Sunday, October 08, 2006

Those funny buzzwords in research

I find it interesting to keep track of buzzwords in science. What exactly is a buzzword ? Here are some definitions from wikipedia:
A buzzword (also known as a fashion word or vogue word) is an idiom, often a neologism, commonly used in managerial, technical, administrative, and sometimes political environments.
Buzzwords appear ubiquitously but their actual meanings often remain unclear.
Buzzwords are typically intended to create the impression of knowledge for a wide audience.


Some of the buzzwords in science are used carve out sub fields of research, like systems biology, synthetic biology, comparative genomics, bioinformatics, metagenomics. What makes them more or less trendy ? The attention they are able to draw is (i guess) based on who is promoting them, the coverage they get in journals and probably more importantly the funding bodies perception of their relative importance. Ofcourse a well backed meme will be perceived as important, will receive more funding and the trend cycle kicks in. Then, the creation of a new buzzwords in science and ultimatly of new fields is very much dependent on marketing. Nothing new there, right?

On the other hand it is useful to be able to create some boxes around a couple of ideas and to build communities that can together work on a problem. These buzzwords help people to identify with each other as a part of the same community. Being forced to define the problems that the X-omics or X-biology faces helps us to tackle them, propouse new methods and to apply for grants. So, I think buzzwords are necessary to identify a group of related problems and to build communities around them.

What got this whole rant started ? :) A review by Eugene V Koonin entitled: "Evolutionary systems biology: links between gene evolution and function". I recently posted about my interest in the effect of mutation in biological systems so I am interested in this meme. Do we really need to call it "evolutionary systems biology" ? :)

Anyway, some facts about it.
I think it was first proposed as a field in a paper in April 2005: "Genomes, phylogeny, and evolutionary systems biology". At this time there are 704 hits in Google (one more after they crawl this post) and 6 papers in pubmed. Three of these are just because the CNIO has an "Evolutionary systems biology Initiative" in the Structural and Computational Biology Program.

There are at least 8 groups or people supporting the meme in their research interests or even in the name of the group.

There is one poster with this buzzword in the title in ICSB-2006, that is starting tomorrow.

What is it about ?

"To understand molecular evolution and gene regulation on the scale of complete genomes and biological systems."

"Evolutionary constraints on the trajectories are reflected at the molecular level, and can be probed by a number of techniques including biochemistry and comparative analysis of extant successful protein sequences. These constraints should also be reflected at higher levels of organization in biological systems, such as biochemical pathways. Integrating information across these levels of organization is critical for understanding the evolution of biological systems."


I'll probably check back on this in some time.

Friday, October 06, 2006

The igNobel prizes

The prizes for improbable research are back again. I think they are currently suffering from too much load on their servers so here is the link to Google News.

It is always good the have a bit of a laugh at how focused some of the scientific research can be. So, here are some of my favourites :)

BIOLOGY — Bart Knols and Ruurd de Jong, for showing that female malaria mosquitoes are attracted equally to the smell of Limburger cheese and to the smell of human feet.

MEDICINE — Francis Fesmire, for his medical case report “Termination of Intractable Hiccups with Digital Rectal Massage”; and Majed Odeh, Harry Bassan, and Arie Oliven for their subsequent medical case report.

PHYSICS — Basile Audoly and Sebastien Neukirch, for their insights into why dry spaghetti often breaks into more than two pieces when bent.

From the abstract:
"When thin brittle rods such as dry spaghetti pasta are bent beyond their limit curvature, they often break into more than two pieces, typically three or four. With the aim to understand these multiple breakings, we study the dynamics of a rod bent just below its limit curvature and suddenly released at one end. We find that the sudden relaxation of the curvature at the newly freed end leads to a burst of flexural waves, whose dynamics are described by a self-similar solution with no adjustable parameters. These flexural waves locally increase the curvature in the rod and we argue that this counter-intuitive mechanism is responsible for the fragmentation of brittle rods under bending. A simple experiment supporting the claim is presented."


ACOUSTICS — D. Lynn Halpern, Randolph Blake and James Hillenbrand for their experiments to learn why people dislike the sound of fingernails on a chalkboard.

(via the spotlight radio):
"The scientists performed experiments on willing people. They chose one of the most disliked sounds. Do you recognise it? Can you remember sitting in a classroom at school? The teacher would stand at the front. She would write on a blackboard. There was always someone who waited for the teacher to leave the room. They would run to the front of the room. And then, they put their fingers at the top of the black board. They moved their fingernails slowly down the board. Listening to this sound still makes you feel horrible!"

Wednesday, October 04, 2006

SlideShare - Share your presentations

SlideShare is online tool to upload and share presentations. Very much like what Youtube does with video. The presentations are uploaded with some metadata (tags, tittle and description) and the content is searchable. Once the presentation is uploaded you get a direct link to it and the possibility to embed it in webpages (like the blog). From the webpage you can also start a full-screen view that allows you to present the slides from any pc with net and a browser. The only complain so far is that it did not convert the animations I had in the slides but they should be working on it.

I gave it a quick go with some slides of mine. Jokes on my poor design skills are not very welcomed :).




Google widgets set free

Google announced that their widgets (or gadgets) can now be used on third party webpages. I thought of trying some parasitic computing. Creating some modules that would store state. Whenever I would see a gadget on a page it would query another gadgets on some other page, retrieve or set some state, do something with it and set some state on a third widget somewhere else.
Unfortunately for some reason they explicitly say that recording state will invalidate your gadget:
* It cannot be inlined. For example, a syndicated gadget cannot modify the container page.
* It cannot store state. For example, a syndicated gadget cannot be a to-do list that stores personal list items for each user.
* Its functionality should not be dependent on each user specifying different user preferences.


I am not sure they work with blogs, but here goes a try.



Tuesday, October 03, 2006

(via Neil) Pansapiens and Chris, regular visitors at Nodalpoint, started two new bioinformatic related blogs. As I mentioned before Chris will host the next edition of BioBlogs.


Sunday, October 01, 2006

Bio::Blogs#4

Another month as gone by and so we have again another round up of some bioinformatic related posts on Bio::Blogs. The 4th edition is up in Sandra Porter's blog, Discovering Biology in a Digital World. The best way to keep up with the carnival is to get the rss feed from the Bio::Blogs blog.
Anyone interested in participating can submit links to interesting posts to bioblogs at gmail com. Bio::Blogs is hosted every month by a different blog and the November 1st edition will be hosted by Chris. Any bioinformatics related blog can host the blog by sending an email to the Bio::Blogs mail.

