In silico network reconstruction

It is day one of Just Science week and I want to tell you about a recent paper that was published in BMC Systems Biology by Rui Alves and Albert Sorribas. It is about a general approach to integrate information to come up with models for cellular pathways. What does this mean and why is this important ?

Increasingly the scientific knowledge is being stored in databases (literature, protein structures, gene expression, protein-protein interactions, protein-DNA interactions, etc). The general idea behind the work described is that we should be able to use the accumulated information about cellular pathways to extract models of how the cell's components interact to preform their functions. By models I mean a formal representation that can tell us how the components' concentrations and activities change with time.

There are several works already dealing with this problem of trying to reconstruct cellular networks from large data sources but I found this article particularly interesting because it uses so many of these methods.

To give you an idea I reproduce below figure 4 of the paper with a diagram of the method (click to zoom in):




The authors have pulled in experimentally known interactions and combined them with putative interactions obtained from docking and phylogenetic based predictions. These predicted networks are then converted to several possible mathematical models that are examined under different parameter conditions and compared with known experimental values.

This method should be particularly suited for a case when some of the genes in the pathway are known and there are experimental measured outputs for the pathway that can be compared with the predictions from the putative pathway models.

Ideally this whole procedure would be fully converted into an automatic pipeline that could be used by people that are not so familiar with the tools.

I will try to stick with the same theme during the week, hopefully covering different methods to achieve the same thing.

Publishing greasemonkey scripts (update)

A while ago I asked if greasemonkey scripts should be published in peer reviewed journals or if blogs could be a more suitable way of distributing these tools. The blog post was triggered by the publication of iHOPerator, mentioned also by Deepak.

I would like to thank one of the authors, Benjamin Good, and a BMC editor, Matt Hodgkinson, for taking the time to post their opinion in the comments. In summary they both argue that this publication helps raise awareness to greasemonkey and related technologies.

For me this exchange in the comments exemplifies the usefulness of the web for discussing science. The comments on this paper are aggregated in this Postgenomic entry and anyone could, in principle, participate no matter where they are.

This also reminded me of a discussion I had with someone here at EMBL recently. If web based discussions like this take off then authors might have a higher work load in trying to keep up with what is being said about their works. If a misinterpretation occurs it has a higher potential for spreading online. On the other hand, these sorts of web discussion help to level the playing field for manuscripts. In the near future it might not matter so much were the paper is published but if attracted the attention of the people in the field.

Just Science

(Via RPM, Razib, Chris, Arunn) Next week is Just Science week. I will try to review recent papers on cellular networks, systems/synthetic biology and evolution that I found interesting.

Bio::Blogs #7

The February edition of Bio::Blogs was just published in BioHacking. Thanks to Paras for editing it. He highlighted some blogs related to synthetic biology and some of the recent bioinformatics posts from Neil, Sandra and Pierre.

The 8th edition will be coming back here. The participation has been generally going down so Bio::Blogs might, in the near future, morph to something else.
Just to give it a little twist I thought that it could be interesting to add a PDF version of Bio::Blogs (with the permission of the authors of course). So, for the next month entries I will be asking if the authors concede that the blog posts be compiled into a printable document.

Entries can be submitted until the end of February to bioblogs at gmail.

Bio::Blogs #7 final call



As Deepak mentioned in his blog, the February edition of Bio::Blogs (the bioinformatics blog journal) is due soon. It will be up on the 2nd of February at BioHacking, so get your blogging pens working. It has been 2 months since the last call. Go have a look at the past two months, pick up one of your posts or a post you liked, related to bioinformatics and send it to the usual bioblogs at gmail.

The 8th edition will be back here on this blog. If anyone is interested in hosting future editions let me know in the comments or by email and I can make a list (including previous editors :).

Let's see how many posts highlighted in Bio::Blogs make it to the next years Science Blogging Anthology ;).

Not so silent mutations


DNA mutations that do not change the coding amino-acid are many times referred to as "silent mutations", or synonymous mutations, because it is less likely that they will result in a change in function. Synonymous mutations are often considered to be evolutionary neutral and the ratio of non-synonymous substitutions (Ka) to synonymous substitutions (Ks) is used to study sequence evolution. It can be used for example to search for DNA regions targeted by selection (see review and a practical application).


In the last issue of Science Kimchi-Sarfaty and colleagues found a synonymous mutation in a transport protein that has an effect on the protein function. They have shown, at least in cell-lines, that the mutation does not affect mRNA levels nor the produced protein sequence. Finally the authors showed that the mutation might change the protein's conformation by comparing the sensibility of wild type and mutated sequence to trypsin digestion.

The authors speculate that the usage of that particular codon, even if not affecting the coding region, might change the translation rate and folding of the protein. It had already been shown in E. coli that synonymous mutations can affect the in vivo folding of a protein. Here the authors have shown a case where a silent mutation can change the substrate specificity of a transporter.

Because of these codon preferences it is important to adjust for codon selection pressures when studying synonymous substitutions. The codon preferences are usually considered to be due to differences in the pool of the cognate tRNA but other studies have shown that codon bias might arise also by codon context. In E. coli, codon pair preferences, were observed to affect their in vivo translation. Also, these codon pair preferences are species specific and are, at least in part, influenced by nucleotide positions within A-site tRNA sequences.

