The European Bioinformatics Institute (EBI)

If the pompous title caught your attention, and you are ashamed of that: Don’t worry. It is all true. My cheminformatics and metabolism group at the European Bioinformatics Institute (EBI) is looking for a phd student this year and all you need to do is apply through the regular route.  The range of possible topics is wide open, going from metabolomics via automated structure elucidation of metabolites to mining chemical information from the printed literature, and more. Your own suggestions are of course welcome.

The EBI is the world’s largest open provider of biological and chemical information.We are located, together with the Sanger Institute for Genome Research, on the beautiful campus of Hinxton Hall, a few miles south of Cambridge.

One of the small lakes on the Wellcome Trust Campus in Hinxton

Our PhD students are enrolled with the University of Cambridge.

The important part for now: The application deadline for the Fall PhD selection is July 15, 2009. And: Please drop me a note if you applied.

The workshop itself was phantastic – we had 40 participants with well balanced contributions from industry and academia. The first half day was dedicated to tutorials on various aspects of CDK, basic installation, our CDK and Oracle-based chemical search engine, scripting of CDK from within Bioclipse and CDK-based workflows in KNIME. The second day brought talks about science and applications based on CDK by John van Drie, Asad Rahman und Oliver Karch.  I reported earlier on those talks.

This official part was followed by a developers workshop in the format of an unconference.  Participants suggested topics on the fly and then voted with their feet. The topics that then made it where:

• Clojure
• Mining ChEMBL with CDK pharmacophore stuff
• Threading group
• Top 10 improvements (CDK WS 2009 unconference)
• JChemPaint/Rendering

all of which reported their results on the CDK wiki.

Another important outcome was a movement to join forces in creating and maintaining joint CDK-based plugins for KNIME and Bioclipse. There is a lot of synergy to be harvested. Licensing problems will need to be overcome but that seems doable.

As anyone can read on our CDK homepage, the CDK was started because my old compchem java classes that I had written for the first version of my structure elucidator SENECA and which where also the basis for the first JChemPaint releases needed a re-write (they where actually not bad and pretty fast, but not really object-oriented). By that time, friend Egon had come on board and so we took advantage of a joint visit to Jmol creator Dan Gezelter at Universtiy of Notre Dame to start the redesign. Unfortunately, we lost the two screenshots from Dan Gezelter’s whiteboard at nd.edu where we sketched the object hierarchy which is still largely in place today.

So, here is the current status of CDK in numbers:

• In September 2009, CDK will turn 9 years old and we already start planning for the 10th anniversary workshop.
• Its code base is more than 90,000 lines of code in more than 900 classes and over 9000 methods.
• As of today, 20/04/2009, CDK on Sourceforge has 67 registered developers and
• 86 (111) people are subscribed to the cdk-devel (cdk-users) mailing lists.
• According to Ohloh, CDK is now worth $ 4.6M and took an effort of 84 person years to create.
• The CDK article published in 2003 has been cited 68 times according to Google Scholar (I could not get my VPN to work so I do not know what WebOfScience says about our current citation count)
• According to SourceForge, CDK has been downloaded 90,000 times since 2001.

On the first workshop day, we’ll have tutorials on

• How to get started with CDK, given by Egon Willighagen
• CDK and databases, by Mark Rijnbeek
• CDK and Bioclipse, by Ola Spjuth
• CDK Workflows in KNIME, by Thorsten Meinl and Bernd Wiswedel

followed by the workshop dinner and a second day with scientific talks John van Drie, Asad Rahman and Oliver Karch.

The final discussion will include a presentation by Mark Forster, Syngenta, on his observations on the usability issues of CDK in industry. We also owe Mark a lot for creating the freely distributable linux image with the CDK and all the CDK related software used at the workshop.

On Tuesday afternoon we’ll have a developers workshop, which, traditionally, has the format of an unconference. The ideas for this format are taken from a concept called “Open Space Technology“, which we only discovered after having practised them for more than 5 years . To be fair, OST conceptualizes things nicely and relieves one from figuring out how to run meetings as openly as possible. Citing from the Wikipedia articles linked above, the idea is to have a facilitated, participant-driven conference centered around a theme or purpose, in a self-organising process; participants construct the agenda and schedule during the meeting itself.

A facilitator (me in this case) introduces the principles of OST to the participants. Participants then write the title of a session they would be interested in on a piece of paper, walk to the front of the auditorium and announce the title. If a participant proposes a topic, he or she should be passionate enough about the topic to lead the respective session.

OST philosophy is based on four rules and a law:

1. Whoever comes is the right people: this alerts the participants that attendees of a session class as “right” simply because they care to attend
2. Whatever happens is the only thing that could have: this tells the attendees to pay attention to events of the moment, instead of worrying about what could possibly happen
3. Whenever it starts is the right time: clarifies the lack of any given schedule or structure and emphasises creativity and innovation
4. When it’s over, it’s over: encourages the participants not to waste time, but to move on to something else when the fruitful discussion ends

There also exists another tentative “law”, usually referred to as the “Law of Two Feet“ (or “The Law of Mobility”), which reads as follows: If at any time during our time together you find yourself in any situation where you are neither learning nor contributing, use your two feet. Go to some other place where you may learn and contribute.

Having said all this, I hope that this largest CDK workshop ever will be asuccess and most importantly fun for everyone. We’ll keep you informed at the CDK 2009 Workshop wiki page.

At least, the article informs us about lots of money being pumped into another collaborative effort to exploit systems biology to make better drugs, which might be a good thing. I’m having a hard time to understand the fundamental difference between this and existing open approaches, but I’m happy to learn. Part of this lack of understanding comes from a lack of meat in this article. Maybe one of my readers can comment.

