Saturday, November 10, 2007

Predicting functional association using mRNA localization

About a month ago Lécuyer and colleagues published a paper in Cell describing an extensive study of mRNA localization in Drosophila embryos during development. The main conclusion of this study was that a very large fraction (71%) of the genes they analyzed (2314) had localization patterns during some stage of the embryonic development. This includes both embryonic localization or sub-cellular localizations.

There is a lot of information that was gathered in this analysis and it should serve as resource for further studies. There is information for different developmental stages so it should also be possible to look for the dynamics of localization of the mRNAs. Another application of this data would be to use it as information source to predict functional association between genes.

Protein localization information as been used in the past for prediction of protein-protein interactions (both physical and genetic interactions). Typically this is done by integrating localization with other data sources in probabilistic analysis [Jansen R et al. 2003, Rhodes DR et al. 2005, Zhong W & Sternberg PW, 2006].

To test if mRNA localization could be used in the same way I took from this website the localization information gathered in the Cell paper and available genetic and protein interaction information for D.melanogaster genes/proteins (can be obtained for example in BioGRID among others). For this analysis I grouped physical and genetic interactions together to have a larger number of interactions to test. The underlying assumption is that both should imply some functional association of the gene pair.

The very first simple test is to have a look at all pairs of genes (with available localization information) and test how the likelihood that they interact depends on the number of cases where they were found to co-localized (see figure below). I discarded any gene for each no interaction was known.
As seen in the figure there is a significant correlation (r=0.63,N=21,p<0.01) between the likelihood of interaction and the number of co-localizations observed for the pair. At this point I did not exclude any localization term but since images were annotated using an hierarchical structure these terms are in some cases very broad.

More specific patterns should be more informative so I removed very broad terms by checking the fraction of genes annotated to each term. I created two groups of more narrow scope, one excluding all terms annotated to more than 50% of genes (denominated "localizations 50") and a second excluding all terms annotated to more than 30% of genes (localizations 30). In the figure below I binned gene pairs according to the number of co-localizations observed in the three groups of localization terms and for each bin calculated the fraction that interact.

As expected, more specific mRNA localization terms (localizations 30) are more informative for prediction of functional association since fewer terms are required to obtain the same or higher likelihood of interaction. The increased likelihood does not come at a cost of fewer pairs annotated. For example, there are similar number of gene pairs in bin "10-14" of the more specific localization terms (localizations 30) as in the bin ">20" for all localization terms (see figure below).
It is important to keep in mind that mRNA localization alone is a very poor predictor of genetic or physical interaction. I took the number of co-localization of each pair (using the terms in "localizations 30") and plotted a ROC curve to determine the area under the ROC curve (AROC or AUC). The AROC value calculated was 0.54, with a 95% confidence lower bound of 0.52 and a p value of 6E-7 of the true area being 0.5. So it is not random (that would be 0.5) but by itself is a very poor predictor.

In summary:
1) the degree of mRNA co-localization significantly correlates with the likelihood of genetic or physical association.
2) less ubiquitous mRNA localization patterns should be more informative for interaction prediction
3) the degree of mRNA co-localization is by itself a poor predictor of interaction but it should be possible to use this information to improve statistical methods to predict genetic/physical interactions.

This was a quick analysis, not thoroughly tested and just meant to confirm that mRNA localization should be useful for genetic/physical interaction predictions. I am not going to pursue this but if there is anyone interested I suggest that it could be interesting to see what terms have more predictive power with the idea of integrating this information with other data sources or also possibly directing future localization studies. Perhaps there is little point of tracking different developmental stages or maybe embryonic localization patterns are not as informative as sub-cellular localizations to predict functional association.


Jansen R, Yu H, Greenbaum D, Kluger Y, Krogan NJ, Chung S, Emili A, Snyder M, Greenblatt JF, Gerstein M. A Bayesian networks approach for predicting protein-protein interactions from genomic data. Science. 2003 Oct 17;302(5644):449-53.
Rhodes DR, Tomlins SA, Varambally S, Mahavisno V, Barrette T, Kalyana-Sundaram S, Ghosh D, Pandey A, Chinnaiyan AM. Probabilistic model of the human protein-protein interaction network.Nat Biotechnol. 2005 Aug;23(8):951-9.
Zhong W, Sternberg PW. Genome-wide prediction of C. elegans genetic interactions.Science. 2006 Mar 10;311(5766):1481-4.

Thursday, November 08, 2007

What I don't like about BPR3

For those that have not heard about it before BPR3 stands for Bloggers for Peer-Reviewed Research Reporting. From their website:

"Bloggers for Peer-Reviewed Research Reporting strives to identify serious academic blog posts about peer-reviewed research by offering an icon and an aggregation site where others can look to find the best academic blogging on the Net."

It is all great except that it already exists and for a long time before BPR3. You can go to the papers section in Postgenomic and select papers by the date they were published, were blogged about, how many bloggers mentioned the paper or limit this search to a particular journal. I have even used this early this year to suggest that the number of citations increases with the number of blog posts mentioning the paper.

In this case I think that unless they really aim to develop something that is better that what Postgenomic already offers, the added competition will only fragment an already poor market. The value of a tracking site like Postgenomic, Techmeme or what BPR3 is proposing to create increases with user base in a non-linear way. This is what people usually refer to as network effects in social web applications. Increasing number of users make the sites more useful, reinforcing the importance of the social application. I suspect Postgenomic is not closed in any way to discussions. The code is even available here for re-use. So, why can't BPR3 and Postgenomic work this out and have a single tracking database and presentation. Let's say that BPR3 could be a mirror for the Postgenomics papers section (why re-invent the wheel).


I am not in favor of any particular site (sorry Euan :), what I think would be useful would be:
1 ) common standards for everyone (publishers, bloggers, etc) to carry information on published literature (number of times paper was read, ratings, comments, blog posts, e-notebook data, etc) attached to single identifier (DOI sounds fine)
2) one independent tracking site with enough users to gain hub status such that everyone gains from high exposure to the science crowd.

