FEBS Course on Modular Protein Domains (Update)

The course finished some days ago and I just want to note down some of the interesting lectures. Nodalpoint has a discussion on blogging abut conferences. Should we talk about unpublished results presented in meetings ? Because it was such a small meeting with such an informal environment I will only mention work that was apparently finished.

Several talks were about domain specificity. How to define interaction specificity in the cell and what is the importance of domain specificity. For example, Cesareni talked about their work on the SH3 domains of S cerevisiae and how they have been using SPOT synthesis to discover the specificity and cross talk of the different domains. Sachdev Sidhu presented a study on PDZ domains of C elegans characterized by phage display. The study will give us a very large dataset of domain binding profiles and a look at the evolution of PDZ domains in C. elegans.

All this "simple" domain specificity has to be put into context if it is going to give us some biological insight. This issue was brought up by Rune Linding and Gary Bader, among others. We should add all possible information that is available in the species of interest and carefully combine them.

Rama Ranganathan gave a talk on the evolutionary constrains of a protein fold. The talked was centered on the PDZ domain but the methodology and concepts apply to any fold. He showed how one can use statistical coupling analysis to discover the positions in fold that are evolutionary correlated. This positions give us additional insight on the function of the fold.

Wendell A. Lim gave a fascinating talk on modular logic of cell signaling systems (buzzword: synthetic biology). His lab is working on modular allosteric protein gates and signaling rewiring. Most of what he talked about his from a recent review.

FEBS course on Modular Protein Domains

I am attending a FEBS course in Seefeld Austria on Modular Protein Domains.
I would like to highlight so far the short talk of Rune Linding on synthetic biology. He is working in the lab of Tony Pawson trying to develop a pipeline of generation of functional proteins from combination of domains.

One possible important outcome of this meeting might be the definition of some common cloning strategies and sharing of wet lab databases of cloned "parts". This will allow for an "open source" type of synthetic biology where everyone will be able to take advantage and built on top of other people's work. This would speed up innovation in a field that so far has produced interesting results of yet little useful applications.

Chimp genome hype

Last week Nature journal dedicated a lot of the issue to "celebrate" the release of a draft version of the chimp genome. Why all this hype ? The amount of attention a genome sequence receives nowadays inversely correlates with the divergence time from human. The only outliers are genome of species related to human diseases or human habits. We want desperately to understand what makes us "different" but I am not sure that solving the chimp genome will actually tell us much about this.

We can benefit from a sequenced genome in two general ways: 1) provide a guide to the experimental work done with a species and 2) use it for comparative genomics studies to help highlight general principles. Clearly the chimp genome will be of use for people working on chimp biology but I doubt that the chimp genome can tell us much about the human species, simply because we are not actually that different and the small differences will be hard to find. I say this because the molecular basis for the changes that make us "unique" are most likely regulatory changes and these are very hard to spot by comparative genomics alone, particularly if the genomes used are of species that diverged recently from the species of interest.

It comes also of little surprise that the most interesting points about the comparative human-chimp analysis, described more in detail in accompanying articles, relate to evolutionary events that occur at a fast rates and can easily be detected, big changes in chromosomal arrangements.

A lot of discoveries will still be made with comparative genomics but it seams we are reaching a point when another genome adds more statistical power but reveals little surprises. Maybe we could focus some of the efforts and resources to gather other high throughput data like protein interaction networks, transcription factor binding sites, expression data ...

The same way we gain so much with comparative genomics we might gain a lot with the ability to compare different protein interaction networks.


Some thoughts from Bioinformatics blog

A reflection on scientific journal publication by Philip Bourne

Philip Bourne wrote a very interesting perspective in the last issue of PLoS Computational Biology. He starts by comparing the somewhat convergent evolution of journal publishing and database submissions: "The daily work of any high-throughput scientific journal or biological database consists of information input, information processing, and information output." He also mentions the obvious difficulties of retrieval of information from scientific publications when compared to database data and raises some possibilities on what can be done to improve this. One would be to attribute digital object identifiers (DOI) to the items of content within biological databases. This would allow to track different publications referring to the same items to more easily retrieve the information from a paper automatically. Barend Mons wrote recently a commentary about exactly the same subject in BMC bioinformatics so there might be some grounds for agreement between some journals.
Phil Bourne also proposes that data in a publication should be more "alive". This reminded me of a recent discussion we had on Nodalpoint over reproducible research. Lastly Bourne also suggests that more data should be attached as meta data to the paper. As an example he suggests that gene names can be automatically retrieved and reviewed by the author with minimal effort and integrated with the paper as meta data. This point seems to me quite similar to first one, it would serve in essence to make it easier to retrieve information from a scientific publication.