Saturday, September 30, 2006

Evolution of transcription networks

As early as in 1975, Mary-Claire King and Allan Wilson observed that there was very little change in many human proteins when compared to their chimp counterparts. From this they postulated the divergence between humans and chimpanzees should be attributed to changes in regulatory regions, that would impact on the expression levels of the proteins.

So, this brings us to one possible consequence of mutations on biological systems. Genomic variation can alter the regulatory networks of the cell, either by mutating transcription factors or by changing the regulatory binding sites where the transcription factors bind to in the genome.

To what extend can the expression change with evolution? One way to gauge for the possible rate of change is to look at recently duplicated proteins pairs within the same species and check how related in expression are they. Several studies (for review see here) have shown that expression divergence occurs quickly after gene duplication. Papp and colleagues provided with a possible mechanism for this change. When they studied the up-stream region of duplicated proteins they saw that the number of shared binding sites decreases with the age of the duplication although the total number of binding sites stays fairly constant.

This provides with a model of change of expression after duplication by quick lost and gain of binding sites by mutations in the regulatory regions.

To determine the impact of divergence on the changes in the regulatory networks one can also look at how conserved are the regulatory regions of the same proteins in different species (orthologs).
Dermitzakis and Clark
have calculated that between 32% to 40% of the human transcription factor binding sites are functional in rodents, providing evidence for significant change in regulatory sites.

Gash and colleagues used a different approach to study the cis-regulatory region of S. cerevisiae proteins. They looked at the conservation of binding consensus in several other fungi spanning a very broad evolutionary distance (see figure 1, adapted from the same paper). They have looked at groups of proteins regulated by the same transcription factor and calculated over-represented sequence motifs in their regulatory region. These over-represented motifs likely represent the binding specificity of the transcription factor . They next checked if the same over-represented motif is observed or not in the regulatory regions of orthologous proteins. The result (figure 1) is that the binding consensus is mostly conserved even in species that have diverged from S. cerevisiae a long time ago (~400My). This seems a bit contradictory with the previous results but actually they do not say that the actual biding sites are conserved. My interpretation from their results is that a sufficient number of binding sites are conserved so that we still see an over-representation of the motif. What we can also see is that the binding specificity of the transcription factor is mostly conserved.


So more generally, what emerges is that expression change occurs mostly through changes in regulatory regions and not so much trough changes in the binding specificity of the transcription factors. To put in in another way, the binding sites are more likely to change then the binding properties of the transcription factors.

These results tell us that genomic variation can indeed change the regulatory networks but how does this impact on phenotypes. Two recent studies looked at particular examples of regulatory changes in S. cerevisiae.


A study from the Barkai lab has linked a change from aerobic to anaerobic growth to the loss of a specific regulatory site in several genes, providing evidence that regularly changes can impact on phenotypes.
To counter this, another study, this time on the mating of yeast has shown that the same phenotype can be observed even if the regulatory mechanism have changed.

These individual examples are just a taste of what we might expect in the future. They do show that regulatory plasticity can be used by the cell to generate phenotypic change but also that selection for phenotype can maintain a function even if the underlying molecular details are not the same.


Friday, September 29, 2006

Submit your posts to Bio::Blogs #4

The 4th edition of Bio::Blogs is being hosted by Sandra Porter. We are still on time to send in out links either to her directly (see here) or to the bioblogs email (bioblogs at gmail.com).
The September edition will be hosted by Chris in his Fourth Floor Studio. If you want to host future edition feel free to volunteer.

Thursday, September 28, 2006

Why do I like evolution in biological systems

One of my fascinations with biology are the amazingly different levels of abstraction one can choose to study biological systems. From molecular details and dynamics of proteins and RNA, with their different conformations and chemical activities to how these components interact with each other to produce the required functions inside the cell. The interactions of cells during development or bacterial communities. How firing neurons compute stimuli and produce behaviour and the interplay of species in ecosystems.

I guess what all of these things have in common is that, at any given level of abstraction, it is possible to describe components (i.e, atoms, proteins, cells) that can apparently be described with a reasonable limited set of properties. In all cases the interaction of the described components result in emergent complex patterns that are not easily predictable. All of this just means that we really don't know much about these systems :).


To complicate the story a little more these are evolving systems with constant genomic variability produced by mutation, recombination, segment and/or genome duplication events. How is this variability propagated through these layers of complexity ? What can be the consequences of a mutation ? Changing an amino acid in a protein might disrupt the binding to another cellular component. In turn this could alter a pathway, changing an oscillatory response to a transient one upon a certain environmental clue. This could be enough to modify the development and morphology of a species and how it relates to others in the ecosystem.

Given the slow nature of evolutionary change we can assume that in many cases we are studying a snapshot of it's dynamic nature. Like studying in much detail a frame of an ongoing movie. So, what is the point ? Understanding how something was "produced" helps us understand what to expect from it's functions. Also, understanding the impact of genome variability helps us determine to what extent biological features are conserved between species.

I'll try to devote some future posts on what is known about the impact of mutations and other genome changes in different levels of biological complexity.

Monday, September 25, 2006

The evolution of genome complexity

There is a nice review out in BioEssays on the non-adaptive evolution of genome complexity. It focuses on the work of Michael Lynch and in particular a recent paper proposing a general theory about the evolution of genome complexity grounded on population genetics.
Lynch argues that the eukaryotic genome structure originated due to the reduced selection pressures associated with the small effective population sizes of eukaryotic species. That is, most of the complex features of eukaryotic genomes are the result of stochastic search through neutral or slightly deleterious mutations that are not purged trough selection (due to the reduced selection pressures in small populations).

I still have a hard time getting my head around this theory. I should try to strengthen my population genetics background. Lynch does not say that adaptation does not play a role. If I get it right he is just arguing that there is a relaxed search in reduced populations. This would be conceptually the same as relaxing a fitness search algorithm such that it would not get stuck in local optima (see fitness landscape).
One possibility to study this theory further could be maybe to take a realistic model of a simple cell and to do evolution studies in silico. Something like this was proposed recently in a Biology Direct paper by Neyfakh and colleagues.

I know some bloggers out there that would have a more informed opinion on this. It would be nice if there was some way to informally request an opinion just by linking in a particular way for example :).

