Open Access in a different way

Just for fun I though I could try this new cartoon website. This was I got out in a couple of minutes :). Take a wild guess of what publishers I was thinking about.



View in the toon webiste

Usage-based measurements of journal quality

(Via Nautilus) The UK Serials Group (UKSG) and the online usage metrics organization COUNTER are exploring the possibility of using online statistics as a metric to determine the impact of a journal. There is a user survey for anyone interested in giving their opinion on the subject. The survey aims to:
* Discover what you think about the measures that are currently used to assess the value of scholarly journals (notably impact factors)
* Gauge the potential for usage-based measures
* Provide an opportunity for you to suggest possible different, additional measures.

As a blogger I am used to the idea of tracking readership statistics. I was curious to have a look at how this statistics are tracked by the journals so I had a better look at this COUNTER initiative. According to the about page:
"Launched in March 2002, COUNTER (Counting Online Usage of Networked Electronic Resources) is an international initiative designed to serve librarians, publishers and intermediaries by facilitating the recording and exchange of online usage statistics."

If I understood the project, COUNTER aims to define standards for tracking of web statistics, to serve as a hub for gathering of this information from the publishers and to provide statistical analysis to interested parties (libraries). The publishers are responsible for gathering the usage data and producing the reports (according to COUNTER standards). In the website there is a list of publishers that are providing this information to the project.

It is possible to certify a publisher as COUNTER compliant by passing in a somewhat convoluted process where a library checks the publishers report for compliance with the standards. I can't help think that there should be more efficient ways of doing this. For bloggers it takes a second to include a few lines of code from one of many free online tracking services (i.e. sitemeter, Google Analytics, Feedburner) in the website, to get instant and free user statistics. In this case, the services have the responsibility to track the users and I have little or no control over the reported data. If online user statistics is to become a measure of journal impact (and I think it should), then I hope COUNTER licenses or creates technology similar to what is powering these services. It should be an independent tracking service providing the results, not the publishers.

Google Base API

While we are waiting for freebase to give us a chance to preview their service we can go ahead and try something that probably is very similar in spirit to freebase. Google Base has been up a long time but only recently have they opened it up for automatic access (see Google Base API). There are some restrictions but in the end we can think of it as a free online database that we can use remotely.

How easy is it to use ? If you like Java, C# or PHP you are in luck because they have client libraries to help you get started.

I also found this Google Base code in CPAN and decided to give this a try. After reading some of the information in the API website and having a look at the code it comes down to 3 main tasks: 1)authentication; 2)insert/delete/update; 3)query

Having installed the above mentioned CPAN module the authentication step is easy:

use WWW::Google::API::Base;
my $api_user = "username"; #Google user name
my $api_pass = "pass";     #Google pass
my $api_key =  "API_KEY";
            #any program using the API must get a key


my $gbase = WWW::Google::API::Base->new(
                             { auth_type => 'ProgrammaticLogin',
                               api_key   => $api_key,
                               api_user  => $api_user,
                               api_pass  => $api_pass  },
                                     { } );

That's it, $gbase is authorized to use that google account in Gbase.

Now to insert something useful in the database requires a bit more effort. The CPAN module comes with an example on how to insert recipes. I am not that great a cook so I created a new function in Base.pm that comes with the module. I called it insertSequence

sub insertSequence {
  my $self= shift;
  my $id = shift;
  my $seq_string = shift;
  my $seq_type = shift;
  my $spp = shift;
  my $l=shift;
  $self->client->ua->default_header('content-type', 
                                    'application/atom+xml');
  my $xml = <<EOF;

<?xml version='1.0'?>
<entry xmlns='http://www.w3.org/2005/Atom'
xmlns:g='http://base.google.com/ns/1.0'
xmlns:c='http://base.google.com/cns/1.0'>
<author>
<name>API insert</name>
</author>
<category scheme='http://www.google.com/type' term='googlebase.item'/>
<title type='text'>$id</title>
<content type='text'>$seq_string</content>
<g:item_type>sequence</g:item_type>
<g:spp type='text'>$spp</g:spp>
<g:length type='int' >$l</g:length >
<g:sequence_type type='text'>$seq_type</g:sequence_type>
</entry>

