Wednesday, August 27, 2008

The DNA Network

The DNA Network

Common Responses to Why DTC Genomics is Dead: Coriell PMC [Think Gene]

Posted: 27 Aug 2008 08:54 PM CDT

First, thanks for the great comments about my Coriell PMC post yesterday.

“To use the Coriell service you have to actually walk in the door. If you’re not in the neighbourhood then it may be easier and cheaper to use 23andMe.”

Right, but that’s because Coriell have no incentive to rush to seize a market. Coriell could mail their saliva oragene collection kits and probably, eventually will. Remember, Coriell is an international biobank. It’s their business to send and receive biological samples by mail.They don’t because requiring participants to physically visit their office carefully limits the scale of their program. Coriell will probably be forced to send kits by mail to achieve their goal of 100,000 participants.

Further, for the $2500 cost of a Navigenics test, a better, free, declaratively medical test from Coriell is worth the daytrip and flight for the majority of people. The same is true for a $1000 23andMe or deCODEme test. Come on, this isn’t some fire sale at some outlet store in Kansas, this is an expensive medical test.

“Coriell will not give you access to your raw data, only their interpretation of items that they consider ‘medically actionable.’”

So? I don’t get back the raw data of any other medical tests I take. If you just want a SNP sample of your genome because it’s cool, go buy a 23andMe or deCODEme test. That’s like getting an x-ray because you “want to see what your bones look like.” OK, some people may want to do this… and hey, I bought a 23andMe test for this reason… but most people aren’t choosing their x-ray test provider based on whether they get to keep their x-rays.

“The author is naive if he thinks that this initiative is going to wipe out all the for-profit ventures in this arena.”

No, of course DTC genomic companies aren’t going to be immediately wiped out. People will continue to buy DTC genomic tests, and most of the fly-by-night competitors have already been swept away by regulatory scares.

The problem is that DTC genomic companies aren’t profitable. They are investment-funded companies. (deCODE is a public company, but it too has never been profitable and operates by spending investment.) To raise additional capital to continue operation, these companies must convince investors that they will earn a return on their investment. However, given the Coriell PMC, investors must be convinced despite that

  • The current market price of a genomic test has dropped from $1000 to $0 for the first 100,000 customers.
  • The government has proved that will fund competing efforts to offer the same services and perform the same research. These efforts will use superior, better established institutional resources and have no obligation to return capital.
  • (BIGGEST) The existing medical research establishment has proved that it will conduct its own genomic services and research rather than work with venture-funded startups like Navigenics.

Especially for Navigenics, the idea is that these tests will eventually be medical information to be used by doctors and purchased by pharama companies. That is the investment. Unfortunately, the Coriell PMC is a political statement that clearly states: “No, we don’t want or need your company. We will provide these ourselves, we will undermine the market for your genomic data by conducting the same research better than you can, and we’re not going to help you.” This is FAR worse than the former two points because it extends to hypothetical genomic products like sequencing, not just SNP set tests. Otherwise, one could make a credible argument that the Coriell PMC will prime the genomic testing market with government money, and once the project concludes, a company like Navigenics would be ideally suited to serve that market (assuming it was well-enough funded to weather the government-sponsored “free trial.”)

“Actually, GINA says that insurers/employers cannot request or require that you take a genetic test. So discrimination based on *not* having a test is still illegal.”

This merits its own post (coming)…


Evolution's Most Important Molecular Inventions [adaptivecomplexity's column]

Posted: 27 Aug 2008 05:16 PM CDT

Most people probably think of change when they hear the word evolution, but some of evolution's most amazing molecular inventions have stuck around hundreds of millions, even billions of years. The complex protein machinery needed to express genes, metabolize energy sources, reproduce sexually, and lay out body plans has remained in place largely unchanged in spite of the tremendous variety we see in the living world. These constant core cellular processes are why biologists could crack the universal genetic code by experimenting with bacteria, and why we gain insight into cell division and cancer by studying yeast.

The big question, argue the authors of The Plausibility of Life, is not how evolution keeps inventing new genes - it's how evolution can produce so much variety when the basic processes change so little. Later in the book Kirschner and Gerhart are going to argue that these basic systems have persisted so long because they are versatile, that they posses features which make them well-suited to facilitating the biological diversity we see today. We'll come to that argument later; today we'll take a closer look at the core conserved molecular systems that carry out the most basic cellular functions.