Friday, September 15, 2006

Comparative Interactomics on the rise (II)

Two papers on interaction network alignment caught my attention recently. Both of them are supposably more efficient ways of doing network comparison than the previously published PathBlast from the Ideker lab.

The first one called Græmlin was published in Genome Research and the second one developed by Mehmet Koyuturk is called Mule(PDF) and is in press in the Journal of Computational Biology.

More on the buzz department, the MIT technology reviews elected comparative interactomics one of 10 “emerging technologies” of the year. Highlighting Ideker and Palsson as two of the people pushing the idea forward.

That's it, I figure the meme gained enough traction to "spread" in the wild and we can expect several variations on the algorithms to surely continue to flow along with even more interaction networks.
Psi-Network-Blast anyone ?

Open access publishing (physicists viewpoint)

There is a very interesting discussion going on about open access publishing in a physics blog. The author also links to a recent editorial in Nature Physics.

A lot of the discussions are on how to certify content after submission to a pre-print server and how expensive should the whole process really be. Going through it the thing that most impressed me is that everyone seems to accept naturally the usefulness of a preprint server. Ken Muldrew in one of the comments says:

"something like the arXiv is sort of a bridge between conference talks and publications; a new phenomenon that doesn’t replace the old ways but rather adds to them, like email as it relates to phone conversations and page-written letters."

So why are there not more bioinformatics manuscripts in pre-print servers ? Most bioinformatic/computational biology journals accept submissions from papers already in pre-print servers. I subscribe to the arXiv feed on quantitative biology but most papers seem to a bit away from biology when compared to work published in say Bioinformatics, PLoS Comp Bio and BMC Bionformatics. This recent manuscript about horizontal gene transfer shows that arXiv does accept the type of work that I might participate in so I will try to in the future submit there first.



Thursday, September 14, 2006

Marc Vidal interview in a podcast

(via My Biotech Life) Rick pointed me to a podcast series called Futures in Biotech. I am listening to a two part interview with Marc (Interactomes) Vidal, explaining his interest in parts and networks on a very accessible level. There are some interesting historical little stories for those more familiar with the field.


Monday, September 11, 2006

Postgenomic Upgrade

I don't remember reading any announcement but I guess Stew upgraded Postgenomic. It's full of extra information that will give anyone a chance to procrastinate for some time. Did you ever wonder what is the Gunning-Fog Index of your blog ? Your incoming bloglove ? (whatever that means) Your most popular blog post ? Go have a look at PG.

He also added a section on original research that I guess is still experimental. My two posts on the correlation between protein age and protein interactions are there but I guess he had to mark them by hand.

On a related note, Stew released a greasemonkey script to add links to postgenomic from connotea. I would love to see journals starting to link directly to postgenomic without us having to use greasemonkey scripts. This would give bloggers an extra little incentive to write some comments on papers and for the journals it's free content and extra attention on their sites.

Now .. back to my thesis ...

Friday, September 08, 2006

Building reality online (the lonelygirl15 meme)


I am not a big fan of video sites so today was the first day I heard about lonelygirl15. She is a very famous video blogger with videos seen a total of about 2 million times. The interesting thing is that she does not actually exist. She is part of an art project intent on doing something like a wiki soap:

Thank you so much for enjoying our show so far. We are amazed by the overwhelmingly positive response to our videos; it has exceeded our wildest expectations. With your help we believe we are witnessing the birth of a new art form. Our intention from the outset has been to tell a story-- A story that could only be told using the medium of video blogs and the distribution power of the internet. A story that is interactive and constantly evolving with the audience.

Even if people lose interest now that they know she is not real, the fact was that they were drawn into her fabricated life. Is this ethically correct ?
I guess what I am getting at is that we are getting better at creating virtual reality. The truth is what the majority of people perceive to be true, the wiki kind of truth. This is already the case in physical reality with mass media having a strong effect on what is actually perceived. What I think is that this manipulation of masses and crowd effects are much stronger online.

Tuesday, September 05, 2006

Social network dynamics in a conference setting

(disclaimer: This was not peer reviewed and is not serious at all :)

To study the dynamics in social network topology we decided evaluate how some nodes (also called humans) interact in defined experimental conditions. We used the scientific meeting setting that we think can serve as a model for this type of studies. We observed human-human interactions during the meeting breaks by taking snapshots and calculating inter-human distances. We defined an arbitrary cut-off to determine the binary interactions between all the humans present in the study.

The first analysis we preformed was under the so call "conference breaks" model where our nodes are allowed to interact for brief time intervals after being subjected lengthy lectures.
We observed an interesting clustered network topology that can be described with a power law distribution. Most nodes in the network have few interactions while a small fractions of humans was found to consistently interact with a large number of other nodes. We found also some nodes that did not show any interactions in our studies even when several "conference breaks" were preformed. We believe that these could be pseudo-humans that were included in our study by mistake. These pseudo-humans might be on the way to extinction from the humeone.

Having built this network of human-human interaction on a large scale we decided to investigate what human properties might be correlated with human hubs. We used previous large-scale studies of human properties like height, gender and number of papers published to test this.
We show here that although gender shows a significant correlation with human hubness, the best predictor for hubs in the conference breaks networks is actually number of papers published. We tried to refine this further by introducing a new human measurement we call "hypeness". Hypeness of a human was calculated as a modification of the number of papers published weighted by the impact factor of the journals where the papers were published and also the number of times cited in popular media articles. We show here that hypeness does significant better at predicting hub nodes in this network.

Given that networks are dynamic we set out to map the changes in network structure with time. To simulate this we perturbed the gathering using a small-compound (EtOH) that we administered in liquid form. With time we observed a noticeable change in the network. Although the overall topological properties were maintained, the nature of the hubs changed dramatically. In this new network state that we call the "drunk" state, the best predictor for the highly connected hubs is clearly gender. We believe this clearly proves that social networks in conference settings are very dynamic with time.

To prove that gender was indeed the best indicator of hubness and not some strange artifact we used deletions studies. Random female nodes where struck with a sudden case of "sleepiness" and the perturbed network was observed. We show here that random female deletion leads to a rapid collapse of the network. The same is not observed with random deletion of the hypest nodes, proving our initial proposition.
Propagation of Errors in Review Articles

Thomas J. Katz signs a small letter in Science warning us about the propagation of errors in review articles. The author gives a scary example of an incorrect citation propagated through 9 reviews (if I counted correctly). The cited paper does not contain the experiment that all the reviews mention and as it seems it was actually never published anywhere. Very scary.
As more science moves online with more individual voices, will this propagation of errors be accentuated or reduced?