Thursday, November 01, 2007

The right to equivalent response

(disclaimer: I worked for Molecular Systems Biology)

The last issue of PLoS Biology caries an editorial about Open Access written by Catriona J. MacCallum. It addresses the definition of Open Access and what the author considers an "insidious" trend of obscuring "the true meaning of open access by confusing it with free access".

I agree with the main point of the editorial, that we should keep in mind the definition of open access and that the capacity to re-use a published work should have more value to the readers.

However, it is very unfortunate that the very fist example MacCallum picks on is the Molecular Systems Biology journal for the simple fact that very recently they have changed the publishing policies to address exactly this issue. Authors can choose one of two CC licenses, deciding for themselves if they want to allow derivatives of their work or not. See post at MSB blog. As it is explained in the blog post the discussions about the licenses actually started several month ago and I think the final implementation is a very balanced decision on their part.

Thomas Lemberger, editor at MSB wrote a reply to the editorial that PLoS decided to publish as a response from the readers. These can only be seen if readers decide to click the link "Read Other Responses" on the right side of the online version.

I am obviously biased but for me this is not really giving the right to equivalent response. It would not have cost them much to issue a correction or publish the letter as correspondence where it would have the same visibility as the editorial. This would signal that they are indeed committed to collaborating with other publishers and journals that support open access (as stated in PLoS core principles).

Bio::Blogs #16, The one with a Halloween theme

The 16# edition of Bio::Blogs is know available at Freelancing science. Jump over there for summary of what has been going on during this month in the bioinformatic related blogs. If not for anything else then just to have a look at the pumpkin. Thanks again to everyone that participated.
Paulo Nuin from Blind.Scientist has volunteered to host the 17# edition that is scheduled to appear as usual on the 1st of December.

Thursday, October 25, 2007

Building an e-Science platform with Miscrosoft tools

(via Frank Gibson's Peanutbutter) Hugo Hiden, the technical director of the North-East Regional e-Science Centre (NEReSC) started a new blog where he will explore how to build an e-Science platform based on Microsoft technology. The initial post explains a little bit why he is doing this:
"The reason for this blog is, primarily, to document my experiences with writing a prototype e-Science research platform using Microsoft tools instead of the more traditional approach of fighting with Open Source. This way is easier, supposedly."
and also, what he aims to build:
"The task I have set myself is to recreate, at a basic level, the software being developed by the CARMEN project (http://www.carmen.org.uk). "

Let's see how it goes. Maybe they'll take suggestions later on :).

Sunday, October 21, 2007

Bio::Blogs #16 - call for submissions

The next edition of Bio::Blogs (bioinformatics blog journal) will be hosted at Freelancing science on the 1st of November. If you find anything this month that you think is interesting to add to this addition send an email to bioblogs at gmail. com until the end of the month. Anyone interested in hosting future edition can also send an email to volunteer.

Friday, October 19, 2007

The Fortune Cookie Genome

*in an imaginary future*

Today is the day I get the sequencing results back. It is going be interesting to have finally a glimpse of my very own genome. At the same time I am afraid of the potential disease associations they might find in there. In any case I rather know it with time to do something about it. Thats it ... I exhale and open the main door to the building walking up the desk.

- Hi. I have an appointment with my genetic adviser.
- Oh yes, go up to the 3rd floor, they are expecting you.

I walk up a DNA shaped stairway and walk into the office of one of the attending specialists. He was the one convincing me of how useful it would be to purchase the GenomeSurvey(TM) package.

- I got your email. The results are in ?
- Yes, we have your genome fully sequenced and uploaded into your service of choice. I see you have picked Google Health as your storage provider as part of the package.
- Is there any bad news ? Will I have a serious disease soon ?
- I understand your concern. There is really nothing too serious, but I will come to that in moment. You may login with your Google account here and I can guide you through some of the results.

I login to my health page and I am confronted with the usual simple white-blue Google interface. I noticed the addition of a genome tab and let my adviser tell me more about it.

- As you can see, your genome as been uploaded to your account. It has also been submitted as an John Doe genome to the NCBI personal genomics database. You may select later to make your identity known and/or associate any of your personal history information to it.
- What about the disease associations ?
- Yes. So you can click here on the associations report to have a full listings of the phenotypic associations. You have a very healthy genome, no serious rare diseases. In your case the most important finding is that you have a 2% increased likelihood of developing a heart condition when you are above 60 and a 1% increased likelihood of having Alzeimer's disease after 65.
- That's it ? 2% ? 1 %?
- Well, that is assuming no prior knowledge on your diet and other personal history as established in the large HapMap version 10. From now on you may input into the forms provided in Google Health all your diet and other personal information on a daily basis and as the information accumulates the service will automatically update the probabilities. As your adviser I should tell you that this information can be used by Google to provide you with better targeted advertisement in all other Google products.
- Right ... is this it ? Does the package include anything else ?
- Of course ! As I mentioned to you before you can click here on the prescription tab to get an informal advice on how best to deal with the associations that were found for you. You should always discuss these suggestions with your doctor before doing anything. By company policy I cannot read this information with you, since we are not liable for this. You can read it at home when you get there.
- Well , if there is nothing else I will go.
- Thank you again for choosing our GenomeSurvey(TM) package I am happy to have served you and I hope that you feel more empowered about your own health. Be well.

I go home feeling a bit cheated but obviously happy of having no serious disorder in the horizon. I rush to my home computer to read the prescription that will help me prevent my heart condition and Alzeimers. I click the GoolgeDoctor(TM) button and a clip like avatar jumps around in the screen. A computerized voice reads aloud the text appearing in the screen:

Dear Pedro. You can call me clipy ! I will be your assistant for any of your health needs. In order to decrease the likelihood for the negative phenotypes associated to your genome please consider abiding by the following rules:
- Do a lot of exercise
- Eat a healthy diet
- Find balance in your life

*in an imaginary present*

- Snap out of it, what does your say ?
I look back to the small piece of paper in my hand and read:
- "You must find balance in your life", thats what it says.
- Well, these things are never wrong.