Hypothesis: If codon pairs can be selected due to tRNA structural constrains on the ribosome P and A sites then it might be necessary to correct for these codon preferences when studying synonymous mutations.

System Biology quick links

(via Pierre) BMC System Biology has published their first papers. More or less at the same time the new Systems and Synthetic Biology (published by Springer Netherlands) has started publishing papers. These two journals join IEE Systems Biology and Molecular Systems Biology (Nature/EMBO) as forums to publish works on Systems and Synthetic Biology. All journals (with the exception of IEE Systems Biology) publish in open access or at least (in the case of Systems and Synthetic Biology) offer an open access option.

Some of the talks from the BioSysBio conference are online in Goggle Video.

Here is a nice talk from Alfonso Valencia talking about species co-evolution and a very promising improvement to a sequence based method to predict protein-protein interactions:

Social gene annotation in Connotea

There has been a lot of excitement over the recent web technological developments. Time magazine has recognized this by announcing that instead of profiling an individual in their annual issue of Person of Year they decided to select You as the most influential group of last year. This "you" refers to everyone that is out there on the web building, interacting, blogging, uploading their videos and pictures for the world to see. As with almost every rising meme, the backlash is inevitable. Some see this web euphoria as little more than global narcissism.

This social web holds some powerful promises of more efficient collaboration but clear examples might still be lacking. Scientists, given our need to communicate and collaborate, are a group of individuals that could do more to take advantage of these tools. Unfortunately we seem to be too unaware and too slow to pick them up.

I have shown before that the accumulating body of knowledge in Connotea, in the form of simple tagging of science papers, can in principle be used to highlight papers of higher impact.

I tough that it could also be possible to mine Connotea to retrieve gene annotations. I tested if manuscripts tagged as "cell-cycle" and "yeast" would contain, in their abstracts, mostly genes names related to cell cycle in yeast. There are currently 38 papers in Connotea tagged as cell-cycle and yeast with an associated Pubmed ID. I used a dictionary of S. cerevisiae gene names obtained from SGD and retrieved the abstracts for the 38 manuscripts using eUtils.

Within these abstracts there were 38 gene names associated by a simple pattern match. To evaluate the performance of this social gene annotation I took from the SGD's slim GO mapping the function and processes associated to these genes. I also included the gene description from gene name registry.

Table 1 - Known GO process/function annotations and gene function description associated to the genes predicted to participate in cell-cycle in yeast by social annotations.

From the 38 genes, 14 (~37%) are annotated in the slim GO annotation as participating in cell-cycle,meiosis or cytokinesis. From the remaining, 15 (39%) have a described function associated to the cell-cycle (ex. G1 cyclin involved in cell cycle progression, expression restricted to mother cells in late G1 as controlled by Swi4p-Swi6p, Swi5p and Ash1p,etc). In total roughly 76% of the gene names obtained are associated to cell-cycle in S. cerevisiae.


This simple test highlights the potential usefulness of social bookmarking of science papers. However it was limited to a very specific field and to a very small number of annotated manuscripts. Hopefully someone can come up with a better way of testing this :).

Petition for guaranteed public access

(via PLoS publishing blog):
"A group of European organisations - JISC (Joint Information Systems Committee, UK), SURF (Netherlands), SPARC Europe, DFG (Deutsches Forschungsgemeinschaft, Germany), DEFF (Denmark's Electronic Research Library) - have posted a petition to encourage the EC to formally endorse the open access recommendations."

This petition recommends that "any potential 'embargo' on free access should be set at no more than six months following publication" for any EC funded research.

Have a look and sign the petition if you are for it.

Bio::Blogs# 7 and some quick links

The bioinformatics blog journal Bio::Blogs will have it's 7th edition on the 1st of February. We skipped the January edition because of the holidays. It will be hosted by Paras Chopra on BioHacking blog. Anyone can submit the link to their posts on paras1987 {at} gmail or bioblogs {at} gmail until the end of this month.

Some quick links:
Paras released the source code of a Python program for protein structure prediction.

(via Gerstein' blog) Yale university has a podcast. I wish I could convince EMBL's press office to start blogging and/or a podcast.

(via Deepak) The Science Commons blog announced that the three journals published by EMBO and NPG (EMBO reports, EMBO journal and Molecular Systems Biolgoy) will soon start publishing with a creative commons license. More information on the subject can be found in the EMBO site. In the case of Molecular Systems Biology all articles are published in open access but for EMBO Journal and EMBO reports it looks like the author will decide if they wish to pay an extra fee (2000 euros) to publish in open access. Only the articles published in open access will be published with the creative commons license. Adopting the creative commons license will make re-using their papers much easier, hopefully increasing the usefulness of their content.
(disclaimer: I am currently working for Molecular Systems Biology. All opinions expressed in this blog are my own)

Speaking of re-using content. Alf has set up a mirror site for PLoS One. He called it PLoS Too :) and he is using it to try out some ideas on layout, microformats and features like rating. This is one funny thing about the creative commons license. As long as you give credit to the source you are free to re-use the content. Nothing stops a group of people from setting up a new journal, based on those that are published in creative commons, with a different editorial line. For this particular license you can even try to make some money from re-using the content :).

