Can we quantify a relationship between PTMs and phenotypes?

Here is an interesting line of thought -- can we map the relationship between PTMs and phenotypes?  It feels like a big step.  As a microbiologist in my past life, we often worked on the link between the genotype and the phenotype.  In bacteria, these things can line up pretty well, "this gene helps shape the bacteria's size or what sugars they can utilize."

They don't always line up, of course, but we often chalk that up to redundant mechanisms.  In eukaryotes, it is even worse.  We have fail safe after fail safe protecting essential functions.  We also know that our proteomes are orders of magnitude more complex than our genomes.  But what if you could take a step forward and out of the system and look at the PTMs and how they line up with phenotypes.  Would this assemble some sort of a bigger picture for what is happening?

This is the question that is examined in this new paper in MCP from Warren Albertin et al., out of a multi-department effort mostly centered at the University of Paris.

In this study, they use a lot of fancy statistics to analyze acetylation of proteins in yeast and look at the correlation between theses and the phenotypes of these yeast.  The differential was determined by 2D gels and the mass spec employed is an undisclosed detail.  I find this funny:

"Spots of interest were quantified using Progenesis software (Nonlinear Dynamics, Newcastle, UK) and identified using mass spectrometry (MS)."

Yeah, cause who cares what MS was used and how? ;)

It is clear that the statistics are the stars of this paper.  And it all appears to be quite good (and way above my head).  It is an interesting pixel into the potential of what the big picture could be here.

Pittcon update -- Elise Andrew has a booth!

Not really proteomics, just a random awesome thing I got in my Facebook Feed:  Elise Andrew, the founder of  "I fucking love science" will be at Pittcon giving out shirts and autographs.
Don't worry, I'm actually reading literature and have real news to put up here.  It's just been a busy week.

PITTCON next week

PITTCON kicks off in Philly on Monday, March 17th and runs through the 21st.  If you're unfamiliar, it is one of the largest conferences for lab sciences in the world.  With a projected 17,000 attendees for this year and nearly 1,000 companies demonstrating their newest developments.  Short courses are also available on everything from spectroscopy through drug testing.  One of the courses is an Intro to LC-MS for beginners.  The courses are a little on the expensive side ($300-$400) but there are multi-course discounts.  I've never been to this, but it always seems like something that would be a lot of fun!

Refined procedures for studies of ubiquitination --20,000 sites in 1 go!

Another cool paper in MCP this month is this gem from Udeshi et. al., out of Steven Carr's lab.  In this, the group reports their strategy and results from a fully optimized enrichment and analysis procedures for anti-di-glycine remnant studies.  The study in question was performed on SILAC labeled cells, demonstrating that these studies can be qualitative or quantitative.  All of the MS/MS analyses were performed on a Q Exactive and analyzed with MaxQuant.  The end result -- 20,000+  ubiquitination sites that can be identified/quantified in a single experiment.
As we continue to find more and more things that are affected by ubiquitination, I think this is going to be an extremely well cited paper for how to do this kind of study.  Definitely check it out!

CBTC at University of Toronto is open and looking for collaborators/clients wanting top-notch MS work

After some reorganization, the Center for Biological Timing and Cognition at the University of Toronto was down for a bit.  With new management and guidance,  is up and fully operational now and looking for clients and collaborators.  If you are looking for some top-notch analytical technology, as well as a skilled staff to run this for or with you, definitely check out this center.  You can follow this link to see what services they offer, but I can assure you that they are loaded with some great technology.

Besides an Orbitrap for Proteomics, they also have the capabilities for small molecule quantification as well as high tech fractionation and enrichment techniques such as off-line HPLC and capillary electrophoresis.

It doesn't end at mass spec either.  They've got DNA sequencers and thermo cyclers and all sorts of other goodies.

You can follow this link for more information or contact:  Dr. Suzanne Ackloo (suzanne.ackloo@utoronto.ca) or Ken Seergobin (ken@psych.utoronto.ca)

Can you use SIEVE for Top Down Data?

I started using SIEVE about 6 months ago.  And I feel like I'm finally doing label free peptide quan with grown-ups.  Yes, I'm biased, but I never personally cared about lining up my chromatography (and there definitely still are reasons not to, to be elaborated on later!!)
But for plain old peptide quan, nothing beats SIEVE coupled with Proteome Discoverer right now and the two just keep getting better (more details on this, later as well!)  Synergistically, you are talking about some awesome software on the way.
Anyway, I was recently asked if SIEVE could do quantitative top down data.  Never thought to check, or ask!  So I picked up some data files from the analysis of intact proteins dumped them in, and (BOOM!!!) quantitative data from intact proteins.  So, yes, when we finally get where we're going (LC-MS/MS analysis of intact proteins) SIEVE will be ready!

Proteomics of Clostidium toxin effects!

My old pals in the Clostridium world are getting some love in the literature this month!
In JPRs papers ASAP, we have a high tech study of the effects  Clostridium toxins on cells.  The work was done using a SILAC approach on an Orbitrap Velos system.  The paper is from Johannes Zeiser et al., out of Hannover Germany.

In depth profiling of the human placenta proteome

In yet another amazing paper out of our friends at the human proteome project, this new paper from HJ Lee et al., describes the comprehensive proteomic mapping of the human placental proteome.  Maybe we overuse the word "comprehensive" sometimes.  I'm not doing that here.  These proteins were fractionated by SCX, HILIC, and OFF-GEL.  They were isobarically tagged.  They were enriched for phosphopeptides and they were enriched for glycopeptides and on and on.  The result is the most comprehensive look at the human placenta that has ever been assembled.  The breadth of this work is just fantastic!

Big Month for Label Free Quan -- 2 new reviews!

In case you're looking for a new review on label free quan, this month you are in luck.  Both this month's MCP and this month's Proteomics (Wiley) feature reviews on the topic.

The article in Proteomics is from Matzke et al., out of PNNL and can be found here.
The MCP article is from Nahnsen et al., out of the University of Tubingen and is here.

ChemCalc -- Exact mass calculator

Whenever you get tired of all the drivel that is on the internet, take a step back and look at all the awesome services there are out there.  The UCSF Protein prospector has been out there forever and is just awesome.  How many of us still use it all the time?  Chemcalc is another one.  It may have been there forever, I don't know, but I was just introduced to it today.  It is a simple and flexible tool for getting your exact monoisotopic masses and isotopic distribution.  It is brought to us by Luc Patiny of the Swiss Institute of Chemical Sciences and Engineering.  You can find it here.