Category Archives: Social

ISMB wrap-up (it was coming, we insist…!)

So ISMB 2015 seems a bit far away from now (just under 2 months!), but Dublin was an adventure, filled with lots of Guinness, Guinness, and … Guinness. Oh and of course, science (credits to Eleanor for the science of Guinness video)! We definitely had lots of that, and you can see some of our pictures from the week too (credits to Sam; https://goo.gl/photos/2qm9CPbfHtoC3VfH9)

Here are some key pieces of work that got to each of us here at OPIG.

Claire:
Jianlin Cheng, from the University of Missouri, presented his research into model quality assessment methods – ways of choosing the model that is closest to the native structure from a set of decoys. Their method (MULTICOM) is a consensus method, which calcualtes an average rank from 14 different quality assessment methods. By combining this average rank with clustering and model combination to select five top models for a target, their method produces good results – in CASP11, the group were ranked third when considering the top-ranked models and second when considering the top five.
Alistair:
Accounting for the cell cycle in single cell RNA-seq
The current ubiquitous of RNA-seq throughout academia speaks volumes to the strength of the methodology.  It provides a transcript-wide measure of a cell’s expression at the point of cell lysis; from which one can investigate gene fusion, SNPs and changes in expression, to name only a few possibilities.  Traditionally, these measurement are made using a cell culture and as such the expression levels, and derived results, are based on averages taken over a number of cells. Recent advances have allowed the resolution to increase to the point where measurements can now instead be made on single isolated cells. With this increase in capability, it should now be possible to measure and identify subpopulations within a given culture. However, the inherent variability of expression, such as that caused by the cell cycle, often overshadows any change that could be attributed to these subpopulations. If one could characterise this variability, then this could be removed from the data and perhaps these subpopulations would then be elucidated.
Oliver Stegle gave a great presentation on doing exactly this for the cell cycle. They modeled the different phases as a set of latent variables such that they are inferred directly from the data (rather than merely observed). Via this model, they estimated that upwards of 30% of the inherent variability could be accounted for, and hence subtracted from the data. Applying such a technique to culture of T cells, they were able to identify the the different stages of differentiation of naive T cells into T helper 2 cells. Crucially, these would of been obscured had the cell cycle not been identified. Given this success with just accounting for the cell cycle, Stegle suggested that their technique can be expanded upon to elucidate other sources of gene expression heterogeneity while making it easier to identify these cellular subpopulations.
Jaro:
Dr. Julia Shifman from Hebrew University of Jerusalem studies protein-protein interactions. In her 3DSiG presentation she focused on the presence of “cold-spots” in protein sequence where in sillico mutations to several different amino acids improve the binding affinity. Such cold-spots are often observed at the periphery of the complex, where no interaction is observed.
Malte: 
Alex Cornish from Imperial College London presented his work on the structural difference between cell-type specific interaction networks. To generate these, he weighted protein-protein interaction network edges by cell-type specific gene expression data from the FANTOM5 project. Using these cell-type specific networks, he finds that it is possible to associate specific networks with specific diseases based on the distances between disease-associated genes in the networks. Furthermore, these disease – cell type associations can be used to assess the similarity between diseases.
Jin:
Barry Grant presented an overview of the research activity in his group — namely nucleotide switch proteins (e.g. GTPases, such as Ras and Kinesin). In the case of Kinesin, the group used simple statistical methods such as principal components analysis to draw inferences between conformation and functional states. The group then used correlated motions to construct a community network that describes how certain groups of residues behave in certain conformational states.
Sam:
Discovery of CREBBP Bromodomain Inhibitors by High-Throughput Docking and Hit Optimization Guided by Molecular Dynamics
Min Xu, Andrea Unzue, Jing Dong, Dimitrios Spiliotopoulos, Cristina Nevado, and Amedeo Caflisch Paper link
In this paper MD simulations were used to confirm the binding modes found by in silico docking and to guide the chemical synthesis of hit optimisation. In one example three binding modes were observed during MD, which helped to identify favourable electrostatic interactions  that improved selectivity. For another compound a favourable polar interaction in the binding site was observed during MD, which helped to increase its potency from micro- to nanomolar. Thus, given a robust in-silico screening and docking approach, it seems that MD simulations can be a useful addition to confirm binding modes and inspire derivatives that might have been overseen in static structures.
Eleanor:
Bumps and traffic lights along the translation of secretory proteins
Shelley Mahlab, Michal LinialIn her talk, Michal described how a theoretical measure of translation speed, tAI, shows the differences between the translation speeds of proteins targeted to different locations. Proteins with a signal peptide (either secreted or transmembrane) have significantly slower codons than proteins without, over approximately the first 30 codons, perhaps allowing more time for binding to the signal recognition particle. Transmembrane proteins had a lower predicted speed overall, which may be important for their insertion and correct folding.