How to recognize you have become senior faculty

I am back from holidays and trying to plow trough the RSS feeds/content alerts that accumulated in these two weeks. I might post on couple of things that catch my eye.
Here is a funny editorial from Gregory A Petsko talking about the project to sequence Homo neanderthalensis.
The editorial is actually more about senior faculty members and in particular how to identify one:

- You are senior faculty if you can actually remember when more than 10% of submitted grants got funded.
- You are senior faculty if you can remember when there was only one Nature.
You are senior faculty if you still get a lot of invitations to meetings, but they're all to deliver after-dinner talks.
- You are senior faculty if students sometimes ask you if you ever heard Franklin in person, and they mean Benjamin, not Aretha.
- You are senior faculty if a junior colleague wants to know what it was like before computers, and you can tell her.
- You are senior faculty when the second joint on the little finger of your left hand is the only joint that isn't stiff at the end of a long seminar.
- You are senior faculty if you sleep through most of those long seminars.
- You are senior faculty if you visit the Museum of Natural History, and the dummies in the exhibit of Stone Age man all remind you of people you went to school with.
- You are senior faculty if you find yourself saying "Back in my day" or "When I was your age" at least twice a week.
- You are senior faculty if you actually know what investigator-initiated, hypothesis-driven research means.
- You are senior faculty if you occasionally think that maybe you should attend a faculty meeting once in a while.
- You are senior faculty when your CV includes papers you can't remember writing.

Monday, September 04, 2006

Bio::Blogs #3

The third edition of Bio::Blogs was released a couple of days ago in business|bytes|genes|molecules.
I particularly enjoyed the nice discussions going on in evolgen , about the rifts in scientific communities and in Neil's blog regarding structural genomics data.

The next Bio::Blogs will be edited by Sandra Porter. Send your links and offers to host future editions to bioblogs{at}gmail.com.

Sunday, August 27, 2006

Bio::Blogs #3 - call for submissions

The third edition of Bio::Blogs will be up on the 1st of September, edited by mndoci. Send your submissions to the usual email bioblogs {at} gmail.com. There were few submissions so far. It might be a slow month if a lot of people took some time off, or maybe most people are waiting for the last day as usual.

I am back from holidays, trying to digest the emails and RSS feeds accumulated in two weeks. I miss the beach already :).

Tuesday, August 15, 2006

Interactome Networks conference

I am going for a two week holidays tomorrow. I really need some boring relaxing days by the beach without thinking to much about anything :).

After that I am going to a conference, Interactome Networks on the Wellcome Trust Genome Campus in Hinxton, UK. I will give a short talk about my last project - "Specificity and evolvability in eukaryotic protein interaction networks". I will try to blog some of the talks, either here or in Nodalpoint.
Here is the current list of talks and posters. If by any chance you are not going and are particularly interested in some of the titles let me know and I will try to have a look.

Sunday, August 13, 2006

Science Foo Camp

I am to sleepy to post a coherent account of what happened today at scifoo, I'll try to do it tomorrow in Nodalpoint. It's an amazing mixture of people that they gathered here, social/bio/physics/computer scientists, science fiction writers (futurists?), journal editors, open access and open science advocates and googlers.

To ilustrate how chaotic the meeting has been, here is a picture of the session planing board they put up.

So anyone can just grab a pen and fill up a slot. The only problem so far was actually having too many parallel interesting sessions.

Thursday, August 10, 2006

Science Foo Camp

I am going to California this weekend to attend the Science Foo Camp. An event organized by Nature/O'Reilly and hosted by Google. Yeap I get to visit the Googleplex :) (I admit it am I geek). It has been fun to see the event getting set up. It started with a wiki page seeded with some ideas from O'Reilly and some instructions. Then everyone started editing their bios and suggesting/offering talks.
I will be blogging my impressions of the event over at Nodalpoint but probably a good way to keep track of the event is to take a look at the scifoo tag in connotea.

(official announcement)

Wednesday, August 09, 2006

Blogging science .. something like science

(via Open Reading frame and Uncertain Principles) This is what happens when you spend to much time in the lab. Dylan Stiles reports on his analysis of ... his own ear wax?! Creative post to say the least. :).

Tuesday, August 08, 2006

Identifying protein-protein interfaces

There were several interesting papers on protein interaction in the last week. For example, in PLoS Computational Biology, Kim et al described an improvement to a method that classifies interaction interfaces according to their geometry. The results of the analysis are available on their site SCOPPI.
It seems reasonable to believe that there is a limited number of protein interaction types (predicted to be around 10 thousand), much the same way that there is probably a limited number of folds used in nature. This database, along side others like the iPFAM database, provide templates on which to model other protein interactions with reasonable homology. As first proposed by Aloy and Russell, if we know that two proteins interact, for example with a yeast-two-hybrid experiment we might be able to use these databases to identity and model the interaction interface between the two proteins.

Here is an example of two complexes taken from the paper. The nodes and edges view hides the fact that RBP and RCC1 interact through different interfaces.

Although is has been very useful to look at protein networks as of bunch of nodes connected by edges for some analysis it would be much more informative to know what are the interacting interfaces.

The authors used the database to claim that:
- hub proteins interact with proteins using many distinct faces (what they actually show is that domains that interact with many different other domain types have more distint faces);
- two thirds of gene fusions conserve the binding orientation;
- the apparent poor conservation of interfaces is due to the diversity of interactions and partners (in my opinion it is more a suggestion that proof);
- the interfaces common to archae, bacteria and eukaryotes and mostly symmetric homo-dimers, suggesting that asymmetric and hetero interactions evolved from symmetric homo-dimers.

<speculation> Maybe if we could convert the current human interactome into more than nodes and edges we could try to see if some of disease causing polymorphisms can be explained by how they affect the interfaces. Maybe we could use this to do interaction KOs instead of whole proteins </speculation>

Saturday, August 05, 2006

PLoS ONE is accepting manuscripts - Update

(via PLoS blog and Open) The new PLoS ONE journal is now accepting manuscripts for review. They are still taking care of a few bugs and at this moments I could only use the site with Internet Explorer.
We can know have a look at the editorial board and the journal policies. There are some hints of how the user comments and ratings are going to work.