I drop the paper on my dish and finish eating the fortune cookie before leaving the chinese restaurant with my friends.
- You won't believe what I thought of ...

Further reading
The Future of Personal Genomics (21 September 2007 Science)
How much information is there really in personal genomes and how much should patients know ? Extra points for citing a post from Eye on Dna in a Science Policy Forum.
The Science and Business of Genetic Ancestry Testing (10th October 2007 Science)
A discussion surrounding results of genetic ancestry tests and the commercialization of these tests.
Google Says Its Health Platform Is Due In Early 2008 (17 October InformationWeek)
Google is still trying to build a platform to host the health related information. Microsoft already launched a service called HealthVault (read about it from Deepak).
BMC Medical Genomics (17 October BMC blog)
BMC will launch a journal dedicated to Medical Genomics, covering articles on "on functional genomics, genome structure, genome-scale population genetics, epigenomics, proteomics, systems analysis and pharmacogenomics in relation to human health and disease."
Do-it-yourself science (17 October Nature)
This editorial links up several news, opinions and articles in the last issue of Nature to ask the question - How much involvement can patient advocates have in genetics? The most impressive articles is the story of Hugh Rienhoff, a trained geneticist and biotechnology that decided to personally research about his daughter's disease (as in buying a PCR machine etc). (via Keith)
Common sense for our genomes (18 October Nature)
Steven E. Brenner explains the need for a Genome Commons. See discussion at bbgm.

Thursday, October 11, 2007

JournalFire


A new science related service called JournalFire has started. It was apparently created by a group of graduate students that are "frustrated with the current system of scientific discourse and publication". According to the initial blog post this service "provides a centralized location for you to share, discuss, and evaluate published journal articles. You, the scientists, are put in charge of determining what studies are significant and noteworthy."

I did not have a chance to test it since it is in private beta but I have asked for an account. It looks like anyone with an .edu account should be able to access it already. It sounds promising but has many of these services a lot depends on the capacity to attract a sufficiently large group of people to sustain interesting discussions. I will update the post if I get an account to test the service.
(I wonder if the people from OpenWetWare have anything to do with this)

Monday, October 01, 2007

Bio::Blogs #15

Welcome to the 15th edition of the bioinformatics blog journal Bio::Blogs.

I complained a while ago that there was very little expansion of the bioinformatics blogging community but at least in the last couple of months it looks like this is changing. Although not necessary started last month here are three blogs that I only recently noticed: At the end of the day from Stephen Spiro (Spiro lab homepage), Paradoxus and Saaien Tist from Jan Aerts.

Not only are there more blogs there are many more examples of bloggers posting original ideas and research. Most people agree that being open about research should foster collaboration but so far few people have really tried to do it. It is inspiring to read trough these examples and trying to imagine how we might be doing science in the next couple of years.
This month was also marked by the many conference reports that we had available to read and by the experiments of taking real life conferences into Second Life.

Keeping this short and to the point this edition of Bio::Blogs focuses on these conference reports and on the ongoing experiments of using blogs to post about original research. I hope this nudges more people to go ahead and give blogging and open science a try.

Conference Reports

Neil Saunders was at the ComBio2007 conference and posted his notes about it in a four part series (1,2,3,4).

Allyson from Systems Biology & Bioinformatics provided a very extensive coverage of Integrative Bioinformatics 2007. Read all about it in chronological order from parts 1 to 10 (1,2,3,4,5,6,7,8,9,10).

From my blog here are two blog posts on the FEBS workshop - "The Biology of Modular Protein Domains" (1,2). This was not really about bioinformatics but I hope it will be interesting from the perspective of what data is coming that requires good integration strategies.

I'll jump know from real life to virtual talks. Those creative people at Nature keep testing out the potential of the web to improve interchange of knowledge. They kicked-off a seminar series of digital talks in the Second Nature island withind Second Life. The first talk by Philipp Holliger, entitled "New polymerases for old DNA" was about the engineering of new polymerases to amplify ancient DNA. Joanna Scott (working at Nature) has a very nice report on the talk in her blog.

Continuing on with virtual talks, in the past month there were another 3 sessions of the series SciFoo Lives On, organized by Jean-Claude Bradley and hosted also in Second Nature. JC Bradley covered the sessions on his blog: Sept 4 - Definitions in Open Science,Sept 10 - Communicating Science with Video, Sept 24 - Open Notebook Science Case Studies. Additional coverage by other bloggers can be found via the wiki page.

Blog articles

What are some of the most frustrating bottlenecks in bioinformatics research ? Where do we really spend most of our time ? Given that we work with digitized information it should in principle be mostly about the ideas. Thinking about interesting questions, crossing information and interpreting the results. At least for me this is typically not the case. What usually takes time is gathering all the necessary information in a way that can be analyzed. Three blog posts this month discuss this problem. Hari Jayaram and Neil Saunders posted about the problems they faced when attempting to do conceptually simple tasks. In response Deepak wrote a thoughtful post on how science databases should focus also on making the information easily accessible via appropriate APIs.

From online discussions to great examples of open science we start off with Jeremiah Faith's post were he describes an idea to determine the effect of sequence level mutations on transcription, translation, and noise.

Michael Barton from Bioinformatics Zen created a new blog dedicated to posting about his research on gene expression in yeast. Jump over there to read the many blog posts that he has already there, to provide feedback and maybe find common ground for collaborations.

Also this month, RPM from Evolgen re-started his attempt to publish original research on the blog. He is trying to study the evolution of a duplicated gene in Drosophila. There are two posts covering the introduction to the problem (part 1, part 2).

The last post highlighted in this month's edition is from Benjamin M Good. He has been working on a tool called Entity Describer to add semantic controlled vocabularies to Connotea and he has posted the manuscript they will try to publish on his blog and in Nature Precedings (10101/npre.2007.945.2).

This is it for this month. As usual, if anyone is interesting in serving as editor for any future edition, tell me by email.

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 ?

Saturday, September 29, 2007

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.
Bio::Blogs #15 - call for submission

Since there were no volunteers :) I will be hosting the 15th edition of Bio::Blogs here in the blog. I will be gathering some posts from around the web on bioinformatics and other science related topics from the last month and will post about in on the 1st of October. Suggestions are more than welcome. Please email any links to interesting blog posts to bioblogs at gmail dot com.

