Monday, August 18, 2008

The DNA Network

The DNA Network

What’s on the web? (18 August 2008) [ScienceRoll]

Posted: 18 Aug 2008 04:11 PM CDT

The conference schedule of the Medicine 2.0: Social Networking and Web 2.0 Applications in Medicine and Health is up. The medical bloggers’ panel and my oral presentation both will take place on the first day.

  • Spectacular medical animations narrated in several languages at

  • A fantastic slideshow from Cynthia K. Russel about Enhancing Learning Outcomes with Online Activities and Virtual Worlds
  • The Experimantal Man Project: This is a new website that will be added to over the coming months. It will include data from author David Ewing Duncan’s tests covering his genes, environment, brain and body, along with commentary, analysis and musings about the usefulness and impact of this information on an individual human.

Web 2.0 and Medicine Course: First Part [ScienceRoll]

Posted: 18 Aug 2008 03:42 PM CDT

As you may remember, I will run the first medicine 2.0 course from this September at the University of Debrecen. Now I’m asking you to add your ideas and suggestions regarding the subjects. This time, we should focus on the first two weeks:

1st week:

  • What does web 2.0 mean? (the main concept and idea of web 2.0)
  • Web 2.0 in medicine: Introduction (my usual presentation, see below)

2nd week:

  • The medical blogosphere (why to blog; advantages; examples)
  • From the first comment to blog carnivals: Step by step (how to start and maintain a medical blog)

If you have anything in mind, any websites or services I should talk about in my presentations, please let me know.

I will feature this experiment in the first slideshow as an example about how web 2.0 works.

Power-up Your Restriction Screens [Bitesize Bio]

Posted: 18 Aug 2008 12:18 PM CDT

At the end of the day, all you want to know from a restriction screen is whether your insert is in the vector. But while the standard "chop out a fragment" approach favored by most researchers provides good information about the presence of the insert and its orientation, it only uses a portion of the potential power of a restriction screen.

It doesn't take much more work to set up a restriction screen that is more informative, allowing you to confirm a negative result and the identity of your vector, at the same time as checking for your insert. Here's a few ways you can soup-up your restriction digest.

1. To confirm negative results:
If you screen by cutting out your insert using the enzymes you cloned in with, but don't get any insert bands back it's difficult to know whether this is a negative clone or just a dirty prep that didn't digest properly. An alternative approach is to use restriction enzymes that cut in the vector itself and flank the multiple cloning site so that a negative result generates a fragment, but a positive clone will generate a bigger fragment.

2. To test positive results: If you want a quick test of whether your insert has actually been cloned in, a good approach is to chop out a fragment from the insert itself. This way you can simultaneously verify the presence of an insert and its identity. This can be especially useful if the cloning-in restriction sites have been damaged during cloning.

3. To confirm the integrity of the vector:
Vector deletions (thanks to E. coli) can occur in GC-rich regions, and star activity can delete portions of the vector on the 5` and 3` side of the cloning site during vector preparation (especially when vectors are not well prepared – see proper vector preparation). Restriction screens can be designed to digest on both sides of the multi-cloning site and at different positions around the vector so that the integrity of the vector can be confirmed. After all, we want the vector to work too!

Let us know your restriction digest tips in the comments.

MUST LISTEN: Robert Krulwich on Science for the Masses [The Daily Transcript]

Posted: 18 Aug 2008 10:31 AM CDT

Polarity, Diffusion, and Cellular Aging [Bitesize Bio]

Posted: 18 Aug 2008 08:56 AM CDT

Two recent articles that I came across clearly illustrate ways in which cellular asymmetry is both easily established by basic factors, and provide the basis for processes like cellular polarity and aging. One cannot claim with certainty what these findings in mathematical models and yeast, respectively, impart to our understanding of human health. But they do allow us to generally describe very basic rules for the operation of eukaryotic life.

In the first, Steven Altschuler and colleagues at the University of Texas SW demonstrated in a modeling study the spontaneous emergence of cell polarity. They demonstrate that chance recruitment of a given signaling molecule to sites at the cell’s membrane where it is already bound - a positive feedback - is sufficient to provide the basis for polarity, provided that the total pool of this molecule is small. When the number of molecules becomes too high, other biological mechanisms such as cytoskeleton-based transport are needed.

