their name or something recently?

SRMAtlas -- Tools to do SRMs on a bunch of human proteins!

Whoa! Finally got the full text.

I humbly present my interpretation of the HumanSRMAtlas that showed up in Cell last week.

Let me get this off my chest first. This thing has been around for at least 5 years, right? Seriously, I thought I'd been taking crazy pills, but then PubMed verified it:

GoogleScholar finds references to it going back even further than PubMed does. And this went into Cell!

With that out of the way!  What is this?

Its a ton more SRM assays!  They painstakingly developed synthetic peptides that would be representative of a large number of human proteins. They obtained MS/MS spectra for these synthetic peptides using some Q-TOFs and used multiple collision energies to assemble good spectra.

Then once they had this big library they picked a pathway that was interesting and they show that they can use triple quads to look at quantification of that pathway in human cells.

Will the SRMs still suffer from the same inherent problems of every low resolution MS/MS experiment ever done? Absolutely! But a lot of work went into minimizing this. Proof? Peptides from 7-20 amino acids long, they could identify with 96% success rate in their tissue (FDR ~4%) bigger peptides were more problematic (21-30 amino acids ~ 83% success rate), but remember this is SRM, you can always do more peptides.

Will interference be a bigger problem in more complex organisms like humans? Sure!

Will the quality of the data vary wildly depending on the body tissue? Of course.

But, this is a seriously comprehensive database. Loads of SRMs. A TON of work went into this and its a free resource out there at SRMAtlas.org!

Ben's biggest questions here -- presumably since this was designed with high resolution MS/MS, I wonder if this resource is PRM compatible for higher certainty, less noise, etc.,

Another awesome UVPD phosphoproteomics study!

I swear I'm almost going to stop reading papers where people have "hacked" their Orbitraps and added UV photo-dissociation to them. Maybe this is the last one.

This is (one of?) Jenny Broadbelt's systems it seemed like everybody at ASMS was talking about and described in this new paper by Michelle Robinson et al.,.

In this case they modify an Orbitrap Fusion (yikes!) and add UVPD to the HCD cell. They IMAC enrich phosphopeptides from cancer cells and alternate HCD/UVPD and investigate both positive and negative modes.

The HCD still wins in terms of most identified peptides (15k resolution MS/MS scans), but the UVPD peptides are highly complimentary to the ones identified via UVPD. The negative stuff looks the least efficient in terms of ID's per time, but identifies even more complimentary phospho peptides identified by the other techniques.

They use PD 1.3 and Sequest for the data processing. Part of me seriously wonders if they could do a lot better with the modified OMSSA Coon Lab has been using, or with the modified Byonic that was described a few weeks ago.

In the end, though, we're looking at another description of UVPD that shows it has enormous power. Unfortunately, no one is discussing commercial release. Looks like some of us here in MD need to buy a laser and a voltmeter and get rewiring. I've got a spare weekend coming up... (P.S., I'm mostly joking)

Masses4Masses.org

Mildly interesting -- and somewhat odd. Masses4Masses.org.

Might be interesting cause its got a pretty nice animation of mass spectrometry history. Might be leaning a little toward a particular set of technologies ---

Interesting perspective, right? If you were an outsider to the field you could scroll through this and think that ion mobility was the biggest technological advance in mass spectrometry for this century so far. Not to say that it isn't cool stuff. But...

...its like looking at a genomics website that breezes over PCR like it was some annoying stepping stone. "In 1995 some guys made unlimited amounts of DNA from virtually no DNA and some weird guys in Norway gave them a prize for it"

Seriously, pretty animations and some interesting videos. But it might be as slanted toward a particular technology as this silly blog is. ;)

Mission Critical -- Why Precision Medicine NEEDS proteomics!

I guess if you read into the image above it might seem like I'm implying something. I'm not. I just couldn't find a cool picture for "Mission Critical". This seemed much cooler!

What am I rambling about now? This cool opinion/review in Human Molecular Genetics. It is called "Mission Critical: The need for proteomics in the era of next-gen sequencing and precision medicine." YEAH!

Who is it written for? The HUGE genomics field and the users of this technology AND kinda for us. It is a great description paper of 1) Our technology 2) Their technology and 3) Why the interplay is critical.

It points out places where we can definitely interact -- such as mass cytometry (enriching and identifying cell populations by mass spec) -- as well as a few places where genomics techniques lack power that our instruments have.

Now...minor criticism of this nicely written paper might be that our current generation sensitivity and power might be downplayed a little. Sure, amplification based DNA/RNA techniques are super sensitive, but some next-gen techniques don't employ amplification. Compare where we are now in terms of the low copy-number proteins vs transcripts each respective field can identify and we're not far off -- and possibly ahead.

Wait, one more. You can tell the authors are coming from the genetics world in that the only times they mention modifications are when they discuss splice variants or single amino acid changes. You could argue that with the importance every study is showing regarding post-translational modifications in every disease we have looked at -- well, this is where mass specs are going to be indispensable in terms of precision medicine. Good luck PCR-amplifying that global shift toward deglycosylation!

Seriously, though. Well written paper with some good arguments for why our field needs to be considered in any initiatives toward precision medicine!

SRMAtlas -- Come on, PubMed, list this thing so I can find a full text copy!

Honestly, just leaving this here so I don't remember to read it once PubMed indexes it. I'm far too  lazy busy to find it in the stacks -- and I ain't paying $53 to read something about triple quads (no offense).  Seriously, though, Twitter has went kinda nuts about this paper, but I'm not sure anyone has read it yet.

When it is indexed I'm gonna say SRM-Atlast!

Proteomics approach finds other dominant virus proteins in Zika+ brains!

You could say that 2016 was the year of the Zika Virus. I'd honestly never heard of it. Friends from areas where it has been around for a long time made it seem like no big deal. Just another tropical virus you get sometimes (!!) -- but it has been implicated in some terrible stuff, including (terrifying!!) microencephaly.

According to this brand new, short report from Fabio Nogueira, et al., Zika virus may not be the only thing at play in the real nefarious stuff.

They got some brain tissue from brains that tested positive for the Zika virus by PCR, digested the protein and ran it out on a Q Exactive and looked for Zika proteins. And didn't find any.

They expanded the search to a much more comprehensive database...and found some highly expressed viral proteins -- from a different virus!! The virus is called the bovine-like viral diarrhea virus (BVDV-like) and they show nice fragmentation spectra in the e5s.

As a minor comment -- I don't think that we could say that the Zika virus proteins aren't there. Brain matter is going to be super complex and separation on a 15cm column for 180minutes is not going to provide ultra-deep proteome coverage, but this is pretty interesting. If we think of lethal viral models that hijack host cells and then produce tons and tons of themselves -- you'd expect the Zika proteins to be at high abundance. Or at least I would. It is at least super weird that another virus appears to be running amuck -- in the brain -- in 3 different individuals!

Seriously interesting and I'm glad this paper appears to be getting a lot of attention!!