EOF
 
  my $insert_request = HTTP::Request->new( 
                        POST => 'http://www.google.com/base/feeds/items',
                                      $self->client->ua->default_headers,
                                      $xml);
  my $response;
  eval {
    $response = $self->client->do($insert_request);
  };
  if ($@) {
    my $error = $@;
    die $error;
  }
  my $atom = $response->content;
  my $entry = XML::Atom::Entry->new(\$atom);
  return $entry
}

The function takes in information on the sequence like the ID, the sequence string, type , species, length and creates and XML entry to submit to Google Base according to the specifications they provide in the website. In this case it will be an entry of type "sequence" (that is non standard for GBase). The only detail in this was that I could not get the sequence string into an item attribute of type text because there seams to be a size limit in these. This is why the sequence is in the description.

Ok, with this new function adding a sequence to the database is easy. After the authentication code as above we just need to do:

$gbase->insertSequence($simple ,$seq_str,
                           "protein","s.cerevisiae",$l);

After getting the information from somewhere to populate the variables. According to the Google API faq, there is a limit of 5 queries per second. In about 25 lines we can get a FASTA to GBase pipe. Here is an example of protein sequence in Gbase (it might get deleted in time).

Now I guess one of the interesting parts is that we can use Google to filter results using the Google Base query language. The CPAN module above already has a query tool. It is still very simple but it gets the results of a search into an ATOM object. Here is a query that returns items from S.cerevisiae that have length between 350 and 400:

my $new_id="http://www.google.com/base/feeds/items
        ?bq=[spp:s.cerevisiae][length(int) : 350..400]";
my $select_inserted_entry;
eval {
$select_inserted_entry =$gbase->select($new_id);
print $select_inserted_entry->as_xml;# The output in XML format
};
if ($@) {
my $e = $@;
die $e->status_line;  # HTTP::Response
}

I am not sure yet if these items are available to other users to query not the code that would do it. I think this example here only gets the items in my account. This was as far as I got with this. The last step would be to have an XML parser turn the returned ATOM object into something more useful.

BIND bought by Thomson Scientific

(via email and Open Access News) Thomson Scientific has acquired Unleashed Informatics the owner of, among other resources, the Biomolecular Interaction Network Database (BIND). In the email announcing the transaction it is claimed that the information will remain freely available:
"We will continue to provide you with open access to BOND — there will be
no change to the way you obtain and use the information you currently
have available — and we will work to ensure that the database remains knowledgeable, up-to-date and within the current high editorial standards."

Hopefully this will mean a better chance of survival for the database. BIND was created in 1998 under the Blueprint initiative, lead by Chris Hogue in Mount Sinai Hospital in Toronto. It is one of the best examples of the difficulties of financing scientific databases with current grant schemes. In 2005, having burned trough something like $25 million and with a staff of 68 curators, the database started having trouble securing funding to keep up with the costs. Finally in November 2005, the database stopped its curation activities and Unleashed Informatics (a spin-off also created by Chris Hogue) bought the rights to BIND and kept the data available.

In December 2006 Chris Hogue wrote in his blog:
"I am no longer employed by Mount Sinai Hospital and the Blueprint Initiative is now, obsolete. (...) For now I am self-employed as a writer and working part-time at Unleashed Informatics."

According to the public announcement posted in the site of Unleashed Informatics the management team of UI will now be part of Thomson Scientific, so it is possible that Chris Hogue is now heading Unleashed under the safer umbrella of Thomson.


Previous posts regarding BIND and database funding:
BIND database runs out of funding
BIND in the news
Stable scientific databases

Twitter - Reality streams

In the past couple of weeks there has been a lot of buzz around Twitter:
"A global community of friends and strangers answering one simple question: What are you doing?"