Let's talk about facts this election - Part I - Taxes [The Daily Transcript]

Posted: 27 Aug 2008 04:37 PM CDT

Fact #1: There's a clear difference between Obama and McCain on taxes.


(ht: Digby, Crooks and Liars, Washington Post)

Read the comments on this post...

Mumps outbreak in Vancouver [Discovering Biology in a Digital World]

Posted: 27 Aug 2008 03:00 PM CDT

It's déjà vu all over again.

The first chapter in Arthur Allen's book "Vaccine" describes the history of smallpox vaccination in the United States. In 1721, in Boston, the prevailing belief was that to get vaccinated was to intervene with "divine providence." If you tried to protect yourself, it meant that you lacked faith in God.

Today, I read that a mumps outbreak is happening in Vancouver, Canada. So far 116 cases have been confirmed.

Why is mumps, a preventable and serious disease, causing problems in Canada?

photo of a child with mumps by by Barbara Rice, from the Public Health Image Library

Read the rest of this post... | Read the comments on this post...

Misrepresenting the Church [Mary Meets Dolly]

Posted: 27 Aug 2008 02:20 PM CDT

I really hate it when Catholics deny the teachings of their own church and then say that they are still staunchly Catholic. So you don't agree with Church teaching on abortion, embryonic stem cell research, euthanasia etc? Fine. Just say you disagree. Don't say that you support abortion on demand and then pretend that you follow Church teaching to the letter.

It irks me because it makes non-Catholics confused. My neighbors just recently moved. It wasn't until the last weeks before they left did they discover that I was staunchly pro-life. They knew I was Catholic from the moment they moved in, but they were afraid to express their pro-life views because most Catholics they encountered previously thought Roe vs. Wade was the best thing since sliced bread. Unfortunately, their experience with "cafeteria catholics" had left a bad taste in their mouth and had them seriously confused about the Church's teaching on the sanctity of life.

I hate it more when this phemenon occurs at the national level as in the case of Nancy Pelosi who swears up and down she is a faithful Catholic but at the same time thinks abortion is morally acceptable.

Let us clear the air and dispell any confusion. The Catholic Church teaches that because science shows that a new human life begins at conception, and we can never know for certain when we are ensouled by God, we must err on the side of life and protect all human life from beginning to end. There is no "magic" cell division where we suddenly become human enough to deserve dignity and protection. This means that embryo-destructive research, abortion at any stage and assisted suicide are morally WRONG!

This is not a debatable Church teaching. But do not take my word for it. Here is an official Church statement responding to Nancy Pelosi's blatant disregard for Catholic moral teaching:

Cardinal Justin F. Rigali, chairman of the U.S. Bishops' Committee on Pro-Life Activities, and Bishop William E. Lori, chairman of the U.S. Bishops' Committee on Doctrine, have issued the following statement:

In the course of a "Meet the Press" interview on abortion and other public issues on August 24, House Speaker Nancy Pelosi misrepresented the history and nature of the authentic teaching of the Catholic Church against abortion....

In the Middle Ages, uninformed and inadequate theories about embryology led some theologians to speculate that specifically human life capable of receiving an immortal soul may not exist until a few weeks into pregnancy. While in canon law these theories led to a distinction in penalties between very early and later abortions, the Church's moral teaching never justified or permitted abortion at any stage of development.

These mistaken biological theories became obsolete over 150 years ago when scientists discovered that a new human individual comes into being from the union of sperm and egg at fertilization. In keeping with this modern understanding, the Church teaches that from the time of conception (fertilization), each member of the human species must be given the full respect due to a human person, beginning with respect for the fundamental right to life.

Dr. Anonymous Show: One Year! [ScienceRoll]

Posted: 27 Aug 2008 02:15 PM CDT

I’m a fan of people who are inspired enough to create something really unique on the web. Doctor Anonymous launched his radio show a year ago and he keeps on featuring medical bloggers, physicians, nurses and medical students.