On a personal note, I have defended my PhD :). This mostly explains the low volume blogging.
The ephemeral journal II

(via Deepak) Earlier this month I posted about how re-grouping of content after publication could be used to foster the creation of more focused online scientific communities. My impression is that these "places" could more easily attract a group of people of similar interests that would more likely engage in discussions, in contrast to a place like PLoS ONE that covers way to many topics.

There are several names for these groupings (Nature/BMC gateways, Nature Reports, a topics page) and PLoS came out with another one - Hub. They launched a re-grouping of content focused on Clinical Trials that they call PLoS Hub for Clinical Trials. It is built on Topaz so it has everything that PLoS ONE has (comments, ratings, trackbacks,etc).

They mention in the home page of this Hub that they plan to in the future also "feature open-access articles from other journals plus user-generated content". I suspect that they could go even a bit further on this and give more control to the users for the creation of content for the Hubs and even to create new Hubs. One thing that I like in traditional journals that also creates a feeling of identity and community is the more personal news and views and editorials. PLoS could commission/invite scientists/bloggers to help create this type of content for their Hubs. This would be something like a community blog centered on this Hubs' research.

Once upon a time (before Digg if I remember right), we tried to do this in Nodalpoint. For a while we had a queue from bioinformatic related journals that we could vote on to upgrade it to the front page of the blog. At the time it did not work very well because of lack of users and participation but it in essence it was not very different from what the publishers are trying to do now. Maybe we could try it again :).

Wednesday, September 19, 2007

Vote for your favorite life science blogs

(via Science Hacker and Postgenomic) The Scientist wants to compile a list of life science blogs that people enjoy reading as a reference. It is really not a good question to ask since there are so many different fields and styles of writing.

Tuesday, September 18, 2007

More on open science

I am still catching up with a backlog of feeds and e-tocs but I just noticed that Benjamin Good posted his manuscript on E.D. in Nature Precedings. I wend back to his post where he first presented the manuscript to have a look at the comments and there is a nice discussion going on there. It is a good example of the usefulness of posting our work online. There might be still few people knowledgeable about particular interests to gain very good feedback in all areas but this will tend to grow with time.

Michael Barton from Bioinformatics Zen started a new blog to use as an open science notebook about his own research.

I have a mini project in mind about the evolution of domain families that I will start describing and working on here in the blog soon.

Sunday, September 09, 2007

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.

Saturday, September 08, 2007

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.

Tuesday, September 04, 2007

Scifoo Lives On: Definitions in Open Science

I am having a quick look at the session Definition in Open Science, going on in Second Nature (I'm Duriel Akula in Second Life). The place looks very different from the first time I had a look around the island. It is full of posters and other interesting material. Here is a picture as some of the first people started gathering:


Live coverage of the event by Berci (also in the picture).

Wednesday, August 29, 2007

Bio::Blogs #14 - Update

The 14th edition of Bio::Blogs will be hosted by Ricardo at My Biotech Life. It will be made available on the 1st of September and submissions can be sent by email as mentioned in his blog post.

Update: The 14th edition is now posted at My Biotech Life. With all the deadlines I had this past month I left it almost until the end to organize a host. Thanks again to everyone that contributed on such short notice.

Is anyone interested in serving as host for the October edition ?
SciVee.tv background info

A while ago SciVee was announced via several blog posts. Here is a link to the first one I read by Deepak and a link to the cluster in Postgenomic.

I thought at first glance that this was a partnership between some small start-up and a content provider (PLoS). After browsing a couple of the videos I noticed that most are from papers authored by Philip E. Bourne. Given the connections to both PLoS and SDSC (two of the site's partners) I thought that this might be an academic effort after all.
A couple of searches tells us that abailey was responsible for a Scivee mailing list at SDCS that no longer exists. abailey apparently stands for Apryl Bailey, someone involved in the SDSC CI Channel, a "webcast video service and resource for the scientific communities" (from their about page).

Apryl Bailey also appears listed in the Scivee Team in one of the slides of a talk (PDF) that Philip Bourne gave in June this year. According to this recent news story it looks like the launch was actually premature and triggered by this talk:
"According to one founder, Philip Bourne of the University of California–San Diego (UCSD) and founding editor in chief of PLoS Computational Biology, he talked about the project at a scientific meeting and the buzz began prematurely."

It is an academic effort, probably related to this CI Channel mentioned above:
"The project began with some pilot pubcasts done at UCSD to test video formats and has involved the other PLoS editors. There are currently eight people on the SciVee team. The SDSC is providing the site hosting."

From one of the slides of the talk:
Developmental Phases
• Phase I (One Year) – Invite authors of papers published in PLoS journals to upload a video or podcast to SciVee.tv describing the motivation, key results and major conclusions of the published study. Establish linkage between literature and video – source of metadata etc. – September 2007

• Phase II (Years 2- 3) - Scrape PubMed on a daily basis and extend the invitation to authors of all papers in the life sciences; develop video authoring server; provide
ratings and virtual community comment

• Phase III (Year 4- ) - Extend to other scientific disciplines

Saturday, August 11, 2007

The ephemeral journal

Recently I mentioned the start of yet another journal covering one of the topics I would place on the top of a hype cycle curve. This together with the apparent ever increasing number of journals everywhere got me thinking of birth/death of science journals. The cost of starting up a new journal is so low that the turn-over can only be higher. Still, we don't typically see a lot of "journal death". They are meant to be respected and built up reputation among the public audience they serve.
It looks however inevitable that with a limited attention capacity and ever increasing number of journals that science hype cycles might have a strong influence on a journals activities. If hyped up subjects sprout out new journals quickly (i.e stem cells, systems biology, synthetic biology), underperforming science memes will suffer from lack of attention. If I had a biomedical related science publishing house I would probably be thinking of launching a journal to cover metagenomics and another to cover personalized medicine.

