ICSB 2010 - From design principles to genome-wide and that persistent gap in-between

I am back from the 11th International Conference on Systems Biology (ICSB 2010) that was held in the lovely cite of Edinburgh. A full week of talks dedicated to systems biology (however you might define it). Speaking of definitions, it was refreshing to note that no speaker spent much time trying to define the field this time around. Aside from the keynote lectures, there were constantly four parallel sessions (see program) so you were always guaranteed to miss out on something interesting. With the help of a couple of attendees we took some notes of the conference in a FF room. There is lots of notes to go through if you are interested but here a few of my favorite highlights.

Keynotes
From all the keynotes the ones I enjoyed most were from Luis Serrano, Mike Tyers and Aldons Lusis. Unfortunately, Sydney Brenner was scheduled but canceled last minute.

Luis Serrano talked about his lab's work on characterizing a mycoplasma species (notes here) using a multi-omics approach. They are trying to use available technologies to build parts lists and models of all aspects of this species. They have learned a lot by taking such a systematic approach on a bug with so few genes but there is no plan that I could see on how to follow up on all this work. I can see that many computational biology labs will use this data but it would be a missed opportunity if more labs don't continue to go beyond the omics limitations.

The lecture by Tyers (notes here) was also very much about omics. He talked about their recent effort (Breitkreutz et al Science 2010) to search for kinase-protein interactions in yeast and how hard it is, in general, to study signalling pathways in this way (promiscuous interactions, complex systems etc). From kinases he moved to drug-gene interactions and chemogenomics. In particularly he briefly mention some unpublished work on evolution and prediction of drug-synergy. This is topic that I am really interested in as an applied side of evolutionary biology (more on that hopefully soon).

Another keynote I enjoyed was from Aldons Lusis (see notes). His presentation centered on a strategy for association studies in mice (Bennett et al. Genome Research 2010). This sort of work is out of my comfort zone but I really like all the examples he gave of using this strategy to find loci associated with clinical traits or protein/gene expression levels. Maybe I should be trying to read Nature Association Studies Genetics more often.


Parallel sessions
I went to the sessions of "Functional Genomics", "Cell signalling dynamics","Parameterizing proteomics" and "Biological noise and cell decision making".  In the Functional Genomics session, Lars Steinmetz talked about genome wide analysis of antisense non coding transcription and David Amberg's talk covered the use of genetic interactions to study actin mutants (an extension from Haarer et al. G&D 2007).
I really liked many of presentations from the Cell Signaling Dynamics session, including talks by Walter Kolch, Timothy Elston and Nils Bluthgen. It was interesting to note that many people presenting were following a similar approach of first enumerating different models that could achieve the function they were studying and then finding the most plausible by elimination.
From the proteomics session the highlight for me was the really cool work presented by Christian von Mering. They have essentially compiled a lot of mass-spec data and used corrected spectral counts to estimate protein abundance for many different species. The data can be found at http://pax-db.org and some reported results are published (Schrimpf et al., PLoS Biology 2009 and Weiss et al., Proteomics 2010). Overall the message appears to be that protein abundance is more conserved across species than gene expression.
Finally, from the session on noise and cell decision I particularly liked the talk of Roy Kishony, on his lab's work with antibiotic response, and James Locke's analysis of sigma b promoters (Elowitz lab).

Bridging the gap
Besides all the cool science I come back from this meeting with the feeling that we still have this huge gap between the -omics work and the detailed 'design principles' pathway analysis. There is even such a tension between people working in these two camps that it becomes almost a joke. Maybe this is why it is so hard to define systems biology, each "type" of researcher sees it differently. Some would say that it is not systems biology if it is not genome wide, while others will claim that we don't learn anything with omics (just a parts list). In this meeting there were great examples of both camps using established methods to attack new systems but there is still no clear attempt to bridge the gap. How do we go from genome-wide to quantitative mechanistic understanding ? Maybe next year in Heidelberg / Mannheim (ICSB 2011) we will see both camps, at least, acknowledging each other.

HFSP fellows meeting (Tokyo 2009)

I spent last week in Japan attending the fellows meeting of the Human Frontier Science Program. I was fortunate enough to get a postdoc fellowship from HFSP to support my current interest in the evolution of signalling systems. The meeting took place in Tokyo and brought together people from all sorts of different fields and at different stages of their careers. This program funds postdocs but also provides funding to young investigators setting up their labs and for teams of PIs working on interdisciplinary projects.