Le tour d’OPIG 2015

The third iteration of “Let’s use two wheels to transport us to many pubs” took place earlier this summer, on Wednesday 20th May. Following on from the great successes of the last two years, there was much anticipation, and the promise of a brand new route. This year we covered 8 miles, via the Chester, the King’s Arms at Sandford lock, the Prince of Wales in Iffley, and the Magdalen Arms. Nobody fell in the river or went hungry, so it was considered a success!

2015 route

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OPIG goes Punting!

Last Wednesday, it was the oh-so-very traditional OPIG Punting day (OPunting for those more acronym-prone).

photo

To my surprise,  the weather was spectacular! It was warm and sunny, a true perfect day for punting. We set off from our alcoves offices with determination in our hearts and, more importantly, with delicious snacks and a significant amount of Pimms and G&T.   Everything was set for a truly amazing day. 20140730_194600 Our group took over 5 punts from the Cherwell Boathouse, constituting what I like to think of as a small fleet of avid punters and merriment-seekers. We punted all the way up the Cherwell, past the lovely Victoria’s Arms into lands unknown (or into some grassy meadows in the vicinities of Oxford). Fortunately no keys were thrown overboard and no one fell off the punts (well, at least not accidentally). Yet, as usual, OPunting was very eventful! Following the customs of our group, we had the traditional punting race. I may have been too busy gorging on Pimms during the race, but if memory does not fail me, the race was won by Hannah (who can be seen in the photo bellow doing her swimming victory lap).

Hannah, in her victory lap swim...

Hannah, in her victory lap swim…

During the punting, we also discovered that Bernhard had some previously unknown Viking ancestry (Austrian vikings?), which manifested in an impetus to ram his punt against others. Suffice to say that he paved the grounds to “Dodgems Punts”, a ride that will become popular in fun fairs and amusement parks in 2027.

Other than that, the weather was so great that many of us decided to go for a lovely swim at the Cherwell.

Swimmers

After a refreshing pint at Victoria’s, we made our way back to conclude yet another successful OPunting day!

Le Tour de Farce v2.0

In what is becoming the highlight of the year and a regular occurrence for the OPIGlets, Le Tour de Farce – The annual OPIG bike ride, took place on the 4th of June. Now in its 2.0 revision but maintaining a route similar to last year, 9.5 miles and several pints later, approximately 20 of us took in some distinctly pretty Oxfordshire scenery, not to mention The White Hart, The Trout, Jacobs Inn and for some, The One and The Punter too.

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3035 – OPIG Beer & Cycling

Other than my customary Saturday morning hangover, today I woke up with aching limbs – so I am feeling rather poor indeed.  The source of this pain, other than the five and a half pints of premium quality Lager, is the OPIG beer and cycling tour of Oxford (aptly named, “Le Tour de Farce”).  What can I say, over here they make you work for your beer.


View OPIG Oxford Beer and Cycling in a larger map

We started off at the Medawar building, where we sit on weekdays and occasionally on weekends. Then we cycled to The Fishes, The White Hart, The Trout (the Carne pizza is a must), yet another White Hart, and the vegetarian and vegan Gardener Arms (I know, I know – I was drunk and they forced me in here).  For those not familiar with Oxford custom – these are some of the most beautiful (and pricey) pubs this land has to offer.

OPIG members love a laugh and their beer on the cycling trip

OPIG members love a laugh and their beer on the cycling trip

The bike hike (devised by Charlotte) was 9.535 miles.  On 5.5 pints of beer (Nick spilt his pint, like an amateur – so I gave him half of mine), that means I run on 13.86 miles per gallon  (9.535 / 0.6875).  So I roughly have the fuel economy of a 2013 Ferrari 458 Spider.  Say what you want about these blog posts, but you cannot say I am not thorough about the research which goes on behind them.

9.5 miles in Malta

This is how far yesterday’s bike ride would have got me in my country (Malta).

This morning I have also noticed my calves are an inch thicker in diameter, which of course means I will go and throw away all my socks and make that long overdue trip to the bicester village.  Perhaps I will cycle there.