Most journals have some form of funneling, either by perceived impact or subject scope. It is going to be interesting to see what happens with PLoS ONE, given that there is no editorial selection on these criteria.

Update - It is actually working fine with Firefox1.5. When I was seeing it before the the page layout was misbehaving. Sorry for the confusion.

Friday, August 04, 2006

Meta blogging

Neil Saunders' blog as moved to a new home. Fabrice Jossinet is back blogging about RNA and bioinformatics in Propeller Twist.
If you are interested in RNA and microbiology go check out the new blog of Rosie Redfield. She runs a a microbiology lab at the University of British Columbia and will be blogging about their current research.

If you are interested in a better way to track the comments and responses to your comments in other blogs have a look at coComments. You can have an RSS feed and/or a box in your blog with your comments and responses to the comments that you wish to track.

Wednesday, August 02, 2006

Tangled Bank #59

The latest issue of Tangled Bank is up at Science and Reason. It is the first time I participate with a submission. If you are into physics the author of the blog, Charles Daney, is considering starting a physics carnival.

Tuesday, August 01, 2006

Bio::Blogs#2

The second edition of Bio::Blogs is up at Neil's blog. Go check it out and participate with your insightful comments :). There is a lot of conference blogging on this issue, a nice way to get updates on the conferences you might have missed.
I am happy to say that we have volunteers for the next two editions. Deepak offered to host for September 1st and Sandra Porter will host the October 1st edition.

Saturday, July 29, 2006

The likelihood that two proteins interact might depend on the proteins' age - part 2

Abstract
It has been previously shown [1] that S. cerevisiae proteins preferentially interact with proteins of the same estimated likely time of origin. Using a similar approach but focusing on a less broad evolutionary time span I observed that the likelihood for protein interactions depends on the proteins’ age. I had show this previously for the interactome of S. cerevisiae [2] and here I extend the analysis to show that the same is also observed for the interactome of H. sapiens. Importantly the observation does not depend on the experimental method used since removing the yeast-two-hybrid interactions does not alter the result.

Methods and Results
Protein-protein interactions for H.sapiens were obtained from the Human Protein Reference database and from two high-throughput studies excluding any interactions derived from protein complexes. I considered only proteins that were represented in this interactome (i.e. with one or more interactions).
As before I created groups of H. sapiens proteins with different average age using the reciprocal best blast hit method to determine the most likely ortholog in eleven other eukaryotic species (see figure 1 for species names). For a more detailed description of the group selection and the construction of the phylogenetic tree please see the previous post [2].
It is important to note that the placement of C. familiaris does not correspond with other published phylogenetic trees it might be due to the proteins selected for the tree construction. I should consider using different combinations of ancestral proteins to check the robustness of the tree.

In table 1 we can see the likelihood for protein interactions to occur within the ancestral proteins of group A and between the ancestral proteins and other groups of decreasing average age. As published by Qin et al. and as I had observed before for S. cerevisiae, the interactions within groups of the same age (group A) are more likely than between groups of proteins of different times of origin. Also, the likelihood for a protein to interact with an ancestral protein depends on the age of this protein. Confirming the pervious observation that the younger the protein is the less likely it is to interact with an ancestral protein.

I redid the analysis excluding yeast-two-hybrid interactions from the dataset. As it can be see in table 2, the results are qualitatively the same. There is a small increase in the likelihood of interaction with the ancestral proteins for the youngest group (highlighted in red in table 2) that is likely due to lack of data.


Caveats and possible continuations

I still have to test the statistical significance of these observations and control for possible other effects like protein size and protein expression that could explain these results.
I am interested in continuing this further as an open project. Fallowing the suggestion of Roland Krause I will soon start a wiki page to dump the data bits accumulated for open discussion. Hopefully more people will join in and maybe we can together shape up a small communication.

[1]Qin H, Lu HH, Wu WB, Li WH. Evolution of the yeast protein interaction network. Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12820-4. Epub 2003 Oct 13
[2]Beltrao. P The likelihood that two proteins interact might depend on the proteins' age Blog post

Friday, July 28, 2006

Binding specificity and complexity

There is a paper out in PNAS about the distribution of free energy of binding for the yeast-two-hybrid datasets. Although I still have to dig into the model they used I found the result quite interesting. They observe that the average binding energy decreases with cellular complexity.
They have some sentences in there that made my hairs stand like: "more evolved organisms have weaker binary protein-protein binding". What does "more evolved" mean ? Also on figure 4 of the paper they plot miu (a parameter related to the average binding energy) over divergence times without saying what species they are comparing.

This result fits well with another paper published a while ago in PLoS Comp Bio about protein family expansions and complexity. Christine Vogel and Cyrus Chothia show (among other things) what protein domains expansion best correlate with complexity. They used cell numbers as a proxy for species complexity. If you look at the top of the list (in table 2) you can find several of the peptide binding domains, know to be of low specificity, given that they do not require a folded structure to interact with.

What I would like to know is the correlation between binding affinity and binding specificity. For example SH2 domains bind much more tightly than SH3 domains although they are both not very specific binding domains. Maybe in general it could be said that average lower binding affinities correspond to lower average binding specificity.

Why would complexity correlate with binding specificity ? I think one important factor is cellular size. An increase is size has allowed for exploration of spacial factors in determining cellular response. Specificity of binding in the real cell (not in binary assays) is determined also by localization at sub cellular structures.

One practical reminder coming from this is that even if we have the perfect method to determine biophysical binding specificity we are still going to get poor results if we cannot predict all other components that will determine if the two proteins will bind or not (i.e localization, expression).

TOPAZ and PLoS ONE

According to the PLoS blog the new PLoS ONE will be accepting submissions soon. I guess they will at the same time release the TOPAZ system that will likely be available here.

"TOPAZ will serve the rapidly growing demand for sophisticated tools and resources to read and use the scientific and medical literature, allowing scholarly publishers, societies, universities, and research communities to publish open access journals economically and efficiently."


Sunday, July 23, 2006

Opening up the scientific process

During my stay at the EMBL, for the past couple of years, it already happened more than once that people I know have been scooped. This simple means that all the hard work that they have been doing was already done by someone else that manage to publish it a bit sooner and therefore limited severely the usefulness of their discoveries. Very few journals are interested in publishing research that merely confirms other published results.