Creating and destroying journals based on hype cycles sounds a bit exaggerated but at least there is no reason to think that a journal is here to stay. This can also happen via in a more subtle way, trough re-grouping of content after publication. Call it a gateway, a report, a topics page,a portal (harder to find), the idea is there are several ways one can group published papers to serve a target audience. Digital works are not things, they can be in several places and we can slice and dice the views as we wish. One great thing about these views is that they are more likely to attract discussion since there is more likely a group of people around with similar interests. This would be even more so if the users had some power to control the content. Nature Reports allow users to submit papers and to vote on them but it is still too soon to tell if discussions in topic pages are more frequent than on a site like PLoS ONE.

Instead of subscribing to the high impact journals, and lower impact journals of our topics of interest, we would state our interests in the views/portals/gateways we select to participate in and hopefully the works would be distributed to target audiences as fitting. Things that are of very high perceived impact would be cross-posted to many more views than more specific works. The value could still be perceived either pre or post publication.

The main advantage for the publisher is many more pages with well targeted audiences. Some of these views could even be of interest to a very wide non scientific audience. All of these should improve advertisement revenue.
Quotes

Another interesting SciView interview is available at Blind.Scientist. Here is one quote from Alexei Drummond (Chief Scientist of Biomatters) that I liked:

"I think that bioinformatics has to become a field where people without programming skills can contribute substantially. I would argue that all of the programmers in bioinformatics should be working very hard to program themselves out of their jobs (and into more satisfying jobs)."


Science advances quickly and so do the computational needs. Can we ever do away with these one off scripts if there are always new data types and innovative ways of analyzing them ? I guess the ideas around workflows and such could lead to very visual oriented programing that anyone can do.

Thursday, August 09, 2007

First issue of IET Synthetic Biology

The first issue of (yet) another journal related to systems&synthetic biology is now online. IET Synthetic Biology will be freely available during this year. This issue covers several works from iGEM and the editorial is worth a read to have a look at the future direction of the journal.

In addition to conventional research and review articles, we see an important need for practical articles describing technical advances and innovative methods useful in synthetic biology. We will encourage submission of technical articles that might describe novel BioBrick components, construction techniques, characterisation of a new biological circuit, new software or a practical ‘hands-on’ guide to the construction of new instrumentation or a biological device.

In addition to the print journal, we are developing associated web resources. These will include a repository of online video resources, specialised review material and research tools for synthetic biology.


Some journals tracking similar fields:
Molecular Systems Biology
BMC Systems Biology
Systems and Synthetic Biology
HSFP Journal
IET Systems Biology

Tuesday, August 07, 2007

TwoThree new bioinformatic related blogs

A quick post to link out to two new bioinformatic related blogs:

Freelancing science (by Paweł Szczęsny)
Open.nfo (by Keith)

I will be happy the day there are too many to track :).

Updated: It could the official month of "start your own bioinformatics blog". The bio.struct blog is the third one so far.

Saturday, August 04, 2007

SciFoo starts ...

and I am not there :). No fun ! The Science Foo Camp 2007 has started at Googleplex and there is already some blog coverage. To have a look at what is going on at camp here is a tip from Andrew Walkingshaw:

* http://www.lexical.org.uk/planetscifoo/ - participants’ blogs
* http://flickr.com/photos/tags/scifoo/ - photos
* http://www.technorati.com/tags/scifoo/ - general blogosphere commentary

There is also some live Twitter feeds from Deepak and Nat Torkington.

To start off go have a look at pictures posted by Bora, you might recognize one or two of these bloggers.

Maybe next year we can try to organize a Science Barcamp :) Why should they have all the fun.

Friday, August 03, 2007

Bio::Blogs#13

A great edition of the monthly Bio::Blogs is up at Neil's blog. This month there are plenty of tutorials and a round up of blog coverage about the ISMB/ECCB 2007 conference.

PDF version for offline reading of the editorial and highlighted posts is here and here (Box.net copy).

If someone wants to give it a try at editing future editions of Bio::Blogs let me know.

Speaking of community projects, the list of webservers published in that last NAR webserver edition are in this Nodalpoint wiki webpage. If you try one of these services spend a minute noting down if it was even available, if it worked well, etc.

Wednesday, August 01, 2007

Microattribution

(via Peter Suber) An editorial in Nature Genetics discusses the need to establish microatribution systems:
"When requiring authors to deposit data in public databases, journals, databases and funders should ensure that quantitative credit for the use of every data entry will accrue to the relevant members of the data-producing and annotating teams. In an era in which consortia are producing more (and more useful) papers than individuals and small groups, the careers of individuals are as much in need of specific credit as those of the scientific visionaries and wranglers who hold the consortia together."

This sounds great. From the journals point of view this would mean "encouraging" the authors to link to all resources used. This information would then need to be aggregated and made available to everyone. This and other measures would help to change the current credit system that tends to reward researchers for producing papers in high impact factor journals (that does not correlate with individual paper citations) instead of rewarding scientists for the usefulness of their research.

Sunday, July 29, 2007

Bio::Blogs #13 call for submissions

Neil has kindly agreed to host the next edition of Bio::Blogs, due out on the first of August. Send in links to blog posts of bioinformatics/chemioinformatics/omics/open science related content to bioblogs at gmail and they will be re-directed to him.

Friday, July 27, 2007

Trade books vs Nature publishing

(via Richard Charkin blog) Richard Charkin is the Chief Executive of Macmillan (Nature Publishing is a subsidiary of Macmillan). He posted his thoughts on digital books are not as successful as the digital publishing going on at Nature.

I can't help noticing the second reason (my emphasis):
2. Scientific publishing has been intrinsically more profitable than trade book publishing. This allowed the major publishers and societies to invest the significant sums needed to create electronic delivery and storage platforms for scientific information. These platforms are a cornerstone for the creation of a new business and communication model.

and read it as "higher profit margins".
Google code for educators

(via the Google Blog) Google started a website to gather teaching materials for CS educators, covering some of the most recent technologies. Right now it has some material for AJAX Programming, Distributed Systems and Web Security. There are some video lectures and presentations. There is already some material on parallel programming (mostly related to their MapReduce) that should be of use to bioinformatics.