This year marks the 20th anniversary of the program that also coincides with a period of change in leadership. Ernst-Ludwig Winnacker, current Secretary General of the European Research Council, will take over the role of Secretary General of the HFSP organization from Torsten Wiesel. Also, Akito Arima will replace Masao Ito as the president of HFSPO (press release). Probably because of this the meeting had plenty of political moments and speeches. Thankfully most of the people involved in this organization appear to be very lighthearted so these moments were not a burden.

The curse of specialization ? 

A core focus of HFSP is to fund interdisciplinary projects that involve people from different areas or that help researchers change significantly their field of research. There was some time for discussions about the future of the organization as well as the future of "systems biology". For me personally, these debates helped to crystallized many of my own doubts. I am a biochemist but spent 90% of my PhD doing computational work. At this point I feel very much like a jack of all trades and master of none. In my previous work I have mostly hit walls due to lack of data so I plan to spend the next few years leaning a lot more about experimental work. Still, it is hard to be sure of what is best for the future. How much should I sacrifice in productivity to learn new skills ? Is it best to work as a specialist in interdisciplinary teams or be trained as an interdisciplinary person (Eddy SR, PloS Comp Bio 2005) ?

The broad scope of HFSP was well reflected in the topics presented in the meeting (PDF of program). There were many interesting talks, like the keynote by Takao Hensch about "How experience shapes the brain", in particular during the very early stages of life. He showed amazing work about "windows of opportunity" in learning and how these can be manipulated genetically or pharmacologically. Still, when I was looking around in the poster session I could not help but feel a bit of lack of interest since most of the topics were outside my previous work experience. This brings me back to the topic of specialization. Isn't it upsetting that we have to specialize so ? I don't think I can read and enjoy more than a third of a typical issue of Nature. This is for me the curse of specialization, it focuses not only your skills but your interests and curiosity.


Tokyo/Kyoto

Aside from the science, this was my first trip to Japan. I really liked it and hope to come back one day with more time to explore. I loved the temples, gardens, food, colors and all the differences.

BioBarCamp wrapup

In the last two days I attended the first BioBarCamp here in the bay area in the Institute for the Future. There is a lot of micro blogging coverage of the event in FriendFeed and even some recorded video from Cameron Neylon (click on demand and pick BioBarCamp).

The meeting was fun due of the unstructured nature of the event and also because I got to meet a lot of people I knew only from blogs. Two highlights of the event were the talks by Aubrey de Grey (see notes and also Cameron's video above) and Jon Trowbridg from Google that talked about this.

There were four parallel discussions going on but I kept mostly with the open science and web tolls related talks. There are a couple of ideas that I take away from these discussions that I will mention below but in general these overlap with what Shirley already mentioned in her post.

Pragmatic steps for Open Science and web tool adoption
Kaitlin Thaney and Cameron Neylon talked about open science and data commons. Cameron in particular is making the case that we need to demand open data the same way we demand for open access to science articles. Although publishers will say that they already try ask for availability to everything required to reproduce the results the truth is that this is not really well enforced. Funding agencies should provision funds to make raw results freely available for re-use once an article is accepted for publication.

On the side of web tools for science, Ricardo Vidal (OpenWetWare), Vivek Murthy (Epernicus), Jeremy England and Mark Kaganovich (Labmeeting) discussed user adoption. Adoption rates among scientists tend to be slow and there is a large generational gap. Again here pragmatic steps need to taken to promote the usage of these tools in science. Some of the current problems include fragmentation of user base, lack of focus in tool development, too few security restrictions.

These tools should try to focus on solving a few important problems really well. Examples of these problems include finding the person in my network that might have some expertize that I need; better ways to find articles that I find relevant or to manage my lab notebook and article library, etc. To reduce the fragmentation of user base it would be great that these websites find a way to share the social graph.

Finally the question of privacy online was again revisited. The idea of having open lab notebooks that anyone can see (as in OpenWetWare) might be a bit too radical and put away users that want to try the tools without the risks associated with exposing your research online. As has been discussed elsewhere there are advantages in having electronic notebooks (easier to access, share with peers and backup) but very few people will risk having their lab notebooks freely available online. Therefore allowing for privacy should increase usage.

ISMB 2008

I am leaving soon to Toronto to attend ISMB 2008. I usually stay way from big conferences since typically in small conferences is easier to really have time to talk to everyone. The nice thing about attending a big conference is that it looks like everyone is there. There is no shortage of science bloggers attending and it is going to be nice to get to know the people behind some of the blogs for the first time.