From talking to other people, I have come to accept that scooping is a part of science. There is no other possible conclusion from this but to accept that the scientific process is very flawed. We should not be wasting resources literally racing with each other to be the first person to discover something. When you try to explain to non-scientist, that it is very common to have 3 or 4 labs doing exactly the same thing they usually have a hard time integrating this with their perception of science as the pursue of knowledge trough collaboration.
I am probably naïve given that I am only doing this for a couple of years but I don’t pretend to say that we do not need competition in science. We need to keep each other in check exactly because lack of competition leads to waste of resources. I would argue however that right now the scientific process is creating competition at wrong levels decreasing the potential productivity.

So how do we work and what do we aim to produce? We are in the business of producing manuscripts accepted in peer reviewed journals. To have competition there most be a scarce element. In our case the limited element is the attention of fellow scientist. Given that scientist’s attention is scarce we all compete for the limited number of time that researchers have to read papers every week. So the good news is that the system tends to give credit to high quality manuscripts. This means that research projects and ongoing results should be absolutely confidential and everything should be focused in getting that Science or Nature paper.
I found a beautiful drawing of an iceberg (used here with permission from the author, David Fierstein) that I think illustrates the problem we have today by focusing the competition on the manuscripts. Only a small fraction of the research process is in view.


Wouldn’t it be great if we could find a way to make most of the scientific process public but at the same time guaranty some level of competition? What I think we could do would be to define steps in the process that we could say are independent, which can work as modules. Here I mean module in the sense of a black box with inputs and outputs that we wire together without caring too much on how the internals of the boxes work. I am thinking these days about these modules and here is a first draft of what this could look like:


The data streams would be, as the name suggests, a public view of the data being produced by a group or individual researcher. Blogs are a simple way this could be achieved today (see for example this blog). The manuscripts could be built in wikis by selection of relevant data bits from the streams that fit together to answer an interesting question. This is where I propose that the competition would come in. Only those relevant bits of data that better answer the question would be used. The authors of the manuscript would be all those that contributed data bits or in some other way contributed for the manuscript creation. In this way all the data would be public and still a healthy level of competition would be maintained.
The rest of the process could go on in public view. Versions of the manuscript deemed stable could be deposited in a pre-print server and comments and peer review would commence. Latter there could still be another step of competition to get the paper formally accepted in a journal.

One advantage of this is that it is not a revolution of the scientific process. People could still work in their normal research environment closed within their research groups. This is just a model of how we could extend the system to make it mostly open and public. The technologies are all here: structured blogging for the data streams, wikis for the manuscripts and online communities to drive the research agendas.

I think it is important to view the scientific process as a group of modules also because it allows us latter to think of different ways to wire the modules together. Increasing the modularity should permit us to innovate. For example we can latter think of ways that the data streams are brought together to answer questions, etc.


Friday, July 21, 2006

Bio::Blogs #2 - call for submissions

(via Nodalpoint) This is just a quick reminder that we have 10 days to submit links to the second edition of Bio::Blogs. You can send your suggestions to bioblogs {at} gmail.com. Also if you wish to host future editions send in a quick email with your name and link to your blog to the same email address.

Monday, July 17, 2006

Conference on Systems Biology of Mammalian Cells

There was a Systems Biology conference here in Heidelberg last week. For those interested the recorded talks are now available on their site. There is a lot of interesting things about the behavior of network motifs and about network modeling.

Sunday, July 16, 2006

Blog changes

Notes from the Biomass is back again in a new website. I was cleaning the links on the blog to better reflect what I am actually reading and while I was at it I changed the template. It looks better in IE than in Firefox but I really don't have the time nor the ability to work on a good design.

Tuesday, July 11, 2006

Defrag my life

I am taking the week to visit my former lab in Aveiro, Portugal where I spent one year trying to understand how a codon reassignment occurred in the evolutionary past of C. albicans. This was where I first got into Perl and the wonders of comparative genomics.

It brings back a lot of memories every time I come back to one of the cities I lived in before (6 cities and counting) and I sometimes wonder if it is really necessary for scientists to live such fragmented lives.

reboot, restart, new program.

The regular programming will return soon :).

Tuesday, July 04, 2006

Re: The ninth wave

I usually reed Gregory A Petsko' comments and editorials in Genome Biology that are unfortunately only available with subscription. In the last edition of the journal he wrote a comment entitled "The ninth wave". I have lived most of my life 10min away from the Atlantic ocean and at least to my recollection we used to talk about the 7th wave not the ninth as the biggest wave in a set of waves, but this it not the point :).
Petsko argues that the increase of free access to information on the web and of computer savvy investigators presents a clear danger of a flood of useless correlations hinting at potential discoveries never followed by careful experimental work:
Computational analysis of someone else's data, on the other hand, always produces results, and all too often no one but the cognoscenti can tell if these results mean anything.

This reminded me of a review I read recently from Andy Clark (via Evolgen). Andy Clark talks about the huge increase of researchers in comparative genomics:
...one of its worst disasters is that it has created a hoard of genomics investigators who think that evolutionary biology is just fun, speculative story telling. Sadly, much of the scientific publication industry seems to respond to the herd as much as it does to scientific rigor, and so we have a bit of a mess on our hands.

I have a feeling that this is the opinion of a lot of researchers. There is this generalized consensus that people working on computational biology have it easy. Sitting at the computer all day, inventing correlations with other people's data.
Maybe some people feel this way because it is relatively fast to go from idea to result using computers if you have in a mind clearly what you want to test while the experimental work certainly takes longer.
Why should I re-do the experimental work if I can answer a question that I think is interesting using available information ? I should be criticized if I try to overinterpret the results, if the methods used are not appropriate or if the question is not relevant but I should not be criticized for looking for an answer the fastest way I can.

Monday, July 03, 2006

Journal policies on preprint servers (2)

Recently I did a survey on the different journal policies regarding preprint servers. I am interested in this because I feel it is important to separate the peer review process from the time-stamping (submission) of a scientific communication. Establishing this separation allows for exploration of alternative and parallel ways of determining the value of a scientific communication. This is only possible if journals accept manuscripts previously deposited in pre-print servers.
Today I received the answer from Bioinformatics:
"The Executive Editors have advised that we will allow authors to submit manuscripts to a preprint archive."