In Twitter the messages are limited to 140 characters and can be sent to everyone or to a restricted group of friends via phone, IM or the web. It is amazing to look at the landing page of Twitter and seeing all these messages flowing by of what random people are doing right now. Here is a random sample:
"Waaaahhhh... I want to go back to sleep, not go to work. Maybe the shower will help. less than 10 seconds"
"Just discovered Twitterholic (twitterholic.com), have to twitter more if I want to get on the list :P !! less than 20 seconds ago"
"was thinking of saying Hello World but has changed his mind less than 20 seconds ago"

I cannot find a good reason to even set up an account at Twitter. The only possible interesting use would be to keep in touch with friends and family but I have IM for that. I can use this blog to publish what I am thinking without the 140 character limitation. For once I agree with Nick Carr's view of this community application, it sounds a little bit narcissistic. As usual he puts his points across in a provocative manner:

"The great paradox of "social networking" is that it uses narcissism as the glue for "community." Being online means being alone, and being in an online community means being alone together. (...) As I walk down the street with thin white cords hanging from my ears, as I look at the display of khakis in the window of the Gap, as I sit in a Starbucks sipping a chai served up by a barista, I can't quite bring myself to believe that I'm real. But if I send out to a theoretical audience of my peers 140 characters of text saying that I'm walking down the street, looking in a shop window, drinking tea, suddenly I become real."

It seams like every time there is a technology that enables a more immediate communication between people, we jump to it (ex letters,emails,sms,IM).

Bioinformatic web scraping/mash-ups made easy with kapow

In bioinformatics it is common that we might need to use a web service multiple times. Ideally, whoever built the web service provided a way to automatically query the site via an API. Unfortunately, Lincoln Stein's dream of a bioinformatics nation is still not a reality. When there is no programmable interface available and the underlying database information is not available it's usually necessary to write some code to scape the content from the web service.

In come openKapow, a free tool to (easily) build and publish robots to turn any website into a real web service. To illustrate how easy it is to use it I have built a Kapow robot to get, for any human geneID, a list of orthologs (with species and IDs). I downloaded the robotmaker and tried it on the Ensembl database. To be fair Ensembl is probably one of the best bioinformatics resources with available API and easy data mining tools like Biomart. This was just to give an example.

You start the robot by defining the initial webpage and the service inputs and outputs. I decided to create a REST service that would take an Ensembl gene ID and output pairs of gene ID/species name. The robotmaker application is intuitive to use for anyone with a moderate experience with HTML. The robot is created by setting up the steps that should occur to transform the input into the desired output. For example, we have to define were the input should be entered by clicking on the search box:
From here there are a set of loops and conditional statements that you can include to get the list of orthologs:

We can run through the robot steps with a test input and debug it graphically. Once the robot is running it is possible to host it on the openKapow web page, apparently also free of charge. Here is the link for this simple robot (this link might go down in the future). Of course it is also possible to build new robots that use robots that are published on openKapow. Also this example uses a single webpage but it would be more interesting to use this to mash up different services together.

Systems and Synthetic biology RSS pipe

Here is the RSS feed for a Yahoo pipe combining and filtering papers mostly about synthetic and systems biology. There are three systems biology journals directly combined into the feed. Unfortunately I could not find the RSS feeds for IET Systems Biology so it is not included. On top of these are added selected papers from Nature tittles, PLoS titles, Cell, PNAS, Science and Genome Biology. The filtering is done using some typical key words that might be associated to Systems and Synthetic biology. Here is a simple illustration of how it works:
I still have to test the pipe for some time and tweak the filters, but it is enough to get an idea of the things that can be done with these pipes. Like the pipe before you can clone this and change the filters and journals as you like.

Community filtered journal RSS feeds


I was trying out Yahoo pipes today to see how much we can actually program with it. It has some loop functions and regex filters but otherwise it is currently a bit limited. One thing that it is very good for is to combine and filter RSS feeds. Imagine that you want to get all the papers of a journal (or a group of journals) but only if someone else has for some reason found them interesting. This was what I tried to do with this pipe. I piped the RSS feed for MSB through a Yahoo query restricted to Connotea or Citeulike and in return I get a feed for the papers that have been tagged by other people in these sites. The problem is that this relies on the yahoo search, so it has to wait for yahoo to crawl those sites before it identifies the a new tagged paper and it is also possible that the paper title is to ambiguous and therefore incorrectly matched.