In the second article, Zhanna Shcheprova and coworkers in Zurich, Switzerland, illustrate a mechanism for asymmetric segregation of age during yeast budding. They show that a diffusion barrier develops in the nuclear envelope of the dividing yeast nucleus. The barrier prevents pre-existing nuclear pores and other membrane-associated proteins from moving into the bud.

This second article provides an excellent example of the spontaneous emergence of asymmetry/polarity, and an example of its function (i.e. cell aging). In this case though, cytoskeleton-based transport is replaced with compartmentalization - really a variation on transport.

And that’s really what the aging article shows - a variation on a biological “rule” that’s been uncovered. It could have turned out any number of ways, and now that it seems so patently obvious, it almost seems like a tautology. But it’s not. Polarity didn’t have to be generated by diffusion.

At the level of our basic building blocks, complex life changes such as aging, locamotion, and others, are becoming rather, well, simple.

Image: Figure 1 from Altschuler et al., Nature

  • Altschuler SJ, Angenent SB, Wang Y, Wu LF, Nature. 454:886-889 (14 Aug 2008)
  • Shcheprova Z, Baldi S, Frei SB, Gonnet G, Barral Y, Nature. 454:728-734 (7 Aug 2008)

Red-hot Alchemist [Sciencebase Science Blog]

Posted: 18 Aug 2008 07:00 AM CDT

Chilli PeppersIn my ChemWeb column, The Alchemist, this week:

Van Gogh was two-timing his canvas, the Alchemist learns this week, thanks to novel X-ray studies of a seemingly innocuous piece called Patch of Grass, which hides a woman’s face beneath its green and peasant landscape.

Professional wine tasters and vintners with a penchant for pepping up their plonk should have something new to worry about thanks to the development of an electronic tongue for detecting adulterated wines and those labeled with the wrong vintage.

In biochemistry, sex and sleep turn out to be inextricably entangled, at least in the world of the lab technician’s favorite nematode worm, Caenorhabditis elegans.

Traditional Chinese Medicine is heavily marketed despite a lack of clinical evidence of efficacy of many of the remedies. However, The Alchemist hears of a traditional remedy for allergy that, toxic components removed, could work to prevent life-threatening peanut allergy.

The world of red hot chili peppers wouldn’t be so hot if it were not for nibbling insects and a fungus that infects the chilis.

Finally, a million-dollar grant to get the blood pumping will for the next five years fund research into how the brain controls blood pressure and could eventually lead to new treatments for hypertension and cut deaths from cardiovascular disease.


Red-hot Alchemist

The New BRCA....this time its the Colon!!! [The Gene Sherpa: Personalized Medicine and You]

Posted: 18 Aug 2008 05:53 AM CDT

This is a fantastic review. I have been very careful trying to avoid hyping tests. I do this because we need validation and some evidence for use would be nice. The problem is that sometimes a test...

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SciFoo: scientific fireworks [The Seven Stones]

Posted: 18 Aug 2008 04:37 AM CDT

In his list of eight 'generative' values (Better Than Free), Kevin Kelly includes 'embodiment'–the actual physical realization of an item or event which could be otherwise freely distributed over the web. While we are all 'hyperlinked' on the Internet, the value of those unique qualities that cannot be generated or "copied" on the web is dramatically increased. The type of intense emulation and shared excitement sparked at the recent Science Foo Camp (SciFoo 2008), organized by Nature, Google and O'Reilly, gave a wonderful example of the unique value of direct human exchange during an exclusive event bringing together roughly 200 top scientists, 'geeks' and other technologists at the Googleplex in Mountain View, California.

SciFoo is a so-called 'unconference': there is no program or more precisely, as Timo Hannay explained during the opening of the conference, the attendees are the 'program'. The actual schedule was defined only on the first evening in a purposefully chaotic process by anyone who wished to organize a session on any topic. For the next two days, in a festival of parallel sessions, astrophysicists, 'googlers', technologists, molecular biologists, taxonomists, game designers, flying car constructors, publishers, thinkers and (some) dreamers discussed and exchanged ideas with great enthusiasm and a rare intensity and openness.