We are glad that the EBI Industry Program as well as the EBI outreach and training department are sponsoring the event. This means that things will be much more organized as they used to be . We are going to have one day (lunch time to lunch time the next day) of tutorials on how to use CDK and talks on research using the CDK. Afterwards, we’ll have our usual free-form developers workshop for the rest of the second day with all the usual fun. Both the evening of the 20th and the 21st will be opportunities for enjoying refreshments. We also have a small nominal registration fee of 50 Pounds to cover the costs for the workshop dinner and other food and drinks.

But this one was different and since this is a blog partly concerned with science in general, I would like to recommend to you “The Trouble with Physics” by Lee Smolin. The book’s subtitle is “The rise of String Theory, the Fall of a Science, and What Comes Next”. You, likely to be a member of some molecular informatics community, may ask, who cares about String Theory, and you may be right at a first glance. This book, however, is about Science in general, the mechanisms that drive it, and about what can go wrong. It is as much a book about science, physics and string theory as it is about the people in science and how they shape the fate of their field and more importantly of the rest of the pack working in it. It if fascinating to follow Smolin’s account of the rise of String Theory as one of the leading theories in physics. It is frightening to realize that 20 years or more of String theory has, if we believe the book, not lead to a single, novel, unique prediction that has been verified afterwards by experiment.

But while the account of the rise of String Theory was very entertaining and informative to read, the rest of the book, dealing with questions of the alternative theories, of science sociology, what science really is and what we can do to keep a finite possibility of fundamental revolutions, is even better.

I’m going to stop here because I feel that this book, once you’ve started reading it, will speak for itself.

At EBI, I will re-establish my research group and become leader of the chemoinformatics-related service teams, including the ChEBI and Reactome teams.

Future Directions at EBI

All of my ongoing research projects (SENECA, Bioclipse, CDK) will be continued at EBI and constitute a solid base for the rapid formation of a strong research group.

In addition, there is a plethora of fascinating modeling and data-analysis projects to be envisioned in Systems Biology in addition to the final grand goal of achieving a whole-cell or even whole-organism metabolic simulation. At EBI we will pursue the implementation of a metabolic simulation environment, with the goal of creating novel approaches to drug discovery. The “one-target, one-drug” paradigm still followed in many pharmaceutical chemoinformatics studies presented at conferences has clearly not lead to an increased number of drugs on the market and it is most importantly not capable of preventing failures of novel compounds in late clinical trials. Only a systems biology approach to drug discovery, taking into account transport phenomena, the interaction with all or as many targets as possible may allow us to make correct predictions.

To alleviate the abysmal lack of chemical data in some crucial areas of Systems Biology, we are interested in text, or better, publication mining techniques. In an ongoing collaboration with the Center for Molecular Informatics at Cambridge University, we will aim at creating an automated workflow for the extraction of molecular structures and data from the printed literature – past and present.

The Steinbeck Group offers PhD student positions via the EBI’s PhD program in 2008. Applications need to be submitted by Dec. 17 2007.

As leader of the chemoinformatics-related service teams at EBI (ChEBI, Reactome, etc.), my emphasis will be to enhance the existing resources with complete chemical semantics and raise funding for a substantial growth of the resources while securing their quality. The chemistry-related databases at EBI have the chance to become a valuable resource in pharmaceutical and medicinal chemoinformatics and serve as an integration point between chemo- and bioinformatics.

… and this hope is called (surprise!): Open Standards and Free Software. In this particular case, the latters come down to free as in beer, but that’s another story.
I’ve blogged about using HTMLSlidy together with ASCIIMathML, which proved to be an invaluable tool for authoring lectures ever since.

Another obvious advantage of HTMLSlidy is the possible use of applets in your slides. In one of my recent lectures on QSAR descriptors, I wanted to reproduce a table with chemical structures and descriptor values. First I had these structures as SMILES in a column but then quickly realized that rendering these SMILES as “real” 2D diagrams would be easy with the right applet. JChemPaint proved to be out of order once more and I therefore turned to MarvinView for this pupose (Rich – how is FireFly doing?).

The result is online a few slides after this link. The performance could be better of course. It definitely takes too long to load slide number 15 of this lecture, containing the 5 applet instances, but it is a step forward.
The HTML for the inclusion into the page is follows. It requires a java script library declaration at the beginning of your Slidy source code as:

<script language="JavaScript1.1" src="applet/marvin.js"></script>

Where ever you want your structure now, you put:

    <script language="JavaScript1.1">
    /<!--
    // marvin_jvm = "builtin"; // "builtin" or "plugin"
    mview_begin("applet/", 100, 100);
    mview_param("molFormat", "smiles");
    mview_param("mol", "CC(C)(C)CC");
    mview_end();
    //-->
</script>

I also found it handy to include an addendum slide with a MarvinSketch applet instance at the end of my presentation which I can use for producing SMILES, mol files and SVG graphics for my presentation while I’m authoring.

Checkout my lecture on computer-assisted structure elucidation at wiki.cubic.uni-koeln.de/lectures/CASE.The first instance of use of ASCIIMathML can be found on slide number 13.
The code which produces eq.1 on this page is

$S=sum_{i=1}^{N_q} frac{100}{N_q} - Delta_i$

for all $Delta_i > frac{100}{N_q}$   (Eq.1)

All you need to do is to download ASCIIMathML.js and include it into the <head> section of your HTMLSlidy presentation as

<script type="text/javascript" src="ASCIIMathML.js"></script>

directly behind the reference to slidy.js. The end of my HTMLSlidy header now looks like

<script src="slidy.js" type="text/javascript"></script><script type="text/javascript" src="ASCIIMathML.js"></script></head><body>