To add/change the input journals copy the pipe from here and edit the top fetch box.
(disclamer: I am currently working for MSB)

Quick Links

Deepak recorded his first podcast. Even if I am not a big fan of podcasts, I found it interesting to hear. Maybe it could serve as platform for a radio version of his blog. The idea of doing interviews would be really nice. In general I prefer reading because I can do it much faster than listening. Next year, when I go back to doing more bench work I will probably try consuming podcast while working.

(Via Deepak, Roland, and Konrad) Freebase is a very promising new web service. For those who have heard about semantic web, it will look familiar. They want to organize data by allowing users to add metadata to the information stored on the site. This will be great for aggregation of content and data mining. For science it could serve as place to deposit and organize data for collaborative projects.

(Via BioHacking) Microsoft has announced the winners of the first award for computational challenges in Synthetic Biology. Six projects were awarded a total of $570,000 (USD) to develop tools for synthetic biology.

(Via Jason Stajich) My own favorite model organism database (SGD) has created a wiki for community annotation. Anyone interested in S. cerevisiae biology, methods, reagents and strains can go there and help populate the wiki.

Global Ocean Sampling Expedition - Update

(via Konrad and Jonathan Eisen) The first results of Craig Venter's boat trip are now packaged and presented in PLoS Biology. There is going to be a webcast today at 10:00 AM Eastern time, 15:00 GMT. I am still skeptic of the usefulness of such datasets. Right now I still think that metagenomics, with current analysis methods, looks more promising at a smaller scale, to analyze smaller bacterial communities were the impact of perturbing the bacterial community could be studied. Of course this can be just my naive view of someone that never actually did any work with these datasets. In any case, many groups are likely throwing a lot of computing power at making many more interesting findings from the data. Also, this is just the first part of the trip. The full voyage can be seen in their website. I wonder what they will do with the rest of the data.

Any concrete questions on metagenomics can be directed at the blogs of the experts :). Konrad works with metagenomics in the Bork group and Jonathan Eisen is one of the authors in some of the papers, so he might know a thing or two about this stuff.

Craig Venter might be a controversial figure but he has surely been one of the few that has so strongly generated enthusiasm in science. He has been involved in the sequencing race to finish the human genome draft, a great metagenomics sampling voyage around the world (inspired by the British Challenger expedition) and some initiatives on the personal genome and biofuel production. His actions are propagated in the media and bring biology closer to the people that pay for us to do this work.

(image adapted from Gross L (2007) Untapped Bounty: Sampling the Seas to Survey Microbial Biodiversity. PLoS Biol 5(3): e85 doi:10.1371/journal.pbio.0050085)

Update - The webcast mentioned above has started. It looks like a bit of marketing hype event. The fact that we need windows media player might scare some people away. There is an email address in the site to send in questions. I will try to liveblog it for a while.

14:18 GMT -A PLoS editor is up explaining why open access publication is such a good match to this work.
Many of genome papers are not freely available. Venter decided to publish in PLoS making not only the data but the papers describing them are available.

14:20 GMT - Venter is up again. It took them 6 months of peer review to get the papers trough so we should not confuse open access to easy access. 18 000 40 000 new species after 1 my of sequences from the Sargasso sea. The question was to continue sequencing Sargasso sea or going to other places. This why the the expedition was set up. Part of the motivation for the voyage was also to promote science to the main public. Some of the areas were they passed they had some political problems because they are contested by different countries. There is a very large divergence from site to site (but this we can read in the papers anyway).
He suggest it would be possible to tell were a ship came from by analyzing the microbial diversity in the boat. There is strong geographical preference for the light sensitivity for the foto-receptors. Another surprise was trying to map the diversity obtained in the voyage to known genomes. They could observed co-existence of organism with very large sequence diversity for the same species (not sure I got this right but it is in the main paper). New gene and protein families are being discovered in linear fashion and therefore we are still not near saturation.

14:30 - Introduction of the CAMERA database to host the data. Genomic and environmental on a big cluster, currently doing blasts . There are huge problems with a database of this size so they are (i think) making different copies of the database in the US.

14:40 - Venter is up again to answer Q&A. I'll end the liveblogging here.

