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