It is nice to see the discussions coming up, now just find a way to get some journals together to agree on some formats and implementations. Make them opt-out, authors should do them or have to pay extra costs to have the publishing houses do it. Start making the papers on the web more connected to the databases, and vice versa. I want to click a protein name and have a list of possible databases to visit :). Add some kind of "trackback" to the databases, every paper mentioning a protein sends a trackback ping to the protein database and it is automatically updated.

Celebrating my first paper as a first author

The third issue of PLoS Computational Biology is out and in it is the first paper I publish as a first author. It took some time to get it published but I am grateful for the useful reviewer comments. The two main points about this work is that SH3 domains preferentially bind unstructured protein regions and that there is an "optimal" divergence time that one should consider when selecting species to use when looking for conservation of SH3 target sites. If you are interested in this last point I encourage you to read the excellent paper by Sean R. Eddy "A Model of the Statistical Power of Comparative Genome Sequence Analysis" in PLoS Biology.

The future of medicine

From the Personal Genome and Bioinformatics blog, here is a link to some predictions on the future of medicine by Leroy Hood.
I would resume his ideas to 1)you will have your own genome sequenced cheaply and 2)we will have nanotech tools in medicine.
These two things will make medicine more preventive and it will allow humans to live longer. You can say that the ideas where presented in an overly exaggerated way but both ideas have been going around for a long time and I personally see them as very probable. It would be useful to know your own genetic predispositions and I'm sure that engineered proteins and protein complexes will play a role in future treatments.

Another important point is that science should be visible to society. People like Leroy Hood and Craig Venter can sometimes come up with "funny" ways of promoting their investments/research but they also bring science closer to society.

Google Talk

There is a big buzz going around the web that tomorrow Google is going to release a IM service called Google Talk. The interesting thing is actually seeing the news going around the internet and geeks trying to connect to the service before it is available to the public. The image that came to mind was of a fire or a virus spreading fast. When they tried to get email users to switch they offered 1G of space, what are they going to offer tomorrow to make users switch to their IM ?

Update: Some beta version available here
Update 2: So there is nothing very special about it. The client is very simple and clean. The only interesting thing about this is not the client is the intention of making IM networks independent of the clients what makes a lot more sense for the users but I don't see yahoo and MSN messengers easily changing to a system like this and without them this is going to be very difficult.

The h index

From a Nature news I found this paper on the h index. J. E. Hirsch proposes that the scientific performance for a researcher could be measured by this index h that he defines as : "the number of papers with citation number higher or equal to h".
From the news: "n h-index of 50, for example, means someone has written 50 papers that have each had at least 50 citations."

Such a measure would take the journal out of the rating and stop the current "rich get richer" trend for the impact factor. This way the author will focus more on the audience of the journal.

On patent applications

In the last issue of Nature Biotech there was a list of recent patent applications in systems biology. Most of them are general ideas that have been published several times with different methods. I wonder how can a patent like this be approved and enforced when there are so many research papers available on the subject.

An example:
"A tool providing interactive capabilities for user involvement in extracting and disambiguating biological information in text; useful in generating a biological diagram."
A simple search for text mining in Pubmed will point you to more than 100 papers for example.

The same holds true for most of the other applications you can find in the table.

Here is the provisional abstract for the work of the first year of my PhD. To be published soon in PLoS Computational Biology.

Reproducible research with the publication of a "compendium"

From Faculty1000 (sub only) I found this paper, from the people of the bioconductor project on a new way to publish results as a document where code and words are woven together to create a "compedium". The document can them be browsed and the code changed in an interactive way. The authors give a concrete example using R packages and data from Golub et al. on cancer classification by expression data analysis.