If you also think that this model, already very established in physics and maths, is useful you can also sent some mails to your journals of interest to enquire about their policies. If enough authors voice their interest there will be more journals accepting manuscripts from pre-print servers.
I think we are now lacking a biomedical preprint server. The Genome Biology journal served until early this year also as a preprint server but they discontinued this practice. Maybe arxiv could expand to include biomedical manuscripts (they already accept quantitative biology manuscripts) .

Saturday, July 01, 2006

Bio::Blogs # 1

An editorial of sorts

Welcome to the first edition of Bio::Blogs, a blog carnival covering all subjects related to bioinformatics and computational biology. The main objectives of Bio::Blogs are, in my opinion, to help nit together the bioinformatics blogging community and to showcase some interesting posts on these subjects to other communities. Hopefully it will serve as incentive for other people in the area to start their own blogs and to join in the conversation.

I get to host this edition and I decided to format it more or less like a journal with three sections:1) Conference reports; 2) Primers and reviews; 3) Blog articles. I think this reflects also my opinion on what could be a future role of these carnivals, to serve as a path for certification of scientific content parallel to the current scientific journals.

Given that there were so few submissions I added some links myself. Hopefully in the next editions we can get some more publicity and participation :). Talking about future editions, the second edition of Bio::Blogs will be hosted by Neil and we have now a full month to make something up in our blogs and submit the link to bioblogs{at}gmail{dot}com.


Conference Reports
I selected a blog post from Alf describing what was discussed in a recent conference dedicated to Data Webs. There is a lot of information about potential ways to deal with the increase of data submitted all over the web in many different formats. I remember seeing the advert for this conference and I was intrigued to see Philip Bourne, the editor-in-chief of PLoS Computational Biology, among the speakers. I see know that he is involved in publishing tools under development in PLoS.

Primers & Reviews
Stew from Flags and Lollipops sent in this link to a review on the use of bioinformatics to hunt for disease related genes. He highlights a series of tools and methods that can be used to prioritize candidate genes for experimental validation.

Neil, the next host of Bio::Blogs spent some time with the BioPerl package called Bio::Graphics. He dedicated a blog entry to explain how to create graphics for your results with this package. He gives examples on how to make graphic representations of sequences mapped with blast hits and phosphorylation sites.

Chris, a usual around Nodalpoint, nominated a post in Evolgen:
Evolgen has an interesting post about the relative importance (and interest in) cis and trans acting genetic variation in evo-devo. A lot of (computational) energy has thus far been expended in finding regulatory motifs close to genes (ie, within promoter regions), and conserved elements in non-coding sequences. Rather predictably, cis-acting variants have received the lion's share of attention, probably because they present a more tractable problem. The post deals with work from the evo-devo and comparative genomics fields, but these problems have also been attacked from within-species variation perspectives, particularly the genetics of gene expression. But that's next month's post...

Blog articles
I get to link to my last post. I present some very preliminary results on the influence of protein age on the likelihood of protein-protein interactions. Have fun pointing out all the likely flaws in reasoning and hopefully useful ways to build on it.

To wrap things up here is an announcement by Pierre of a possibly useful applet implementing a Genetic Programming Algorithm. If you ever wanted to play around with genetic programming you can have a go with his applet.


That is it for this month. It is a short Bio::Blogs but I hope you find some of these things useful. Don’t forget to submit the links for the next edition before the end of July. Neil will take up the editorial role for #2 in his blog. If you know of a nice symbol that we might use for Bio::Blogs sent it in as well.

The likelihood that two proteins interact might depend on the proteins' age

Abstract
It has been previously shown[1] that S. cerevisiae proteins preferentially interact with proteins of the same estimated likely time of origin. Using a similar approach but focusing on a less broad evolutionary time span I observed that the likelihood for protein interactions depends on the proteins’ age.

Methods and Results
Protein-protein interactions for S. cerevisiae were obtained from BIND, excluding any interactions derived from protein complexes. I considered only proteins that were represented in this interactome (i.e. with one or more interactions).
In order to create groups of S. cerevisiae proteins with different average age I used the reciprocal best blast hit method to determine the most likely ortholog in eleven other yeast species (see figure 1 for species names).

S. cerevisiae proteins with orthologs in all species were considered to be ancestral proteins and were grouped into group A. To obtain groups of proteins with decreasing average age of origin, S. cerevisiae proteins were selected according to the absence of identifiable orthologs in other species (see figure 1). It is important to note that these groups of decreasing average protein age are overlapping. Group F is contained in E , both are contained in D and so forth. I could have selected non overlapping groups of proteins with decreasing time of origin but the lower numbers obtained might in a latter stage make statistical analysis more difficult.
The phylogenetic tree in figure 1 (obtained with MEGA 3.1) is a neighbourhood joining tree obtained by concatenating 10 proteins from the ancestral group A. I did it mostly to avoid copyrighted images and too have a graphical representation of the species divergence.
To determine the effect of protein age on the likelihood of interaction with ancestral proteins I counted the number of interactions between group A and the other groups of proteins (see table 1).

From the data it is possible to observe that protein-interactions within groups (within group A) is more likely than protein-interactions between groups. This is in agreement with the results from Qin et al.[1]. Also the likelihood for a protein to interact with an ancestral protein depends on the age of this protein. This simple analysis suggests that the younger the protein is the less likely it is to interact with an ancestral protein.
One possible use of this observation, if it holds to further scrutiny, would be to use the likely time of origin of the proteins as information to include in protein-protein prediction algorithms.

Caveats and possible continuations
The protein-protein interactions used here also contain the high-throughput studies and therefore the interactome used should be considered with caution. I might redo this analysis with a recent set of interactions compiled from the literature[2] but this will also introduce some bias into the interactome.
I should do some statistical analysis to determine if the differences observed are at all significant. If the differences are significant I should try to correlate the likelihood of interactions with a quantitative measure like average protein identity.

References
[1]Qin H, Lu HH, Wu WB, Li WH. Evolution of the yeast protein interaction network. Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12820-4. Epub 2003 Oct 13
[2]Reguly T, Breitkreutz A, Boucher L, et al. Comprehensive curation and analysis of global interaction networks in Saccharomyces cerevisiae. J Biol. 2006 Jun 8;5(4):11 [Epub ahead of print]

Sunday, June 25, 2006

Quick links

I stumbled upon a new computational biology blog called Nature's Numbers, looks interesting.
From Science Blogs universe here is a list compiled by Coturnix of upcoming blog carnivals for the next few days. I also remind anyone reading that the deadline for submissions for bio::blogs is coming very soon so send in your links :).
Still in Science Blogs here is an introduction to information theory. I am getting interesting in this as a tool for computational biology but I have a lot to learn on the subject. Here are two papers I fished out that use information theory in biology.
Also, if you want to donate some money, go check out the donors choose challenge of several Science Bloggers. Seed will match the donations up to $10,000 making each donation potentially more useful.