Scientific Journals blog

Blogs have been around for some time. From the wikepedia:

The term "weblog" was coined by Jorn Barger on 17 December 1997. The short form, "blog," was coined by Peter Merholz, who jokingly broke the word weblog into the phrase we blog in the sidebar of his blog Peterme.com in April or May of 1999.

Blogs in science, on the other hand, have only recently become popular. The first two traditional science news journals to pick up the raising interest in scientific blogging were The-Scientist in August 2005, and then Nature in December 2005. Since then many more scientist have picked up blogging for a variety of purposes (see review by Coturnix). The science journals have been slowly reacting. Here is a current list of blogs from science journal blogs or publishing groups. If anyone knows more please leave a comment and I will add them to the list.

Journal	Blog
The Scientist	The Scientist Blog
Scientific American	SCIAM Observations
Nature publishing group
Nature Journals	List
Nature Genetics	Action Potential
Nature Neuroscience	Free Association
Nature Methods	Methagora
Nature Medicine	Spoonful of Medicine
Nature News	Nature Newsblog
Chemistry at Nature (portal not journal)	The Sceptical Chymist
Nature publishing group	Nascent
Nature publishing group	Nautilus
Nature publishing group	Peer-to-peer
Heredity	Inherently Responsive
Public Library of Science
PLoS Blogs	List
PLoS publishing	Publishing blog
PLoS Technology	Technology blog
PLoS Medicine	PLoS Medicine blog
The Lancet	The Lancet blog
Science	The Weblog of Science Magazine"s (stopped)

Science Blogging Anthology 2006

I mentioned before that Coturnix was getting ready a list of blog posts that would go into a science blogging anthology of 2006. Twelve judges have selected 50 blog posts that will be put together in a book. The book will then be published by lulu. The judges were nice enough to select one of my posts to go in the book :)

Opening up the scientific process

Science Blogging Anthology

Coturnix from a Blog Around the Clock is organizing a science blogging anthology. I missed it during the Christmas holidays but the results are due in a couple of days. Here is the list of posts that got nominated and are now being evaluated. One of my posts made the nomination list :) cool.

Last month Roland Krause said that this type of vanity posts (like blog carnivals) are similar to spam blogs. I actually think that there is value in carnivals and other equivalent content promotion activities. They create a cheap reward system that motivates people to produce more and better content. They also provide with a layer of quality rating even if, in the case of carnivals, the posts that are submitted are self contributed. Bloggers tend to submit their best content to the carnivals.

On a related note but with a very different opinion, here is a rant on Web 2.0 And Narcissism (via Rough Type):

"What he's getting at is that this whole Web 2.0, social networking, virtual community business is essentially a pornography of the self—a projected, fictionalized self that is then worshipped by the slightly less-perfect self."

Net Neutrality Open Source Documentary

Here is an interesting project. An open documentary about net neutrality. Anyone can contribute by re-editing or tagging new videos with “net neutrality”.

Specificity and Evolvability in Protein Interaction Networks

I finally have the opportunity to blog about some of what I have worked on during last year. It has been published in PLoS Computational Biology and is freely available here in the early online release format (still in the original ugly format :). One way to use our blogs may be to add some depth to the papers that we published. Something like the extras we get when we buy the DVD of a movie ;)

Main conclusions
- Protein interactions can change at a fast rate of 1E-5 interactions per protein pair per million years
- Binding specificity is a strong determining of binding specificity with more promiscuous binding proteins having a higher rate of change of interactions.
- Human proteins involved in immune response, transport and establishment of localization, show signs of positive selection for change of interactions.

The making of
We had been using comparative genomics to search for conserved putative protein binding sites. These very conserved putative target sites were very likely to be experimentally known target sites but many other known binding sites seamed not to be so conserved. This was what got us started thinking about the evolution of these protein interactions and what might determine the rate at which interactions are gained and lost during evolution. The analysis was mostly inspired on the nice work of Andreas Wagner that first proposed a rate for the addition of new interactions in S. cerevisiae. We have tried to build on this by analyzing different species and determining also what protein properties might determine the rate at which interactions are gained and lost in evolution.

More than nodes and edges
One of the main conclusions from this work was that binding specificity also determines the rate of change of interactions during evolution. More promiscuous binding proteins not only have many binding partners but they also tend to change partners faster during evolution. To establish a proxy for binding specificity we have used structural information from the iPFAM database. In essence we have considered that protein domains that have been seen in contact with many different other domains would be more promiscuous. In general we observed that proteins containing these promiscuous domains had a high rate of change of interactions (see figure below).

This highlights something that I had stressed before, that it is important to consider protein interaction networks as more than nodes and edges. Another recent paper has also shown that it is possible and useful to use the accumulating structural information available in the PDB to obtain a more accurate representation of protein interaction networks. Philip M. Kim and co workers from the Gerstein lab (blog, webpage) published a study in Science were they have used also the iPFAM database to curate all the S. cerevisie interactions and to discriminate between interactions that use the same or different binding interfaces. With this information the authors distinguish between hubs that tend to interact with their partners mostly trough one interface or trough many interfaces. They have shown that the multi interface hubs are more restricted in evolution and more likely to be essential than single interface hubs. They have a website with presentations and additional data for this paper.