Journal policies on picture copyright

When blogging about science papers it is usually very useful to use some of the published pictures. Unfortunately most science publishers still use very restrictive licenses that disallow the use of the published material. In most cases I would be interested in promoting the paper because I think it is interesting and worth spending some time writing a blog post on. Aside from helping me remember the paper by writing down a post it it useful for meta aggregation of opinions (see Postgenomic). Eventually we might get the direct opinion from scientist in each field about what is being published. So, in most cases, it is in the publishers interest that I take a picture from the paper to promote it. What are the journal policies on this issue ?

PLoS and BioMed Central:
These are most blogger friendly publishers, they publish on open licenses that allow the re-use of content including making derivate works as long as there is clear attribution to work. We are even free to make money from this content or from derivatives that we make with it. From a user point of view this is absolutely liberating. I can not only read these manuscripts but I can use their pictures to comment on them and I can even think of creatively combining their content with other works. An example of this is PLoS Two, a site to explore layouts created by Alf based on the content of PLoS ONE. Anyone could try to create a better website for a science journal based on the content of PLoS and BioMed Central.

PNAS:
On their page on Rights and Permissions we can read:

"Anyone may, without requesting permission, use original figures or tables published in PNAS for noncommercial and educational use (i.e., in a review article, in a book that is not for sale) provided that the original source and copyright notice are cited."

It does not really say anything about blogs but I think it would be safe to take a picture from a PNAS paper and blogging about it since I don't run any adds and it would clearly be for educational use.

Science:
When you click on an image in a paper we see below the picture:

"You may download the image(s) above for non-profit educational presentation use only, provided no modifications are made to the content. Any use, publication, or distribution of the image(s) beyond that permitted in the sentence above or beyond that allowed by the "Fair Use" limitations (sections 107 and 108) of the US Copyright law requires the prior written permission of AAAS."

Again, they make no mention of the online world. They are probably talking about using the picture in a public presentation in a conference for example. How would this relate to a blog post? To make sure it would be necessary to send fill out this form asking for permission, but I think it would take some time to get a reply. I will get back to the fair use issue below.

Nature:
In their page on rights and permission they write:

"Permission can be obtained for re-use of portions of material - ranging from a single figure to a whole paper - in books, journals/magazines, newsletters, theses/dissertations, classroom materials/academic course packs, academic conference materials, training materials (including continuing medical education), promotional materials, and web sites. Some permission requests can be granted free of charge, others carry a fee."

So it is possible to get permission to use their content but it has to be obtained on a case by case basis and it might cost money. I tried getting permissions to use pictures from a Nature Biotech paper for a educational website and it cost nothing for 1 to 3 pictures. Above that it starts costing 150 dollars. It also costs nothing to get permission to include less than 400 words but above that we have to pay. The procedure is very straightforward and can be done in a minute.

Oxford Journals (including Bioinformatics)
Permissions of Oxford Journals is handled by the Copyright Clearance Center. We have to request permission also on a case by case basis:

* Simply visit the Oxford Journals homepage and locate the content you wish to reuse by searching, or navigating the journal's archive.
* Click on "Request Permissions" within the table of contents and/or in the "services" section of the article’s abstract to open the following page:
* Select the way you would like to reuse the content
* Create an account or log in to your existing account
* Accept the terms and conditions and permission will be granted

The gave it a try with a bioinformatics paper and at least to get permission to use 1 to 4 pictures on a non-commercial e-book it would not cost anything. There was no option for a blog post but I think it is sufficiently similar to an e-book. Five or more pictures require payment to obtain permission. Again, the procedure is fast and straightforward.


This is not an exhaustive search but overall I think we are safe in using one or two pictures in a blog post (on non commercial blogs) to talk about a paper. Even if there is no clear way of obtaining permission we might able to claim that this is fair use. According to the US copyright law fair use is:

Notwithstanding the provisions of sections 106 and 106A, the fair use of a copyrighted work, including such use by reproduction in copies or phonorecords or by any other means specified by that section, for purposes such as criticism, comment, news reporting, teaching (including multiple copies for classroom use), scholarship, or research, is not an infringement of copyright. In determining whether the use made of a work in any particular case is a fair use the factors to be considered shall include —
(1) the purpose and character of the use, including whether such use is of a commercial nature or is for nonprofit educational purposes;
(2) the nature of the copyrighted work;
(3) the amount and substantiality of the portion used in relation to the copyrighted work as a whole; and
(4) the effect of the use upon the potential market for or value of the copyrighted work.
The fact that a work is unpublished shall not itself bar a finding of fair use if such finding is made upon consideration of all the above factors.