Needless to say that deciding which session to attend was close to impossible... In any case, I ended up following three types of talks: a series on systems biology related topic (data integration, machine learning, personal genomics, baroque structure of the transcribed genome), several (of many) sessions focused on the theme of open data/science and finally some more eclectic sessions (only from my standpoint, of course) on diverse topics such as the foundations of the concept of time in physics, on some demonstration of very simple yet powerful Python scripting exercises to analyze text and the potential of game design to harness our 'cognitive surplus'. I cannot possibly summarize all the talks, interactions and impressions gathered at this meeting, but here are a few subjective excerpts:

  • There were quite a few sessions on open science and open data. Ernst Hafen made a strong case for the need of a unique AuthorID that would help in tracking the multiple aspects of researchers' scientific activities. With regard to data, Google announced that a new service will soon be launched, Google Research Datasets, offering to host, for free, large datasets of any type. The service will allow inclusion of some minimal meta-data about the submitted datasets and will provide a mechanism to define a delay before the dataset is made publicly visible. This will probably become a very simple and convenient way for storing data (in particular if a useful API is developed), so convenient in fact, that we may have to be a little careful that it will not turn into a temptation to bypass the 'minimal information...' standards usually required by traditional public databases.
  • George Church provided an overview of the Personal Genome Project (PGP) and described the type of biological data that will be integrated with the genomic and genetic information collected from consenting PGP volunteers: analysis of the transcriptome of pluripotent stem cells derived from the subjects; sequence of the repertoire of recombined V-D-J regions in immune cells ('VDJome') to exploit correlations between given V-D-J sequences and antigen-specific stimulations; characterization of the microbiome used as a tracer of the environmental and physiological conditions; record of phenotypic traits and disease conditions using controlled vocabularies. Finally, George also emphasized the exponentially decreasing cost of sequencing, which will not only make large scale sequencing of full personal genomes feasible but will also potentially open entire new fields of applications based on massive DNA sequencing.
  • Lee Smolin talked about the nature of the concept of time in physics and investigated the question of whether our perception of time as the 'experience of successive present moments' is 'real' or, alternatively, an emergent property of the laws of physics. I cannot pretend I followed the entire argument, but I learned that the mathematical representation of the physical reality involves the geometrization of time (as one of the state space's dimensions), leading in fact to a representation devoid of temporal flow (somehow the clock has to be outside the system). To this geometrical representation, physical laws are associated and applied to initial conditions. If I did not misunderstand it, it appears that this approach used in physics might have to be considered as approximative because it may only be valid for subsystems of the universe whereas it might not be appropriate for a true cosmological theory of the entire universe, with possibly disturbing consequences on the nature of physical laws...
  • Believe it or not but music can be 'geekified' as well: Chris diBona, later in the evening, brought his tenori-on for a fun demonstration. I want one of those!

The meeting ended with some final scientific fireworks, when some of the speakers gave a series of brilliant 2 min summary talks, providing a colorful overview of the many sessions we inevitably had missed. I have to admit that I like fireworks and I would certainly have enjoyed having a little more of this final kaleidoscopic view of science. Clearly, the authentic value of this conference lies in the unique and direct human interactions, but I wish there would be nevertheless some way–perhaps by using this last session in some form of outreach action–to disseminate this pure joy of scientific diversity and curiosity to a broader audience.

Credits: illustrations from Bob Lee, Flickr, some rights reserved

"Free the Gene!" Fluorescent Black Graphic Novel Interview [Genome Blog]

Posted: 18 Aug 2008 03:25 AM CDT

Here’s an interesting Biopunk find! I was scanning the shelves at the local gas station and came across the September issue of Heavy Metal Magazine.  As I flipped through the pages, I came upon a graphic novel intro called Fluorescent Black by Author Matt F. Wilson. 

As fate would have it, I was honored to meet Matt through the wonders of the internet and myspace. He graciously agreed to do an interview for this Blog and the interview in full is posted in the read more link below.

Fluorescent Black is a graphic novel story of a genetic dystopian future set in Singapore and the Malaysian peninsula. Those that don't meet the norm are exiled out of Singapore and forced to survive by selling body parts in exchange for gene therapy and medicine. Human genetic experimentation and free will are inherent in the story. The question of what is human and genetic discrimination is an underlying theme as is the struggle for survival. The Art is riviting and provides contrast between pristine Singapore and the wild outside world. This is a Biopunk must have.