In the pipeline
To be submitted soon (hopefully), are some collaborations on how to use structural information to predict protein-protein binding specificity. With these collaborations I finish my thesis (still waiting for the defense). During the next couple of months I am off to search for a lab to work as a postdoc.

Tags: networks,protein interactions,structures

Publish your GreaseMonkey scripts

I knew it was possible to use GreaseMonkey scripts to change webpages to better suit our needs. I tried it once to get blog comments about scientific papers to show up in journal websites. Pierre and Stew have been creating several interesting scripts for postgenomic and connotea. What I did not know was that one could actually publish these scripts. I am all for publishing of smaller and finner grained scientific content but I have to say that this paper seemed like little more than a big blog post. Should we try to publish this type of work ?

Anyway :) ho ho ho , merry xmas everyone

PLoS One is up and running

I will add this blog's "voice" to the many that have already announced the start of PLoS One. This journal is a very much needed experiment in science communication online. It is being built from scratch to take advantage of the internet as the medium unlike many other journals. As Deepak mentioned in his blog, the success of One will depend mostly on us, the users, in our interest to participate with our own insight. The PLoS One team will have to worry about creating interesting reward systems around the journal to help boost participation.

I have only played around on the site for a short while but there are a couple of features that I hope that will implement in the short term.
- One that I was hoping to find at start was some form of gateways or portals for areas. The only subject navigation available seams to be the links on the right side.
- I also did not find any kind of rating system. To boost participation I think people have to start trying out simple participation systems and rating is the easiest one.
- I guess it would also be nice to have some kind of track back system or some other way to let comments come in from blog post. This would be nice for bloggers but i have to admit that few people would care :) .

There were two papers (from the same group) that caught my attention but I did not have time to read them:
Control of Canalization and Evolvability by Hsp90
Modularity and Intrinsic Evolvability of Hsp90-Buffered Change

Tags: plos,plosone,open science

Second (hellish) Life

I had a walk around Second Nature inside Second Life. I had tried SL before some months ago and this time the experience was much worse. My avatar keeps freezing when I touch objects or when I stand around idle for some time. Some other times the avatar just freezes in flight and continues in the same direction until I quit. It was just unusable.

Here is a picture from an 3D cell in the Second Nature island.


A feeble attempt to build something for the EMBL online symposium

Tags: second life,science

Modularity and Evolvability

The First Online EMBL PhD Symposium as started today with several media files available for viewing and commenting. There is an IRC channel open for discussion.

Participants can comment or add their own content to the site. I have put up a small presentation relating modularity and evolvability in proteins, language, software and the scientific process. I am no expert in any of these fields so view these analogies with a very critical eye :).

Full screen view can be access from the slideshare site

Tags: evolution,modularity,evolvability,science,open science,conference

The 6th edition of Bio::Blogs is up in Nodalpoint. Many thanks to Greg for setting it up. This edition marks half a year of Bio::Blogs and it is dedicated to conference blogging, probably one of the best examples of the usefulness of science blogging.

The 7th edition will probably be scheduled to February to skip the holiday season and Paras Chopra has volunteered to host it.

Tags: bio::blogs,blog canivals,bioblogs

EMBL online PhD symposium






(via Notes from the biomass)
EMBL is organizing the 1st PhD online symposium (4-8 December). It will be fully online, available for free to anyone. Participants can register to participate in the discussions and watch the presentations when they are made available. The users can create pages to share posters, talks or anything that might be relevant to the conference. In all, it could be a good playground to try out new ideas for online conferences. We could ask Nature to broadcast it in Nature island inside second life ? :)

Register, create your pages, share some thoughts. The topics are:
Career Development
Omics Session / Systems Biology
Scientific Communication 2.0

Konrad is one of the organizers.

Tags: open science, EMBL,conference

Connotea tag:evolution citation report

What is a scientific journal ? One possible definition could be - a content provider that filters and selects scientific content appropriate (of interest) to a particular group of people. Currently, journals select papers based on the decisions of a small group of people, maybe one or two editors supported by a few referees. The internet allows for alternative methods to select and filter content based potentially on the knowledge of a larger group of people. Eventually, these methods might one day replace the expansive editorial procedures now in place in most journals, but before that happens these approaches have to be evaluated. Also, even if we don't use these methods to replace current editorial procedures, they can be used to help us highlight the most interesting works published in certain fields.

So, why not consider tags in social bookmarking services like Connotea as scientific journals ? Here is the journal Connotea tag:evolution. I took from Connotea yesterday (21/11/2006) all papers tagged with the tag "evolution" , that were published in 2003 or 2004 (85 papers). I used the web of science to get the number of citations of each of these papers (see figure below). This was unfortunately done one by one. I am thinking of scripting some tool to do it automatically but if someone knows a better way please let me know.

As expected the most represented journals are some of the journals with higher visibility but still more than 50% of the manuscripts were tagged from more specialized journals.

So how does the average number of citations per paper of this "new journal" compare with well established journals ?

Although Connotea Evolution is low volume compared to other journals it does have a higher average citation per paper than journals such as Nature and Science. I did not separate potential non citable items from any of the groups so it should be a reasonable fair comparison.