Unfortunately this is absolutely vague but what publisher in their right mind would even try to sue a poor blogger when there might be a case for fair use. According to Postgenomic there has been around 2500 science blog posts a week. Even if only a fraction are talking about actual science papers it would be nice to have clear policies from the publishers on the subject.

The value of a reader in an author pays publishing model

In many respects the changes in online communication and collaboration have been the leading edge of what latter is tested by the scientific community. I regard sites like Digg, del.icio.us, blogger and other related sites as experiments from witch we can learn about using the internet to make scientific communication and collaboration more efficient. In that context I think there might be an interesting analogy between a study (PDF version), pointed by Nick Carr discussing the value of a free costumer.

In this study the authors created a model to analyze the "profitability of costumers in a networked setting". One example of this type of setting are the auction houses were two distinct users (buyers and sellers) exist. Buyers do not pay anything to the auction houses but provide an obvious value that is, as they say, difficult to quantify. In their analysis they estimated that in this type of network setting the value of buyer is actually higher than the value of the seller (the one that actually pays to use the service).

How might this relate to scientific publishing? In the current model of a journal like PLoS or similar journals there are two very obvious "costumers", the author (that pays to have the article distributed) and the readers, that pay nothing to get access to the journal. The other main publishing model is the opposite, the authors pay nothing (or much less at least) and the readers have to pay to access the journal. It might be that in the different models the publishers might have to direct their efforts differently. In a journal like PLoS ONE were the quality of the service might actually improve with the participation of the readers (annotations/discussions) I would think that the value of the reader is likely much higher than the paying costumer (authors). It would interesting to read a similar study directed at the economics of scientific publishing.

OpenWetWare:Reviews

Jason Kelly opened up a page in OpenWetWare for discussion of wiki reviews. Writing a review on the progress of a field could be the most obvious use of collaborative efforts. The reviews could be continually updated and periodic versions could be frozen and submitted to a more conventional repository.

Jason suggests that one way to kick start the process would be to wikify a review published already with an open license and let people update it. OpenWetWare has now over 2000 registered users and continues to grow as probably the best example of online collaborations in science.

If you have ideas about how to implement wiki reviews, or simple want to start writing one, head over there and give it a try.

Blogroll update

I finally got around to setting up the blogroll after updating the blog to the new blogger version. I have put on the right side most of the things that I am enjoying reading at the moment, separated in four sections:
Bioinformatics
Biotech & Drug Discovery
Evolution & Genomics
Publishing & General Science

One novelty in the list is the BioMed Central blog. They are now the third publishing house with some sort of official blog. Nature was the first and at least Nascent, Nautilus and Peer-to-peer provide mostly useful information and a way to interact with Nature services. Some other Nature blogs are not as interesting, in part because of a disturbing habit of using blog posts has a mirror for the table of contents of the journal.

Bio::Blogs #8


Editorial musings

Welcome to the eight edition of the bioinformatics blog journal Bio::Blogs. The archive from previous months can be found at bioblogs.wordpress.com. When this carnival was started, more than eight months ago, it had the primary objective to serve as sort of display for some of the best bioinformatics blog posts on the web and to create incentives for other people to promote their blogs and join in the conversation.

Looking back at the past Bio::Blogs editions I would like to think that we have manage to come with with many interesting posts about bioinformatic conferences, tools and useful computational tips like the DNA analysis series by Sandra Porter (I,II,III,IV,V,VI). Bio::Blogs has also been use to promote tools that have been published in blogs like the Genetic Programming Applet from Pierre and research like the correlation between protein-interaction likelihood and protein age (I and II) that I worked on.