There is a room in FriendFeed were several people attending are gathered and for those not going it will probably be a good place to check for coverage of the conference. Alternatively here is a list of bloggers that are attending ISMB or some of the conferences before/after it:

Adam Kraut

Michael Kuhn
Daniel Jurczak
Neil Saunders

Sourav
Roland Krause
Shirley Wu
Jason Stajich
Ruchira S. Datta
Lars Jensen
Gary Bader

Let me know if I am missing anyone.

Life Sciences Virtual Conference and Expo

IBM Deep Computing will hold a 2 day virtual conference on Innovations in Drug Discovery and Development (16th and 17th of April 2008). The talks will be recorded and available for playback for those that register. The focus of the talks will be on the impact of High Performance Computing for life science research. The current list of talks:

• Dr. Paul Matsudaira, Director Whitehead Institute Professor of Biology and Bioengineering, MIT : Advanced Imaging and Informatics Methods for Complex Life Sciences Problems
• Professor Jan-Eric Litton, Director of Informatics, Karolinska Institute - Biobanking : The Challenge of Infrastructure for Large Scale Population Studies
• Dr. Joel Saltz, Professor and Chair, Department of BioMedical Informatics, Ohio State University : The Cancer Biomedical Informatics Grid (caBIG™)
• Professor Peter J. Hunter, University of Auckland, Bioengineering Institute : Innovation in biological system simulations
• Dr. Ajay Royyuru, IBM Research, Computation Biology at IBM : Update on the IBM Genealogy Project co-sponsored with National Geographic
• Dr. Michael Hehenberger, Solutions Executive, Global Life Sciences : IT Architectures and Solutions for Imaging Biomarkers

ICSB 2007

I am attending the eighth International Conference on Systems Biology (ICSB 2007) in Long Beach. I typically prefer smaller conferences but this one is probably the best one to get an overview of the recent progress in systems biology. As expected the program has a broad scope and unlike last year's meeting there are no parallel sessions so I will have a chance to ear more from others fields. Any other bloggers attending ?

Modular protein domains (an overdue wrap-up)

I did not even cover 1/3 of the Module Protein Domain workshop in my previous blog post. I will not attempt to do it know after so much time. The organizers were clearly concerned about keeping the information withing the participants so I will just post some of the general impressions that I took from the meeting.

Specificity profiling in high gear
There were several sessions dedicated to particular protein domains (SH3, SH2 and PDZ in particular) and for all of these there are several projects under way (or mostly completed) to determine the binding specificity of a large number of these domains (although in different species) using either phage display, spotted peptides and other methods. We should project ahead and start planning what to do with this information. How to combine this to predict pathways and pathway models with dynamical information. The work of Rune Linding is a a very good start at this (see NetworKIN).
Given that the methods are set up I suspect that the emphasis might shift now on exploring the evolution of binding specificities and the impact of disease causing mutations (i.e. profiling binding specificities of domain variants).

Good integration of different methods
Compared to the same meeting two years ago I had an impression that there was a better integration of different approaches (biochemical, structural, computational, etc). A particularly good example was the work of Michael B. Yaffe. There were plenty of structural talks (probably a bit too much) but I found particularly interesting the work of Ivan Dikic that presented extensive novel work on ubiquitin binding domains and Charalampos Kalodimos that presented his lab's work on potential functional roles of proline isomerization (Pubmed).
The computational part was well represented too and it was fun to see again Gary Bader and to get to know Philip Kim.

I hope to be there again in two years time to see how the field changed.

The biology of modular domains (day1 and morning of day2)

I am attending the 3rd (I think it is just the third) conference on modular protein domains. It is a small conference of just 80 people with a very nice environment for discussions. Given the nature of the conference I suspect that a lot of the talks will be about unpublished material so I will be light on the details since I have not personally asked people if I may post about their work.

In the first day of the conference on modular protein domains we had the opening lecture by Wendell Lim. It was a very light and interesting discussion of the evolution and engineering of signaling pathways. Lim started by discussing some interesting results coming from the sequencing of M. brevicollis, a unicellular choanoflagellate that is related to Metazoa and might provide some information about their evolution. It is a continuation of an analysis done by Nicole King and Sean B. Carroll that first identified a receptor tyrosine kinase in M. brevicollis, the first time one was identified outside of the Metazoa. The discussion was generally about the evolution of kinase signaling and how such a system of what Lim was naming "readers"~phospho-binding domains, "writers"~kinases and "erasers"~phosphotases can arise in evolution.
The second part of his talk was about the efforts to understand the evolutionary capacity of signaling networks by trying to engineer new or altered pathways. In this case the focus was on how with few components and small changes in these components it is possible to shape the dynamic responses of signaling networks.