I think this suggests that we should evaluate potential mechanism to guide us to interesting scientific content. By itself, these evaluations might establish a form of reward for the community to come up with more sophisticated tools. It is important therefore to carefully pick the measurements. I used the citations per paper but others might be more adequate.

Any group of people can use the internet to re-group scientific content (specially if it is open access) into "journals" of potentially more value than those currently available.

Tags: evolution,connotea,social bookmarking,open science,science2.0

Journals Proliferate

I only noticed today BMC also had a Systems Biology journal. There are no papers yet but the editorial board looks interesting enough. From the types of articles they expect I think they will take a lot of bioinformatics related manuscripts. This adds to two other Systems Biology journals that I am aware of: Molecular Systems Biology (also open access) and IET Systems Biology.

(via BioHacking) On a more creative note, here is the Journal of Visualized Experiments. It is a "journal" of recorded experiments that should help others learn protocols with the aid of videos. Currently the submissions are subjected only to editorial evaluation and are expected to get published in about 14 days. They plan to apply for listing in PubMed and other databases.
The videos are accompanied by a very short written explanation and are tagged for searching. There are no comments or RSS features that I could see.

Nature Methods and Nature Protocols should give this a try. By the way, Nature Protocols also publishes protocols in bioinformatics, and Nature Methods started a blog (Methagora)

With this continuing expansion of journals in all publishing houses aren't we quickly reaching a point when manuscripts will be the scarce resource ? I really hope someone develops nicer tools to suggest communications to read based on my interests. Is there a place for researchers whose job is just to associate and shuttle communications around ? Tagging communications as FOR_SMITH_J to show up in some reader with a comment: "solves your problem X".

Tags: science,science publishing,systems biology,bioinformatics

Chris Surridge explains PLoS ONE

Chris Surridge explains PLoS ONE

As part of the OpenWetWare's Seminar Series on Open Science, here is Chris Surridge explaining PLoS ONE. Some random things I remember:
- No-one reads full table of contents anymore so why not create a journal with broad scope ? (I do read full table of contents of many journals, it's the first thing I do in the morning)
- They are aiming at a very high volume (hundreds of manuscripts)
- The journal will probably have portals for subject areas
- Anyone is free to reuse the open access content, so anyone could in theory be an editor by reusing open access content and focusing it for a particular target audience.
- They might also pool in papers from other open access journals
- There will be probably a karma system to rate the contributions
- The system of having different versions of the same manuscript will not be on the first version of the journal.
- The journal might be up on the 29th of this month (not sure yet)
- Chris Surridge moves around too much :)

Tags: plos,plosone,open science

iTOL - Interactive Tree Of Life

The Bork group published recently a revised tree of life in Science. You can have a better look at the tree using this nice interactive tree viewer that they put up on the web (publication).


You can zoom in and out, re-root, swap branches, and export the trees. You can also upload your own trees and annotations to have them drawn by the viewer. Hovering over the species brings up a box with some information. Did you ever wonder who donated DNA for the human sequencing project ? The Bork group has found out for us:

Tags: bioinformatics,tools,phylogenetic tree

PLoS redesigns, PLoS ONE soon

Go have a look at the PLoS websites, they have been redesigned. I like the look but the only notable changes are a box "From the Blogosphere" that currently links to the Open Access News blog (I wonder why:) and a link to "Readers Respond" on the left, that should put more emphasis on user participation. The PLoS Medicine site has some notable differences. First they include the PLoS Medicine blog on the home page and the "From the Blogosphere" links to a Guardian article. I guess that these are customizable and left to the editors to use to point out interesting things related to the journal or field. Now ... when will PLoS Comp Bio start a blog ?
Still no journal is taking in blog comments. It would be easy to use Postgenomic's index or trackbacks to let readers comments papers trough their blogs.

There is also an editorial in PLoS Biology about PLoS ONE: "ONE for All: The Next Step for PLoS"
The only new thing I got from the editorial was the concept of portals withing PLoS ONE. I would say it sounds a bit like the Nature Gateways, an area for the aggregation of papers and other resources related to a particular field or project. Sounds like a good idea. Again, they mention that at the start it will look like any other journal and that they will build on it in time, so I don't expect much in the launch day.

Tags: plos,plos one,open access

Bio::Blogs#6 @ Nodalpoint

Greg has volunteered to host the 6th edition of Bio:Blogs at Nodalpoint (half a year already). It should take place on the 1st of December. Anyone that wants to participate just has to point out an interesting bioinformatics related blog post by email to the usual bioblogs _at_ gmail _dot_ com.

Some links:
(via postgenomic and Clinical Cases and Images) The Lancet started a blog (creatively called The Lancet blog) . If it funny that some of the oldest journals are testing new ideas in publishing leaving some of the more recent ones lagging behind.

Here is another bioinformatics related blog. From a research associate at Newcastle University, interested in neuroscience.

Tags: science,bioblogs,thelancet,scienceblogs

MeeboMe to

Fallowing the tip from Deepak I decided to give MeeboMe a try here in the blog.
Fell free to interrupt my thesis writing :) by writing something there on the box.