Wednesday, June 21, 2006

Journal policies on preprint servers

I mentioned in a previous post that it would be interesting to separate the registration, which allows claims of precedence for a scholarly finding (the submission of a manuscript) from the certification, which establishes the validity of a registered scholarly claim (the peer review process).

This can only happen if journals accept that a manuscript submitted to a preprint server is different from a peer-review article and therefore it should not be considered as prior publication. So what do the journals currently say about preprint servers ? I looked around the different policies, sent some emails and compiled a this list:

Nature: yes but ...
Nature allows prior publication on recognised community preprint servers for review by other scientists in the field before formal submission to a journal. The details of the preprint server concerned and any accession numbers should be included in the cover letter accompanying submission of the manuscript to Nature. This policy does not extend to preprints available to the media or that are otherwise publicised before or during the submission and consideration process at Nature.


I enquired about this last part of their policy on the peer review forum and this was the response:
"We are aware that preprint servers such as ArXiv are available to the media, but as things stand we consider for publication, and publish, many papers that have been posted on it, and on other community preprint servers.As long as the authors have not actively sought out media coverage before submission and publication in Nature, we are happy to consider their work."


Nature Genetics/Nature Biotechnology: yes
(...)the presentation of results at scientific meetings (including the publication of abstracts) is acceptable, as is the deposition of unrefereed preprints in electronic archives.


PNAS: Yes!
"Preprints have a long and notable history in science, and it has been PNAS policy that they do not constitute prior publication. This is true whether an author hands copies of a manuscript to a few trusted colleagues or puts it on a publicly accessible web site for everyone to read, as is common now in parts of the physics community. The medium of distribution is not germane. A preprint is not considered a publication because it has not yet been formally reviewed and it is often not the final form of the paper. Indeed, a benefit of preprints is that feedback usually leads to an improved published paper or to no publication because of a revealed flaw. "


BMC Bioinformatics/BMC Biology/BMC Evolutionary Biology/BMC Genomics/BMC Genetics/Genome Biology: Yes
"Any manuscript or substantial parts of it submitted to the journal must not be under consideration by any other journal although it may have been deposited on a preprint server."


Molecular Systems Biology: Do you feel lucky ?
"Molecular Systems Biology reserves the right not to publish material that has already been pre-published (either in electronic or other media)."


Genome Research: No
"Submitted manuscripts must not be posted on any web site and are subject to press embargo."


Science: Do you feel lucky ?
"We will not consider any paper or component of a paper that has been published or is under consideration for publication elsewhere. Distribution on the Internet may be considered prior publication and may compromise the originality of the paper or submission. Please contact the editors with questions regarding allowable postings under this policy."


Cell: No ?
"Manuscripts are considered with the understanding that no part of the work has been published previously in print or electronic format and the paper is not under consideration by another publication or electronic medium."


PLoS - No clear policy information on the site about this but according to an email I got from PLoS they do consider for publication papers that have been submited in preprint servers. I hope they could make this clear in the policies they have available online.

Bioinformatics,Molecular Biology and Evolution - ??
"Authors wishing to deposit their paper in public or institutional repositories may deposit a link that provides free access to the paper, but must stipulate that public availability be delayed until 12 months after first online publication in the journal"

I sent emails to both journals but I only had an answer from MBE directing me to this policy common to the journals of the Oxford University Press.

In summary most journals I checked will consider papers that have been previously submited to preprint servers, so I might consider in the future to submit my own work to preprint servers before looking for a journal. Very few journals clearly refuse manuscripts that might be available in electronic form but a good number either have no clear policy or reserve the right to reject papers that are available online.

Monday, June 19, 2006

Mendel's Garden and Science Online Seminars

For those interested in evolution and genetics this is a good day. The first issue of Mendel's Garden is out with lots of interesting links. I particularly liked RPM's post on evolution of regulatory regions. I still think that evo-devo should focus a bit more on changes in protein interaction networks but more about that one of these days (hopefully :).

On a related note, Science started a series of online seminars with a primer on "Examining Natural Selection in Humans". This is a flash presentation with voice overs from the authors of a recent Science review on the same subject. I like this idea much more than the podcasts. I am not a big fan of podcasts because it is much faster to scan a text than it is to hear someone read it for you. At least with images there is more information and more appeal to spend some minutes listening to a presentation. The only thing I have against this Science Online Seminars initiative is that there is no RSS feed (I hope it is just a matter of time).

Friday, June 16, 2006

Bio::Blogs announcement

Bio::Blogs is a blog carnival covering all bioinformatics and computational biology subjects. Bio::Blogs is schedule to be a monthly edition to come out on the first day of every month. The deadline for submission is until the end of month. Submissions for the next release of Bio::Blogs and offers to host the next editions can be sent to:

I will be hosting the first issue of Bio::Blogs here and there will be a homepage to keep track of all of the editions.

For discussions relating Bio::Blogs visit the Nodalpoint forum entry.

Wednesday, June 14, 2006

SB2.0 webcast and other links

If you missed the Synthetic Biology 2.0 conference you can know watch the webcast here (via MainlyMartian).

Nature tech team over at Nascent continue with their productive stream of new products, including the release of Nature Network Boston and a new release of the Open Text Mining Interface. They even set up a webpage for us to keep up with all the activity here. They really look like a research group by know :) I wonder what will happen if they tried to publish some of this research... Open Text Mining Interface published by Nature in journal X.


Monday, June 12, 2006

PLoS blogs

Liz Allen and Chris Surridge just kicked off the new PLoS blogs. According to Liz the blogs will be used to discuss their "vision for scientific communication, with all of its potentials and obstacles". I thank both of them for the nice links to this blog :) and for engaging in conversation.

Chris Surridge details in his first post how news of PLoS One has been spreading through the blogs. I think this only happened because the ideas behind ONE do strike a chord with bloggers and I really hope their efforts are met with success and more people engage in scientific discussion and collaboration.