I never used R so I'm still messing around trying to install everything to try this properly but at first glance it looks like an interesting concept. This way with the publication of results you would get immediately the methods, you could change parameters to check some hypothesis, etc. It would certainly help referees to check some ideas quickly. Something like this could also be used in-house as a personal e-lab book to keep track of code, data and ideas.

The first issue of PLoS Computational Biology is out. The journal's editors want this to be one of the main forums for the people working in the field of computational biology but so far what I would say is that it is nice to have another open access journal where we can aspire to publish our work.
I would like to point out the interesting perspective by Sean R. Eddy. Among several other interesting points he argues for interdisciplinary people instead of interdisciplinary teams and how the recent "big science" mentality might actually hinder innovation.

Tagging your research

Here is a commentary that will sound very familiar to most bioinformaticians, something that a lot of us have been talking about. It argues for tagging papers prior to publication to make the data available for automatic processing. It would not be so difficult to have the text read by a tagging program and have the author go trough a list of terms to quickly accept/change/reject them. The effort would be minimal to the individual author when compared to the required effort to curate databases with all the available and ever increasing published papers. Just imagine the nice tools that could be built with such information rich databases.

MSN messenger search

Another step in Microsoft's attempt to get into the search market :). The brute force way ... anywhere they can put a search tool for MSN search they will.

Rise of the Plagiosphere

This is an interesting article about the increase in awareness on the whole human knowledge. The basic statement is that there is an increase in our capabilities of searching through what is already been written and therefore the act of plagiarizing will be more apparent. The author goes on to state that this might increase our sense of futility. Our ideas will be ours no longer because most likely it has been thought of before and it is one click away.

I would say that there is an optimist side to this. More search capabilities also means an increased ability to share our ideas in the global village. I think innovation is very much driven by the ability to share and build on top of preexisting ideas. Therefore an increase in search capabilities for me sounds a lot like a drive for innovation.

Monkeys Brains Alter to Work Robotic Arm

More work from Miguel Nicolelis' lab shows that the concept of self is very plastic. They show the brain adapts by plastically dedicating some "brain structure" for the control of the robot arm.
He talked about this in his seminar in one of my phd courses. It does resonate well with our intuitive feeling about tools. If we move to a different keyboard, and it has a different layout we will be severely slowed down. People that drive a car most likely will describe the experience of driving like the car is somewhat an extension of self. They will probably look at the mirrors without noticing they are doing so, etc.
In this sense, becoming an expert with any tool will mean that we are incorporating this tool into our concept of self. This came into my mind when I realized once that I was using google in the middle of a instant messeger chat with a friend to look for something he wrote down instead of asking him about it. Is web search becoming an extension of our brain ? :) One day we will unconsciously stop storing information in our wet brain because it is there at simple recall distance away in our internet brain.

Modular machine assembles copies of itself in minutes.

Rather simple but elegant self assembly of robots. From the movie we can see a tower replicating by picking up pieces at predetermined places and putting them together to form a copy of itself.
It would look a lot cooler to have something like a "cube dispenser". All cubes should be able to communicate with each other. "dead" creatures should return themselves to the cube dispenser unit. "live" creatures all know were to get the cubes from and how to replicate themselves. Some mutations should be possible in order to make more complex creatures. Add some goals like the machine the moves more or the machine that can move some objects is allowed to replicate more.
With these simple type of rules and some more complex body parts they would start to have some very interesting robots.

Lights on Seattle

The move into city wide wireless coverage continues. This example is a very expensive, business only example, but I'm sure more will follow. In a couple of years we will have the broad band connectivity anywhere. I still feel that the man-machine interfaces are not progressing with the same speed but maybe with the connectivity availability more pressure to build new interfaces will come up.

Anyone interested in synthetic biology ? :)

taqdot: News for the open source and synthetic biology community

Grafedia: "grafedia: words written anywhere, then linked to images, video or sound files online"

Here is a nice concept. A physical hyperlink. You can "click" the real world to discover a hidden context. Sounds cool :)