Tags: meebome,meebo,blog things

Personal fabrication - Update

Several years ago I read a book by Nicholas Negroponte entitled "Being Digital". It was a really great introduction to the digital revolution and provided with a glimpse to some of the changes that are still ongoing in our society. I find fascinating the ability that some technologies have to change so much our ways of living, opening up with a simple stroke so many new possibilities. The digital revolution was one of these events. An apparently simple concept of having information coded in a digital format that can be transported anywhere at near instantaneous speeds. Now we have the internet that as provided with so many wonderful advantages. I can learn anything I want, provided I have time. I can collaborate with people I have never even met before to build new things. It is difficult even for me to imagine living in an unwired world (but that might be a bit geeky thing to say :).

I read today this profile on Neil Gershenfeld and his work on home manufacturing at MIT and I though that this would also be a very empowering technology. He is pushing the concept of personal fabrication, enabling anyone to easily create any physical thing. He wants to bring the same speed to making atoms that we have today for bits. You could grab a funny chair design that you made in your computer, send it to your friends by email and they would open it .. very literally by "printing" it and sitting on it to try it out.
I guess there are lots of details to think about, but generally the idea sounds fun.

I was thinking that some companies should have a go at this already. I am not really into design but I guess that several companies today focus on constantly renewing their stock with new designs and trend setting ideas. Why not have an Ikea section of "do your own" furniture. Something like social web manufacturing of clothes, accessories, furniture, etc.

Also, why not have collection of the most used objects in Second Life, built every quarter or half a year. Second Life authors would have to agree and probably negotiate a cut of the profit.
Here is someone building a guitar :)

Where is the print button to get one of those right now?

Update:
I am really behind on this meme. I few more clicks and I found this blog post in MIT Advertising lab. From there I found this company that specializes in bringing virtual objects to life.

A blog post by Ian Hughes on home fabrication.
A wiki page fab@home with instructions to make "fabbers", machines that can make almost anything, right on your desktop.

Tags: Personal fabrication

Activating RNAs (RNAa) - another twist

A paper published online in PNAS described a possible new form of regulation of gene expression by small RNAs. The authors found that small dsRNAs can also serve as transcriptional activators. They showed that the mechanism for gene expression activation also prefers dsRNAs of ~21 nt in size and requires the Argonaute 2 protein.

The story was covered by a news article in Science. From the news article it looks like there is some fear that the result might be due to indirect effects (inactivation of other genes leading to gene expression activation). Also, some wonder why this as not been picked up before by other studies.

I am very tempted right now to get some of the high-throughput screens of RNAi to try dig out some more examples that might have gone unnoticed (if I actually had any time to do it :).

Tags: science,RNAa,dsRNAs

Bio::Blogs#5

The November edition of our bioinformatics blog journal is up at Chris' blog. This edition is mostly focused on potencially interesting tools to use, including Zotero, a bibliography manager Firefox extension and Bioclipse, an open-source workbench for bio/chemi-informatics.

I forgot to ask Chris to link to the bio::blogs icon challenge. I guess we can run it for another month. If you don't like these two icons and you think you can do better give it a try :) until next month.

We are in need of a volunteer to host the December edition. If you run a bioinformatics related blog and are interested send in a link to your blog to bioblogs at gmail.com or leave a comment below.

Tags: bioblogs,blog carnival,blog journal,bioinformatics

Networks in the sky: a new concept of modularity?

A recent paper by Batada and colleagues published in PLoS Biology tries to consolidate the available information on protein-protein interactions for S. cerevisiae. The authors have attempted to create a high-confidence set of interactions that they then further analyze. The main conclusion from the paper is that the highly connected proteins (usually referred to as protein hubs) do not avoid each other, as was previously put forward by other authors. From this observation they suggest that we should rethink our view of modularity in cellular networks. Cellular interaction networks should be viewed, not as altocumulus clouds, “i.e., cotton ball-like structures sparsely connected by thin wisps”, but instead as the “continuous dense aggregations of stratus clouds”.

Although I find it useful to constantly update our view of cellular networks trough the consolidation of available data, I think some words of caution remained unsaid in this work.

The new consolidated protein interaction network was obtained mainly from the addition of a recent curation effort from the literature, to the already available high throughput interaction datasets obtained using yeast-two-hybrid and affinity methods. The majority of the interactions added are from affinity methods. This leads me to one of points I think are not usually mentioned in this type of efforts, that not all methods will provide the same information. For example, I think that affinity methods mostly inform us that two proteins share the same complex. When a protein is tagged and used as a bait to capture prey proteins, the identified preys should belong to the same complex but it is not obvious that there should be a direct interaction between the two. However this was the assumption used here in this work. This is usually referred to as the spoke model (see figure 1).

I have tried to evaluate how likely are bait-prey interactions to occur, when compared to prey-prey interactions, using either structural information or yeast-two-hybrid interaction data (see table 1 and table 2).

Table 1 – Pull down experiments were taken from Gavin et al, 2002. For each individually reported pull down, potential bait-prey and prey-prey interactions were counted if the corresponding proteins had known PFAM domains. Using the database of domain structural interactions (iPFAM), I tried to search for plausible domain-domain interactions that could account for the protein interaction. Bait-prey interactions are roughly 2 times more likely to be explainable by a known domain-domain interactions currently stored in structural databases, than prey-prey interactions.
Table 2 – Pull down experiments were taken from Gavin et al, 2002. For each individually reported pull down, potential bait-prey and prey-prey interactions were counted. The overlap of these interactions with known yeast-two-hybrid interactions is shown. Bait-prey interactions are roughly 2 times more likely to be observed in a yeast-two-hybrid study than prey-prey interactions.