One a related topic Tiago has on his blog started a multipart series about "Bioinformatics, multi-core CPUs and grid computing". The first and second part are already available.

Tuesday, July 24, 2007

Slideshare adds voice

(via TechCrunch) Slideshare, a site to share presentations online has added voice synchronization. We can now provide a link to an mp3 file and Slideshare provides with some tools to sync the audio to the slides, such that each slide is linked to part of the audio track. More information and examples can be found in this FAQ page.

In related news, Bioscreencast has now a group in Facebook.

Saturday, July 14, 2007

Another Open lab book

(Via Open Reading Frame) Jeremiah Faith is given open notebook science a try and compiling some tips. He joins Rosie Redfield (microbiology) and Jean-Claude Bradley (chemistry) in exposing most of their research online and leading the way to changing the mindset towards open science.

Jeremiah Faith also has an interesting idea about using conference money to pay for advertisement. He figures that well targeted ads can get you more attention than a talk. He like the idea because it is thinking out of box but I think that the type of connection that one can create on a conference with other people is not so easy to recreate online. Also, there might not be any need to spend money on advertisement if the blogs keeps on topic and is interesting enough to get incoming links. The blog can be a good personal marketing tool.

Friday, July 13, 2007

Early response to PLoS ratings

PLoS ONE pushed out a rating systems in the latest update of their website. I though it was another quiet update but several announcements are now up.

The technical details were described by Richard Cave and Chris Surridge invites everyone to "Rate Early, Rate Often". Bora (that now works for PLoS) summed it up in a blog post as well.

And just because they make it so easy to query the data, here goes the stats 3 days after the announcement:
Number of papers queried: 611
Number of papers rated: 47
Number of ratings: 50
Ratings: Average - 75%; Max - 100%; Min - 40%

Top rated papers (all with 100%)
10.1371/journal.pone.0000288 (rated by: brembs)
10.1371/journal.pone.0000354 (rated by: brembs)
10.1371/journal.pone.0000439 (rated by: brembs)
10.1371/journal.pone.0000349 (rated by: Complexity_Group)
10.1371/journal.pone.0000351 (rated by: crusio)
10.1371/journal.pone.0000455 (rated by: crusio)
10.1371/journal.pone.0000123 (rated by: Damien)
10.1371/journal.pone.0000224 (rated by: Damien)

Maybe in the long run it would be nice to know if the user that rated is also an author in the paper :), or put a comment in the ratings suggesting that authors are not very good at evaluating their own work.

Number of users that have rated: 24
Top 3 users:
Chris_Surridge
Complexity_Group
jstajich

The lowest rating so far:
10.1371/journal.pone.0000257 (rated by:godzikc)

There is no point in trying to conclude anything from this. It was just for the fun of it. If I could make a small wish it would be have a similar way to query for the accumulated number of page views or visitors for a given DOI.

Wednesday, July 11, 2007

Open-source architecture to house the world

Here is a very energetic talk (filmed in February 2006) by Cameron Sinclair hosted at TED talks. He is part of the Architecture for Humanity organization that promotes architectural and design solutions to global, social and humanitarian crises. A very inspiring example of how internet really makes the world small and how ideas like crowdsourcing and the open access to innovation can make a difference. The first time I heard about a creative commons house design.

They have started a project called Open Architecture Network to serve as hub for collaborative efforts.

Tuesday, July 10, 2007

What is the $value$ of an editorial decision ?

(warning: random thoughts ahead)

From my viewpoint open access is doing great. PLoS has demonstrated that authors want to publish in open access journals and that these journals can quickly establish themselves as high impact forums for their respective audiences. BMC is set to show that open access can be profitable and within BMC some journals are are also trying to position themselves in the top tier of perceived impact.

How will BMC manage this and will PLoS and others find a way to serve the authors interest while keeping the direct costs to the authors within reasonable ranges (even if they are paid by the funding bodies) ? I can't really answer this :) but I do note a trend. Open access publishers like PLoS and BMC are increasingly publishing more and decreasing the rejection rates (when considering all that is published within the brand).

BMC has primarily focused on publishing high volume (peer-reviewed) articles without regarding to much on perceived impact in the field. I might be incorrect but more recently they have been trying to highlight a group of flagship journals (BMC Biology, Genome Biology and Journal of Biology) where they filter on perceived impact. They have even said that papers submitted to other BMC journals can even be suggested "up" if they are found to be of high impact.

PLoS on the other hand had the the exact opposite direction. PLoS started with their flagship journals (PLoS Biology and later PLoS Medicine), then created the community journals (PLoS Genetics, Computational Biology and Pathogens) and now opened PLoS ONE that will not filter on perceived impact.

On an author pays model, the most obvious way to limit the cost per paper and still provide a solid evaluation of perceived impact, is to have journals that cover the broad spectrum of perceived impact. In this way, for the publisher, the overall rejection rates decrease, the papers are evaluated and directed to the appropriate "level" of perceived impact.

Also, on closed publishers it is custom to be able to transition a manuscript with the peer-review comments from one journal to another of the same publisher. This practice is can be advantageous to everyone. saving the time of the another peer-review process.

Taking away the costs of editing and printing (online this can be very small) most of the costs of sustaining a science journal should mainly come from the editorial staff. So, what is the value of an editorial decision ? In other words, could there be freelance editors ? Could the editors be separated from the publisher ? Imagine I read a paper from a pre-print server, ask some people to peer-review (why would they?) and sell our evaluation to a journal.

Also, can a publisher sell the editorial decision to another publisher ? Lets imagine a journal that has a very high rejection rate, the editor asks referees for comments but ultimately the manuscript is rejected. The editor could then ask the authors where they want to send it next and offer to provide the referee report and editorial comments directly to the next journal to expedite the process. Could this journal get paid for this ?

Monday, July 09, 2007

User ratings in PLoS ONE

Another quiet update on the PLoS ONE interface. They have introduced an interface for user ratings. The overall rating can be seen in the right bar (when reading a paper on the site) and expanded to show a dissection into 3 categories: insight, reliability and style.