Morning session of the second day

Synthetic biology
The Synthetic Biology sessions started off with a talk by David Searls on "A linguistic view of modularity in macromolecules and networks" (that was not very related to synthetic biology but nevertheless interesting). Searls detailed his views on the analogies between linguistics and biology. Here is a recent review by Mario Gimona on this analogy. At the protein level we could think of sequence, structure, function and protein role as similar to lexical, syntatic, semantic and pragmatic levels of linguistic analysis:

(Image reproduced with permission)

The general idea of building these bridges over topics is to be able to take existing methods and discussions from one side to the other (see review).

The second talk was by Kalle Saksela and again it had little to do with synthetic biology. Saksela's group is working on high-throughput interaction mapping for human SH3 domains against full proteins (human and viral proteins). They mentioned their progress in expressing and analyzing a subset of these interactions. He mentioned an interesting example were the Nck and Eps8L1 SH3 domain binding site in CD3epsilon overlaped with an ITAM motif such that the phosphorylation of the ITAM motif abolished binding by the SH3 domains. It is a nice example of signaling mediated by different types of peptide binding domains (see paper for details).

The third talk was by Rudolf Volkmer. He gave a short talk on a library of coiled coil proteins. The library contains many single mutant variants of the GCN4 leucine-zipper sequence. They then tested pairs mutants for heterodimerization by SPOT assays. Aside from a extending the knowledge of these domain family the library can also be used know as a toolkit of binding domains for synthetic biology (the work is already published).

The final talk on this panel was from Samantha Sutton from the Drew Endy lab. This was more like what one would expect from a synthetic biology talk . Samantha Sutton is interested in developing what she calls Post Translational Devices, general abstract devices that can regulate the post translational state of proteins in a predictable fashion. She has a page in OpenWetWare detailing her thoughts on this.

The second panel in the morning was about In silico computational methods.
Cesareni presented their ongoing efforts to experimentally determine human SH3 and SH2 interactions with spotted peptides. He then showed how this data can be used to search for examples where there is overlapping recognition by different domain types. The work is similar in methodology to the paper published by Christiane Landgraf and colleagues in PLoS Biology but know using two domain families and the human proteome.

Vernon Alvarez from AxCell Biosciences, gave a talk about a proprietary database called ProChart (that I cannot find online) containing many domain-peptide interactions tested by the company. He was basically promoting the database for anyone interested in collaborations.

The third talk was by Norman Davey author of SLIMDisc a linear motif discovery method. He is trying to improve their method, mostly by improving the statistics.

I gave the second short talk of the session. It was on predicting binding specificity of peptide binding domains using structural information. It is basically a continuation of some of the work I mentioned before here in the blog about the use of structures in systems biology but know applied to domain-peptide interactions.

The Biology of Modular Protein Domains

From tomorrow on I will be in Austria for a small conference on the biology of protein domains. I might post some short notes about the meeting in the next few days. I'll get a chance to present some of the things I have been working on about the prediction of domain-peptide interactions from structural data.

Here is one of these modular protein domains, an SH3 domain, in complex with a peptide:
The very short summary of it is that it is possible to take the structure of one of these domains in complex with a peptide (ex: SH3, phospho binding domains, kinases, etc) and predict their binding specificity. To some extent it is also possible to take a sequence, obtain a model (depends on structural coverage) and determine its specificity. I'll talk more about the details (hopefully) soon.

Synthetic Biology 3.0

I am not attending the 3rd edition of the Synthetic Biology conference but there are several bloggers attending and reporting.

The Seven Stones
Nature Newsblog (part I and part II)
The ETC blog (intro and part I)

The Seven Stones blog and more quick links

The Nature family of blogs as a new member - The Seven Stones - from the Molecular Systems Biology journal. I gave some help to set it up during my 3 months stay with the journal. Go over there and say hello to the editors :).

(via Deepak) The TED.com site was relaunched. It is has one of the most amazing collection of video talks available. The current main focus is The Rise of Collaboration.

(via Konrad and Richard Akerman) There was an interesting conference organized by Alen press - Emerging Trends in Scholarly Publishing. Both Konrad and Richard Akerman describe in their blogs what the conference was about and what they talked about.