What one could conclude from this is that in fact bait-prey interactions are more likely to occur than prey-prey interactions but also that a small percentage of the bait-prey interactions can be validated with a method that is more likely to measure direct interactions. Using both domain-domain structural information and yeast-two-hybrid studies, 20% of the bait-prey interactions can be accounted for. Although this value depends on our current knowledge of domain-domain interactions and the coverage of yeast-two-hybrid studied it should at least be discussed. One problem in using this model can be for example seen in figure two. When multiple baits are used for the same complex, it is easy to create artificially interacting hubs, when extrapolating binary interactions from affinity data.

In all fairness, in this study, the authors only took as a true interaction, one that was observed more than once but they also consider multiple affinity observations as confirming a direct interaction. It would be useful to come up with better methods to extrapolate from complexes to binary interactions. I hope the differences observed in this work regarding hub-hub interactions are not mainly due to the proportion of interactions extrapolated from affinity methods.

One observation that the authors used to support their claims was that, apparently, the fraction of hub-hub interactions depends on the scale of the experiment (see figure 3A taken from the authors paper). According to this result, experiments reporting higher number of interactions tend to have a lower fraction of hub-hub interactions. Hubs were defined, in the figure legend, as the 10% more connected proteins in the network, but in the results description are defined as the 5% more connected proteins. One thing that the authors failed to show is how this fraction of hub-hub interactions depends just on the size of the network. I have used the network given in the manuscript and randomly sampled 10% to 90% of the interactions (repeated 50 times) to plot the dependence of the fraction of hub-hub interactions on network size (see figure 3B). Hubs were defined as the 5% more connected proteins.

What we can see is that the fraction of hub-hub interactions depends on the size of the network, decreasing for smaller network sizes. Can this explain the result observed by the authors? In figure 3A, taken from the authors’ paper, the whole network was binned by the number of interactions reported per paper. I have tried to calculate the size of different networks obtained from binning according to the scale of the experiment (see table 3).

I would say that, although I could not reproduce exactly the same bins reported in the paper, the trend is for a decrease of network size when comparing all interactions reported in small-scale studies to those reported in medium-scale experiments. Therefore I think the observed result is mostly explained by differences in network size. In fact, if one would take all interactions reported in experiments observing at least 30 interactions the fraction of hub-hub interactions observed would be even higher than in the network obtained from very small scale experiments.

Summary
I think this manuscript highlights that we should constantly re-evaluate our views on cellular networks as more data is made available. Although the concerns raised here do not contradict their conclusions I think they should have been more carefully discussed. In particular I think we require better methods to extrapolate binary interactions from affinity methods and that it is important to mention that this might lead to false positive interactions. Also, there is a strong effect of network size on the observed fraction of hub-hub interactions. This might explain both the observed increase of hub-hub interactions with increase in the coverage and the observed dependence of the fraction of hub-hub interactions on the scale of the experiment.

Tags: original_research,networks,review

I googled from Yahoo too

There are some google people going nuts over at the official Google blog. They don't want us common mortals to use the word Google as a verb when searching trough something other than their website. That is a very good away to attract some negative feelings.

While we're pleased that so many people think of us when they think of searching the web, let's face it, we do have a brand to protect, so we'd like to make clear that you should please only use "Google" when you’re actually referring to Google Inc. and our services.

So, let me say how much I like to google from Firefox for example. I actually google in Firefox most everything. When I don't google from firefox I google from my taksbar. Right now both are set to actually google in Google, but many more nice blog posts like this one and I migh actually give Live search another try.

Tags: Google,karma,Live

Focus on Systems Biology: a User's Guide

Nature Cell Biology and Nature Reviews Molecular Cell Biology are jointly producing a Focus on Systems Biology: a User's Guide. It contains several reviews on the topics related to data management, bioinformatics and modelling (probably sub only)

Tags: systems biology,bioinformatics,modelling

PLoS ONE - Spread the Word

PLoS ONE will soon make its debut. They seem to be going strong with 210 submissions since the initial launch on the 4th of August. Last week alone they got 30 papers to review.

According to an email they sent to the mailing list they have now 179 members in the editorial board but they encourage scientists from areas that are not yet well covered in the PLoS ONE editorial board to work with the journal.

They have also added some goodies to download for anyone interested in spreading the word. Grab a flyer, print it and post it up on your work place :)

Tags: plos one,open access,plos

Bio::Blogs icon entry

Here is an icon made by Rick from My Biotech Life:

I really like how he managed to fit the "bioinformatics blog journal" on top of bio::blogs. He is right that it is a bit big for an icon but it looks really great :). Thanks for the effort.
I guess we can keep the challenge open until the end of the month and then choose one during the edition. If anyone wants to submit an entry by email send it to bioblogs _at_ gmail.com.

Recently added feeds - more science bloggers

The blog of Jonathan Eisen, an evolutionary biologist and a Professor at U. C. Davis (Eisen lab at OpenWetWare).