A click pops up a voting screen:



The nice detail is that we can query rating data by DOI. (example). It is not really an API, but the info is there and it is easily parsable. The PLoS ONE managing director, Chris Surridge, mentioned in the PLoS Facebook page, a couple of days ago that this change would be up soon.
Filtering papers on number of downloads

I was having a look at highly accessed papers for BMC Bioinformatics. In BMC, all journals have a page with the statistics of the most highly accessed papers of the last month. Several other journals now provide a similar service. The cool think about BMC is that they even tell you how many views per paper (sum of abstract, full text and PDF accesses on BioMed Central in the last 30 days). Not only that, the information in on the RSS feed they provide. That makes it very easy to feed into a pipe and have a threshold for number of views above which it will show up on the filtered feed.

Here is pipe example to filter out BMC Bioinformatic papers below 1000 views. The only problem is that the information is not stored as a number (example :"Number of accesses: 1226"). That is why I used a regular expression [1-9][0-9][0-9][0-9]$ instead of number filtering. I also don't know if the numbers are updated everyday .. but I hope so.

Even better would be to have some kind of service that given a DOI BMC would provide exactly this information structure. If other repositories provide a similar service then there is no point in worrying about the dilution in the number of page views because of open access because we could just sum views in the publishers site with Pubmed Central, etc.
Metadata infrastructure

Deepak and Neil blogged today about tagging and adding more structured metadata to the science web. I started by commenting to Deepak's post but it grew a bit so I changed it to a blog post.

The most obvious start for me would be to find a standard to communicate information on the perceived impact of a paper (extending hReview for example). It has a unique digital identifier and ways to resolve it but no way to communicate number of downloads at publisher site X, number of incoming citations in other papers, in blog posts, simple rating by users.

On the user side the blogging platforms, social network sites and wikis would need some way to add microformat support. See for example this plugin for wordpress (via F&L). If someone knows how to do the same for blogger please tell me in the comments. It needs to be something like clicking a button to link to a paper and out comes a formated hReview.

I think finding standards for manuscripts is a good start because a lot of people already tag and blog about papers. There is a lot of information to aggregate and a lot of interest in having a good measure of impact for individual papers. What we learn from putting this in place can later be used for other types of data communication (e-lab books). Another possible good start would be conferences and conference reports (related to hCalendar ?).

Of course, this would require the participation of science publishers. They are the ones best in place to set up the tools and expose some of the information in a structured way to help enforce a standard.

Saturday, July 07, 2007

Referee reports in Nature Precedings ?

I was having a look at some of the bioinformatics manuscripts available in Precedings and I come upon this paper on "The Reproducibility of Lists of Differentially Expressed Genes in Microarray Studies". After the figures there is a letter to the editor with the response to the questions from the referees.

I could not find the paper published in a peer-reviewed journal and I wonder if this was intentional of maybe part of an (opt-in and maybe buggy) automatic procedure from Nature to have submitted papers appear in Precedings. If I was an editor of a bioinformatics/genomics journal I could now consider if this paper with these referee reports would be interesting to the journal and send an email to authors suggesting that if by some chance their paper gets reject my journal would be willing to publish it.

Deepak was recently saying that it would be good to have access to this type of information. Why was a paper rejected from some journal and published in another? Most manuscripts go through several editorial and referee evaluations before getting published. Biology Direct and now PLoS ONE (too some extent) capture this information. I have found that many times it is useful to read the referee comments in Biology Direct because it provides with several independent criticism that makes it easier to home in on good and bad parts of the work.

I am sure that this has come up before in the context of ArXive but wouldn't it be more efficient to have journal editors somehow fish out from a common pool what is more interesting and hight impact to their community instead of the current submission ladder that i assume a lot of people go through ? We would submit to a preprint server and tag the paper according to perceived audience (i.e cell biology, bioinformatics, etc). Editors would flag their interest for the paper and the authors would select one of the journals. You can imagine some of the dynamics that this could create with some journals only looking at manuscripts that have already been flagged by some other journals, etc.

The referee reports would be attached the paper and the editor would make a decision. If rejected the paper would be up again for editorial selection but with the previous information attached. Other journals could just decide to publish with those referee comments.

I think this is not far from what already happens within publishing houses. Referee reports can be passed around to other journals of the same publisher. This would make it more general. Although there are clear advantages to authors (fewer rounds of refereeing and quicker publishing), it would be hard to convince most publishers to such a scheme. For those publishing mostly journals with low rejection rates it would be beneficial since most likely the papers have been already refereed, but for those with high rejection rates it could feel like they would be giving away their work for free. Since it is really the work of the referees maybe it should be up to the referees to decide if the reports can be made public or not, period.

Wednesday, July 04, 2007

RSS feed for BiomedCentral comments

As if there is not enough things to read this days I though it would be interesting to provide an RSS feed for BiomedCentral comments. I tried to use openkapow to scrape the information from the webpage but for some reason the feed only worked a couple of times after being published. Instead I used Dapper that amazingly enough produced a more stable feed. The full, unfiltered feed can be found here.

The feed includes the title (with a URL to the comment page, where there is a DOI to the cited paper), the short description provided in the main webpage and the journal (saved in the date). The feed can be filtered for particular journals using this simple pipe from Yahoo pipes that is currently set for BMC Genomics or BMC Bioinformatics.

Sunday, July 01, 2007

BioBlogs #12 and a blogroll update

The 12th edition of Bio::Blogs is out in Nodalpoint. It has been one year of monthly posts (mostly) about bioinformatics. Is anyone interested in hosting the next edition ?

Also, I updated my blogroll to reflect more what I am currently reading. Most updates are in the bioinformatics part but there are a couple of additions in all of them.
Bioscreencast and Multimedia@Harvard

Deepak and Harijay have posted about Bioscreencast, a project they were involved with. It is a repository for science related screencast. A screencast is video capturing the output of your screen usually with some audio narration to explain to the viewer what
it is being shown. They hope it will be used by scientists to share knowledge on how to use science related computer tools.