Not everything went as I would hope. The submissions to Bio::Blogs have not picked up as I would expect. Some of this can be explained by poor promotion of my part but it is also due to the small size of the bioinformatics blogging community. In any case I think it is worth maintaining Bio::Blogs up and running for some more time before thinking about stopping this experiment.

In this edition a PDF version of all the posts has been created for anyone interested in downloading, printing and reading some fine posts over coffee or tea. Leave comments or send an email (bioblogs at gmail.com) with your thoughts/ideas for the continuation of this blog journal.I think this printed version also gives a more concrete impression of the potential of blogging for scientific communication.

News and Views

GrrlScientist submitted a report on a recent Science paper describing how moths use their antennae to help them stabilize their flight. Apart from some nasty experiments were they authors removed and glued parts of the antenna the work features some interesting neurophysiology analysis used to characterize the sensitivity of the antennae.

From my blog I picked an entry on network reconstruction. I think the increasing amounts of omics data should be better explored than it currently is and network reconstruction methods are a very good way of achieving this. In this paper, Jason Ernst and colleagues used expression data to reconstruct dynamic transcription regulatory interactions. I will try to continue blogging about the topic in future posts.

Comentaries

PLoS ONE was launched about two months ago and it has produced so far an amazing stream of publications. However the initially proposed goal of generating discussions online to promote post-publication reviews as been lagging. Stew and Alf wrote two commentaries (summited by Greg) regarding the progress of PLoS ONE. They both discuss the current lack of infrastructures to stimulate the online discussions at the PLoS ONE site. Stew goes even further by providing to anyone interested a nice Gresemonkey script to add blog comments to the PLoS ONE papers. I hope Chris Surridge and the rest of the PLoS ONE team start deploying soon some of the tools that they have talked about in their blog. They need to make ONE feel like home, a place were a community of people can discuss their papers.

From Deepak we have a post dedicated to what he dubs EcoInformatics. The importance of using computational methods to analyze ecological changes from the molecules to the ecosystems. The problems range from data access to data management and analysis. The complexity and the different scales of organization (i.e. molecules, environment, ecosystems, disease) make this a very promising field for computational biologists.

From ecological changes we move on to human evolution. Phil tries to introduce the possibility of humanity using technology to improve itself. Having a strong interest myself in synthetic biology and man-machine interfaces I would say that we are still far away from having such control. It is nevertheless useful to discuss the implications of emerging technologies to better prepare for the possible changes.

Reviews and tips

I start this section with a post from a bran-new bioinformatics blog called Bioinformatics Zen. Michael Barton submitted his post on useful tips to get organized as a dry lab scientist. I agree with most of his suggestions. I have try to use slightly fancier methods of organizing my work using project managing tools but I end up returning to a more straightforward folder based approach as well.

Neil Saunders sent in a nice tutorial on building AJAX pages for bioinformatics. It is a very well explained introduction with annotated code. If you were ever interested in learning the basics of AJAX but never invested time in it, here is a good chance to try it.

Craig Venter in Colbert Report

(via Drew Endy in SynBio discuss list) Here is mister Craig Venter in Colbert Report promoting synthetic biology and the personal genome (in a funny way).



Let's hope that Synthetic Biology does not get over hyped. The public might start reacting negatively to these technologies if they grow too fast or if they don't deliver what they promise.

Bio::Blogs #8

The eighth edition of Bio::Blogs is coming up soon. It is going to be published here on Public Rambling tomorrow night. I almost forgot that this month is shorter than usual :). There are currently 3 submissions sent in. Pick something from your blogs that is bioinformatic related and sent it in (bioblogs at gmail) or leave the link in the comments. Please also let me know if you mind that I create a PDF file including your submission for offline reading. If you don;t have a blog start one and let me know or just send in a link to something that you particularly liked.

The future impact of genome synthesis

The synthesis blog pointed to a detailed report discussing the economical importance of impending advances in biological engineering. The study, supported by DOE, DuPont Corporation and The Berkley Nanosciences Nanoengineering Institute tries to cover the main driving forces for biotechnology innovation, it's possible future applications and economical impact. The last chapter is dedicated to envisioning future scenarios for synthetic biology based on different assumptions about important factors that could determine the progress of this technology.