The blog of Marc Gerstein, Prof. Biomedical Informatics at Yale (lab site)

(via mndoci) The Omics World, a blog about : "Genomics, life science technology , computational biology , structural biology and their inter-relationships"

Changing scientific publishing

There was a panel discussion about the future of scientific publishing in the Neuroscience 2006 conference. Sandra Aamodt of Nature's Action Potencial blog, Jake Young from Pure Pedantry and Dave Munger from Cognitive Daily have blogged their thoughts on what was talked about.

There are two main points under discussion. One is how can the publishers make the switch to an open access model (where all the content is available) in a sustainable way. My impression from what I read and from talking to other people is that a lot of the publishers are or will be experimenting with open access options and if the demand is high enough this will be the direction they will go for.

The other big discussion is how to transition to the web, taking advantage of other possible tools that are not available in the print world. This issue is unfortunately much less explored. One of reasons is because they are stuck in the first issue. Another reason is that the people who are in charge of editorial boards are taking some time to realise the potential of the internet. Blogs and wikis for them are something messy and chaotic that teens use.

Is there any science related activities on blogs and wikis ?
- according the September statistics there are about 1500 science related blog posts per week coming from about 200 science blogs register in postgenomic
- postgenomic has gathered comments on about 2500 papers
- there are about 1000 science related blogs registered in Technorati.
- there are more than 1500 scientists helping out to build the OpenWetWare wiki.

I did not try to get numbers from connotea and citeulike but I am sure that are a lot of papers being tagged and rated every day.
Given that the science community as just started to participate online in blogs and wikis I guess the numbers will only increase.

One interesting detail, postgenomic keeps track of the most referenced journals (on indexed blogs) and the top tree are Nature, Science and ArXiv. The third most blogged about "journal" is a repository of manuscripts that have not yet been peer reviewed.

There are all sorts of possible criticism that one can make of these numbers. Technorati numbers are probably inflated with spam blogs and blogs that are not really science related, comments indexed by postgenomic can be anything from one line to a full review, etc. I just wanted to show that there is already a lot of science communication going on in blogs and wikis.

Bio::Blogs icon challenge

Bio::Blogs, the bioinformatics blog carnival/journal is going for it's 5th edition. It will be up on the 1st of November on Chris' blog. Maybe we could celebrate by trying to create an icon to represent Bio::Blogs. I quickly stole some ideas (I think from something I saw in Neil's blog :) to make this up:



It should not be difficult to make something better :) Does anyone want to try ?

The 3rd EMBL Biennial Symposium

One of the nice things about being at EMBL is that we can sneak into the ongoing conferences. This one is entitled: "From functional genomics to systems biology" and today was the first day.

I will just highlight some of the talks that I found most interesting. One was by a group leader here at EMBL, Lars Steinmetz who has been using tilling arrays (microarrays that try to cover the whole genome) in S. cerevisiae to look at the expression of non-coding regions in the genome. Although S. cerevisiae does not have the components for RNA interference, it does seem to have many non coding RNAs that are expressed. Many seem to be antisense to coding genes and also they could identify some of these non coding RNAs that were oscillating in a cell-cycle dependent manner. They are also using this arrays to look at the differences of expression of different strains and to study events of recombination.

The talk that I most enjoyed today was by Alexander van Oudenaarden. His group is studying small cellular circuits and cellular noise. He showed at lot of data on the galactose inducible promoter, detailed in this picture I took from their site :

He showed that the activity of the Gal4 promoter can be in two separable steady states and that this is history dependent. So yeast cells have memory in their metabolic state. He also showed that this state is inherited by the daughter cells and that they can manipulate the systems such that circuit can have a more or less stable memory. Also, not only the state is inherited but even the likelihood that the cells will switch state is also transmitted to the daughter cells. They studied this with flow cytometry to quantify single cell measurements and with microscopy to be able to follow the lineages. All of this was well integrated into predictive models of the system. Extra points for having a webpage on OpenWetWare :)

When will we be at a point were we can actually take high-throughput assays, combine them, make a model of modules that we find and have this detailed understanding of how they work ?

Google Data Privacy - GDP


(via Konrad) I like this idea of having some way to tell Google what data to keep and for how long to keep it. Some one-point access to how much they really know about me :). I don't mind to much that they have this information, but I would like to be able to control it. They even have gotten really good at serving me ads. If it is an ad pointing to something I want to go check out than it's a good ad.
I would go a step further then. I want to own that information. I want to be able to take it somewhere else and share it with other services that might work better if they know these things about me. Amazon would probably suggest more interesting things.

So, I also want a Google Data Privacy.

For more check out AttentionTrust.

Community consultation @ Nature Biotech

Open peer review at Nat Biotech ? At least this was the first time I noticed it:

Various scientific communities are engaged in producing data-reporting standards similar to the MIAME guidelines for microarray data. Some of these papers are under consideration for publication in Nature Biotechnology. To encourage broad participation in the standards-development process, we are making the papers freely available at http://www.nature.com/nbt/consult/index.html and we urge you to participate and send us your comments and suggestions, which will be carefully considered by the authors, reviewers and editors.

Currently they are asking for comments on the proposal for: The Minimum Information required for reporting a Molecular Interaction Experiment (MIMIx)(PDF).