On a related note Ricardo posted a nice review on multimedia sites for science. He linked to this amazing video of the inner working of the cell:


You can see the full (narrated) version of this movie along with other science media files in this Multimedia Production Site at Harvard.

Wednesday, June 27, 2007

Call for Bio::Blogs #12

I am collecting submissions for the 12th edition of Bio::Blogs. Send in links to blog posts you want to share from your blog or that you enjoyed reading in other blogs to bioblogs at gmail until the end of the month. The next edition will be up at Nodalpoint on the 1st of Jully.

Maybe it could be cool to try out a section on papers of the month as voted by everyone (Neil used to do this once in a while). Anyone interested in participating just has to send a link to a paper, published last month and related to bioinformatics, with a short paragraph explaining what is nice about the paper.

Mike over at Bioinformatics Zen is asking how to continue the Tips and Tricks section of Bio::Blogs. He has put up a wiki page on open science in Nodalpoint to collect information for a possible future edition of the special section.

Monday, June 25, 2007

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)

Thursday, June 21, 2007

Structures in Systems Biology (a double bill)

Once in a while I get to write about what I have been working on. The last time it was about the evolution of protein interaction networks. This time it is about two papers that I contributed too. A review about the use of structures in systems biology and an article about structure based prediction of Ras/RBD interactions. I am sorry to say that both require a subscription (pedrobeltrao *at* gmail).

Main conclusions
Structural data can be used to predict Ras/RBD interactions with approximately 80% accuracy
We can and should use structural information to understand the main molecular properties before abstracting away the atomic details. Structural genomics can serve as a bridge between the abstract network view and the atomic detail.

The Making off
Although I am not the first author of the article I think it is safe to say that the main inspiration for the line of work done by Kiel (see also previous publication) is the work by Aloy and Russell where they first showed that it was possible to use a protein complex to predict if similar proteins would be able to interact in a similar way. What Kiel showed is that more accurate predictions can be made by modeling the protein domains under test onto the complex and evaluating the binding energy using a protein design program under development in the lab (FoldX). She used pull-down experiments and available information on Ras/RBD interactions to benchmark the predictions.

The predicted binding energies inform us about the probability that the two protein domains would bind in vitro. Inside the cell there are many other factors contributing to the likelihood of binding (gene expression, localization, complex formation, post-translational modifications, etc). To try to add some of this knowledge to the predictions I contributed with a Naive Bayes predictor that combines information on gene expression, GO functions, conserved physical/genetic interactions in other species and shared binding partners. The likelihood score obtained can be used to further rank the predicted interactions according to the likelihood that these are occurring inside the cell. In supplementary information there are the methods and tables with individual likelihood scores that can be used to reproduce the Naive Bayes predictor.

From atoms to nodes and edges
I think one of the main goals of the the review was to show the current progress that has been made in using structural information to obtain the fundamental properties (binding sites, catalytic sites, protein dynamics, etc) of cellular components that may allow us to create models of cellular functions. There has been some work in approximating the very abstract "nodes and edges" view of cellular interactions to a more traditional pathway model. This has been done typically by searching for modules and particular node roles that depend on the patterns of intra or inter module interactions (see Guimera et al). We should be able to automatically decorate interaction networks (and the pathway modules) with structural data that can further help to computationally generate meaningful models of cellular functions.
The picture was obtained from Beltrao et al , it is Copyright © 2007 Elsevier Ltd and it used here hopefully under fair use.

In the pipeline
There are several important details to iron out before we can just apply this structure based prediction of protein interactions to any protein that we can model onto complexes. We are in the process of testing the approach with other different domain types. Some of if I have been more directly involved and we started now the submission process. I tried to get everyone to agree to submit it to a preprint server but not everyone was comfortable with the idea.

Thursday, June 07, 2007

Tangled Bank #81 is know available

I participated with a submission to the latest edition of Tangled Bank (the first science carnival blog journal around) that is available at the Behavioral Ecology Blog. Thanks to RPM at Evolgen for "peer-reviewing" my post on protein evolution :).
Nature Precedings, a pre-print server for biomedical research

It was hard to hold off from blogging about this but I can finally write about Nature Precedings, a new free service provided by the Nature Publishing Group. The official announcement is in this editorial:
"... this site will enable researchers to share, discuss and cite their early findings. It provides a lightly moderated and relatively informal channel for scientists to disseminate information, especially recent experimental results and emerging conclusions."
"...the site will host a wide range of research documents, including preprints, unpublished manuscripts, white papers, technical papers, supplementary findings, posters and presentations."


I have been participating in the beta for some months now and as it is mentioned in the editorial it will be openly available starting next week. All documents are citable (have DOIs), are not peer-reviewed (in the formal sense) and are archived under a creative commons license (derivatives allowed). The site has the community features (tagging/commenting/rating/RSS feeds) that you would expect and that will hopefully allow for requesting and providing comments on early findings. In summary an nicer version of ArXive for biomedical research.

I think this is great news that serves on one hand to improve access to research (open access by pre-print archiving) and increase the openness of research. This can provide a place for independent time-stamping of early findings and could be improved (hopefully with community feedback) until it is appropriate for formal submission to a peer-reviewed journal.

A framework for open science (in biology) can now go from blogs/wikis to pre-print server to peer-reviewed journals. Many ideas might die along the way and many collaborations might form by connecting early findings in an unexpected way.

Of course if you are in maths/physics you have arXive and you are probably wondering what is taking us biomedical researchers so long to get into this.

Friday, June 01, 2007

Bio::Blogs# 11

The 11th edition of Bio::Blogs, is online at Nodalpoint. We tried to do something different this time. Michael Barton volunteered to host a special section dedicated to tips and tricks for bioinformatics that is hosted separately in Bioinformatics Zen. Because there were so many posts this month about personalized medicine there is also a special section on that.

There are three separate PDFs for this edition: 1) the main PDF can be found here; 2) The one on personalized medicine can be downloaded here; the one for tips and tricks available from Bioinformatics Zen. Michael did a great job with this special section, with a very cool design.