ChEMBL

EMBL PhD Programme

We have just gone through the second yearly recruitment round for PhD students for the EMBL International PhD Programme, so I thought I'd advertise the programme.

Kinase SARfari is now live

Kinase SARfari is now live and online - free and open to one and all. We'll keep an eye on machine logs for the next couple of weeks, and so we may bounce it now and then. Please let us know if you have any issues with using it, and please tell us OS and browser versions for any bug reports.

The URL for kinase SARfari is http://www.sarfari.org/kinasesarfari

Full source code is also available, licensed under a very permissive Creative Commons licence. Mail us if you want this, but as soon as we sort out our downloads area, it will also be available from there.

The data in the backend database is in the process of being updated to a more recent data cut, and when this is done, we'll post details. We're also resurrecting the rhodopsin-like GPCR version. There is also an email address for sarfari support issues.

Software: Tube Exits for iPhone

Of potentially limited global interest due to the sole coverage of the London Underground Network (known as 'The Tube'). However, for me, it's super useful. I'm forever getting on a tube-train, then having to fight against the flow to get to my connection or exit. Wouldn't it be nice to unlock the secrets of optimal carriage occupancy? This app is very simple, enter your start and finish stations (alongside any interchanges if you want) and it will tell you what carriage to enter for a speedy exit. The interface is nice and clean, and the display of the trains pulling into the platform hold the interest of children (and Strudel the dog). Cost is £1.79, and there is a free version which covers the 12 busiest stations. Further details are on the website - www.tubeexits.co.uk

The Cost of Drug Research and Development?

I have just got an account to try out a cool patent database (more on this later in a future post, maybe), but it gave me a chance to do an analysis I had wanted to do for some time - well at least start the analysis. The basic question is - Is there a relationship between R&D expenditure and discovery output? (as judged instead of the usual measure of drug approval, but instead by the more frequent and hopefully 'leading indicator' metric of patent publication). Future drugs will be based on current and historical research efforts, and so, on an idealised basis, one would hope for an approximate correlation between the number of patents held and future revenues - this assumption is problematic for a number of reasons, primarily, there is a huge and wild variance on the 'value' of certain patents/products, primarily due to the presence of large blockbusters. A further motivation of doing this was to complement the analysis that are usually done on R&D costs per launched drug, and also as part of a general interest in identifying 'leading' indicators for drug discovery.

With all the mergers in the industry at the moment, this is clearly complicated, but I made the assumption, that for publicly traded companies the R&D funded research would yield patents assigned in the name of the public company; for M&A activities the assumption is that the sunk costs on discovery will be accounted for on the acquired companies balance sheets, and it would appear that many of the original 'acquired' patent filings are progressed under the acquired entities name (albeit probably funded from the acquiring companies current R&D costs). Anyway, the accounting and costing here is nothing but a gross approximation, but I am sure that within private companies, some real, properly costed calculations like this have been done. In fact, this is such a toy analysis, it may not even merit the storage on the hard disks of the blog-site ;)

Here are the data (for the 'largest' pharmaceutical company Pfizer, chosen because of their size).

Patent publication - total of 1) US granted and apps, 2) EU granted and apps, 3) WO apps

Research and Development Costs

I then looked for R&D expenditure per year (this was surprisingly difficult to do freely, quickly and accurately), so 1) it would be good to have these numbers readily available in the public domain and 2) there may be some errors in the numbers here! I then also corrected the expenditures to 2008 dollars (so as to take account of inflation, the measure I used here was GDP deflator (using the calculator on http://www.measuringworth.com/uscompare/ - I do not know enough to judge if this is the best approach, but it makes superficial sense). The basic effect of this dollar correction is to flatten out the cost per patent curve (as you would hope).

So what does the data say - well the 'R&D cost per patent', on average, over the period 2000-2008 is $10.2M. Of course this is an average for a specific company, and other companies may well be different average numbers for a number of reasons (e.g. a more prolific or restrictive corporate policy/strategy on patenting, changing patent strategies over time). However, to my eyes there are a couple of interesting features from these graphs. 1) There is a general correlation between absolute R&D investment and the number of patents published, and 2) There is not a significant lag between the R&D investment and the patent output (you could expect that it takes some time to a) make the inventions and discoveries, and then patent, and wait for the patent to publish), so to be honest I was expecting a lag between the R&D cost curve and the patent output curve, maybe of around two years....

Here is a graph of patent output vs R&D cost.

Here is the graph on 'cost per patent' as a function over time.

Anyway, there is a lot more interesting stuff that could be simply done with this data, including 1) For fully integrated companies, is there a systematic difference in per patent cost that reflects either a fundamental difference in patent strategy, or an underlying difference in R&D productivity, and 2) More detailed and appropriate slicing of patent data by those that are granted, maintained, etc.

Hit-The-Sack - Pt. XII. Mercure Grand Hotel Biedermeier, Vienna

This was the hotel used for the EMBL-EBI SME meeting in Vienna. It was my first time in Austria, so there was a little frisson of excitement as I registered at the front desk. There was a man at the desk who was trying to book cabs for 18, on a rainy night, so my check-in was slow and laboured, but at least I could purposefully pace up and down the hardwood floored lobby, while the concierge tried to find some transport. I have a huge pile of loyalty cards, which have never been of any use, but I handed over my A|Club card, was told I had an upgraded room, and was then sent on my way to my room.

The room was very impressive - two floors, four rooms, two bathrooms, almost like a little alpine cottage on the roof of a hotel. Edelwiesstastic in my book. The next morning, I commented on my fabulous room to my colleagues - it's probably fair to say theirs was less impressive than mine. So one of two possibilities - either the Chembl-og Hit-The-Sack series strikes fear into the hearts of hoteliers worldwide, or there is some merit in loyalty schemes and a cheeky grin.

Overall a very creditable 58%.

Software: Autograph for Mac OSX

After a stressful but educational upgrade experience for Snow Leopard on my Apple powerbook, I needed solace in some new software - something fun, useful and cool, the sort of thing I could use on my morning train and draw gasps of amazement from my fellow travellers. I couldn't find anything quite like that, but I did find Autograph from Ten One Design. There is a free version, which has a watermark, and a paid version (which doesn't) and costs about 7 of those 'greenbacks'. The watermarked one is pretty useless to be honest; however, the licensed version is really very good, and will now avoid the panic and cuss words that follow me finding I need to physically sign an electronic document. Oh, it needs Snow Leopard and a modern (black keyed) macbook pro with a trackpad.....

Papers: Drug Target Central

Here is a paper (subscription required). It is written by Lee Harland (Pfizer Regenerative Medicine) and Anna Gaulton (ex Pfizer, but now in the ChEMBL group at the EMBL-EBI). It is an overview of Drug Targets, and some of the general principles of 'druggability' and ways to assess target tractability for drug discovery. In particular, the challenges of data integration are discussed.

%A L. Harland 
%A A. Gaulton
%T Drug Target Central
%J Expert Opin. Drug. Disc.
%V 4
%P 857-872
%D 2009

Kinase SARfari - looking for testers

We are testing a number of interfaces to our data at the moment, and have just flipped Kinase SARfari to a public facing server. We are looking for some people willing to test the interface on a number of differing platforms, so if you are interested, please mail us.

An install package is also available, for those wishing to try things on their own machines (however, you'll need some experience in web server config, Catalyst (the MVC, not the modelling package), an Oracle database, and a chemical data cartridge...)