While the scenarios described in the end of the report might be useful to track the speed and mode of evolution of this emerging technology, the most relevant section for life scientists is arguably the one discussing possible applications of genome synthesis.
There are three main applications listed:
Chemicals: Engineering new production pathways and creating new products
Energy: Opening new biological routes for energy transformation
Synthetic Vaccines: Opportunities for rapid-response biosecurity

The best examples of synthetic biology research have consisted up to now mostly of simple toy examples. Usually simple circuits are created and studied to detail but few have obvious immediate practical applications. Are we currently at the inflection point, were synthetic biology research will produce more practical applications or is the complexity of living systems still too large a barrier ?

One example of the use of synthetic biology in chemical production is the work of Dae-Kyun Ro and colleagues in the Keasling lab (free PDF). They re-engineered S. cerevisiae to produce artemisinic acid, a precursor of the malaria drug Artemisinin.

Keasling is also one of the researchers involved in the Helios project. An effort directed at developing technology for solar fuel generation (in the form of biofuel). The project is also headed by Nobel prize laureate Steve Chu that explains the project in this video presentation.

Traveling around (Boston, San Francisco)

I have been traveling during the past week. I have been in Boston and I am now in San Francisco (labs: Marc Vidal, Wendel Lim, Adam Arkin).It would be interesting to be able to talk about some of the nice projects I have heard about but I guess it is really not up to me to make this public. Some of it is on their webpages. That leaves very little to say about the trip in respect to science. So instead, here is a picture I took in San Francisco :)


I am looking for a place to start a postdoc after the summer time. Even if I don't move to the states it is very unlikely that I will stay in Germany. This will be my 3rd country and 7th city. It is funny that so many of the grants that are currently available in Europe for postdocs are incentives to increase mobility. Isn't it time to also create some incentives to settling down ? I am 28 and this will be my first postdoc but eventually I will get tired of moving around. I hope by then it will be easier to stay.

in sillico network reconstruction (using expression data)

In my last post I commented on a paper that tried to find the best mathematical model for a cellular pathway. In that paper they used information on known and predicted protein interactions. This time I want to mention a paper, published in Nature Mol. Systems Biology, that attempts to reconstruct gene regulatory networks from gene expression data and Chip-chip data.

The authors were interested in determining how/when transcription factors regulate their target genes over time. One novelty introduced in this work was the focus on bifurcation events in gene expression. They tried to look for cases where a groups of genes clearly bifurcated into two groups at a particular time point. Combining these patterns of bifurcation with experimental binding data for transcription factors they tried to predict what transcription factors regulate these group of genes. There is a simple example shown in figure 1, reproduced below.


In this toy example there is a bifurcation event at 1 h and another at the 2h time point. All of the genes are assigned to a gene expression path. In this case, the red genes are those that are very likely to show a down regulation in between the 1st and 2nd hour and stay at the same level of expression from then on. Once the genes have been assigned it is possible to search for transcription factors that are significantly associate to each gene expression path. For example in this case, TF A is strongly associated to the pink trajectory. This means that many of the genes in the pink group have a known binding site for TF A in their promoter region.


To test their approach, the authors studied the amino-acid starvation in S. cerevisiae. In figure 2 they summarize the reconstructed dynamic map. The result is the association of TFs to groups of genes and the changes in expression of these genes over time during amino acid starvation.

One interesting finding from this map was that Ino4 activates a group of genes related to lipid metabolism starting at the 2h time point. Since Ino4 binding sites had only been profiled by Chip-chip in YPD media and not in a.a. starvation, this is a novel result obtained using their method.

To further test the significance of their observation they performed Chip-chip assays of Ino4 in amino acid starvation. They confirmed that Ino4 binds many more promoters during amino acid starvation as compared to synthetic complete glucose media. Out of 207 genes bound by Ino4 (specifically during AA starvation) 34 were also among the genes assigned to the Ino4 gene path obtained from their approach.

This results confirmed the usefulness of this computational approach to reconstruct gene regulatory networks from gene expression data and TF binding site information.
The authors then go on to study the regulation of other conditions.


For anyone curious enough about the method, this was done using Hidden Markov Models (see here for available primer on HMMs).