To fix or not to fix, that is the question [Mailund on the Internet]

Posted: 18 Aug 2008 03:23 AM CDT

Ok, I tried my fix to the BiRC webpages, but I am not sure I should have.  After the server process was restarted, all the auto-generated files were gone, and now I don’t know how to get them back.

The good news is that loading the pages will no longer crash your browser.  The gigantic files are the ones that are completely missing now.

The pages without the stylesheets look like crap, though.

How well does your genome predict your postcode? [Genetic Future]

Posted: 18 Aug 2008 03:19 AM CDT

Well, it's far from GPS precision, but the concordance between this genetic map of Europe (below left) and the physical sampling locations of populations throughout Europe (below right) is pretty good for a first draft:

The genetic map was constructed using data from over 300,000 genetic markers in 2,514 individuals from 23 European subpopulations, making it the most comprehensive analysis of European genetic variation performed to date. The map was constructed using purely genetic data without information on spatial location, so the concordance between the two maps indicates the degree to which genetic ancestry correlates with physical location - in other words, how well your genes predict your address.

Dienekes has an excellent discussion of the technical details, while Razib has labelled a plot showing all of the individuals in the study to make it easier to assess the degree of scatter and overlap.

The take-home message: rather than being one homogeneous mass, Europeans in fact show considerable population substructure, such that genetic information can be used to roughly predict geographical ancestry. An analysis of just a few hundred thousand genetic markers (i.e. less than is currently offered by personal genomics companies 23andMe or deCODEme) would be more than adequate in most cases to distinguish a Pole from a Parisian, or a Swede from a Spaniard. (To be more precise, it would be sufficient to discriminate between individuals for whom most ancestors were natives of these regions; recent migrants will obviously be misclassified.)

What drove these genetic differences? Mostly it will have been chance - random increases or decreases in the frequency of markers throughout the genome accumulated over a few millennia of genetic isolation. But at least some of these differences have been driven by natural selection: for instance, the lactase gene LCT, which has been subject to strong selection to allow lactose digestion in adults in populations reliant on dairy agriculture, represents 9 out of the top 20 most differentiated markers; a marker in the gene HERC2, which is associated with eye colour variation and has been under selection in Europeans and Asians, comes in at number 19.

This indicates that at least some of the genetic - and thus physical and possibly behavioural - differences between the various European populations stem from evolutionary adaptation to their local environments.

I'll leave the technical commentary to Dienekes, but I do want to make one important point: the accuracy of the map will have been limited by the fact that the markers used in this study represent sites of common variation; data from large-scale genome sequencing will generate far, far better maps. The major reason for this is that sequencing will provide information on rare, highly spatially-restricted variants - many of which will be limited to single families and thus be extremely informative about geographical ancestry.

Basically, if you had complete genome sequences from enough Europeans you could reconstruct the genetic map of Europe with exquisite precision. In addition to empowering genetic genealogists, researchers could use deviations between the genetic and physical maps to make powerful inferences about historical migration events and recent episodes of natural selection. With any luck, this is the sort of data that will simply fall out from large-scale population genomic studies being conducted over the next decade or so.

Update: Kambiz at puts these results in a broader scientific context.

Lao et al. (2008). Correlation between Genetic and Geographic Structure in Europe. Current Biology DOI: 10.1016/j.cub.2008.07.049

Image source: Figure 1 from Lao et al.

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Evolution as the Recycler of the Cell's Tools [adaptivecomplexity's column]

Posted: 17 Aug 2008 10:11 PM CDT

Part 2 on The Plausibility of Life

How does evolution shape living things? The fact that evolutionary forces, such as natural selection, can shape living creatures is well-established, but how malleable those creatures are, and what the increments of change are is less well established. We have a fairly good idea of how genes can change, but how does that genetic change translate into physical changes in the shape and functioning of the organism itself - that is, how does genetic change translate into changes in the organism's phenotype?

The authors of The Plausibility of Life, Marc Kirschner and John Gerhart, argue that this issue has been ignored in evolutionary theory (although they go on to say that it was justifiably ignored for a long time - before modern molecular and cell biology, there was no way to effectively address this question):

What if evolutionary biologists were wrong to think of phenotypic variation as random and unconstrained? How much would it matter if we really understood how genetic variation leads to phenotypic variation, and in particular, how facile or difficult is it to achieve a specific phenotype?

These questions get to the heart of the evolution of complexity.


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