Join us Thursday, August 28, 2008 at 9pm eastern time for Show 46 of The Doctor Anonymous Show. We will be celebrating our one year anniversary (yes, I haven’t been cancelled, yet). Join us in the chat room, see me on the web cam, call into the show to say hello. And, we will also be having Ask Doctor Anonymous. What’s that? Well, tune in to find out!

This March, I was featured in one of his shows and woke up at 2:30 AM to talk with him for an hour. It was a fascinating experience.

The preview of the show.


Genomic Medicine on CD [ScienceRoll]

Posted: 27 Aug 2008 02:02 PM CDT

Helix Gene, The Foundation for Genomic Health Education just released two Clinicasts on CDs to let us listen to valuable discussions about genomic medicine while sitting in a traffic jam. An excerpt from the mission statement:

The foundation’s mission is to educate all healthcare participants about the promise of genomic medicine and enable its delivery to the patient.

You can order those here.

Intelligent Molecular Design [Sciencebase Science Blog]

Posted: 27 Aug 2008 01:00 PM CDT

Alchemist LogoFirst up in The Alchemist this week is a tale of reactions where size really does matter! News of why “non-smokers cough” emerges from the American Chemical Society meeting this month and a new physical process has been revealed by NMR spectroscopy of frozen xenon atoms that could provide a chaotic link in quantum mechanics back to Newton’s era. Biotech news hints at a novel way to flavour your food and Japanese chemists have made a gel that undulates like intestinal muscle. Finally, this week’s award goes to my good friend AP de Silva of Queen’s University Belfast for his highly intelligent work in the development of market-leading sensor technology and intelligent molecules.

You can grab the complete headlines and abstracts in the latest issue of The Alchemist on ChemWeb (just in case that link is not live right when this post posts, The Alchemist homepage is here.


Intelligent Molecular Design

Warfarin DNA Testing Reimbursement Public Comment DEADLINE Wednesday 9/3/08 [A Forum for Improving Drug Safety]

Posted: 27 Aug 2008 11:33 AM CDT

Here is a recent email sent by Genelex’s CEO, Howard Coleman to people with an interest in personalized medicine:   

It’s time to express your opinion on whether warfarin (Coumadin) DNA testing should be paid for by insurance. The Center for Medicare and Medicaid Services (CMS) has initiated a study of this topic and is accepting public comment until September 3, 2008 at

In the interests of the approximately 500,000 patients who begin warfarin therapy every year, I’m in agreement with Larry Lesko of the FDA that warfarin DNA testing should be widely adopted. This linked article by him clearly summarizes evidence in favor of warfarin testing that has built up over the years. The contrary position outlined at focuses on the lack of evidence from prospective clinical trials without citing contrary evidence. This standard of proof is unreasonable in this application and I believe that adherence to unreasonably difficult standards of proof for pharmacogenetic tests has resulted in harm to many, many patients.

It’s important that you comment on this study because the decision made by CMS will have a wide impact on patient access to these tests that represent one of the greatest opportunities for Personalized Medicine to improve healthcare. A recent story in the Pharmacogenomics Reporter has many of the details
I have since posted a public comment myself, here is the text:

The American College of Medical Genetics review of a decade or more of warfarin dose variability research, estimates that 23% of the variance is due to polymorphism in the VKORC1 gene and 17% in the CYP2C9 gene, compared to 9% for weight and 7% for age. These estimates are not in dispute and there is virtually no evidence contradicting them.

Physicians would not prescribe without age, weight and other clinical information, yet continue do so without genetic test results. Waiting for more trials to further prove that the use of genetic testing will improve health outcomes is dangerous to patient safety.

Would you drive with 16% visibility when you could have 56%? Let’s draw a comparison; say that 23% of traffic fatalities involve alcohol, 17% involve drugs, 9% involve poor driving conditions and 7% involve drivers with less than two years of driving experience. We cannot eliminate young drivers or poor driving conditions, but it is safe to assume that reducing the number of drivers drinking or on drugs would reduce the number of traffic fatalities. If this were held to the same difficult standards some propose for warfarin DNA testing, we would need a blinded study proving that reducing the number of drivers on alcohol and drugs would decrease the chance of automobile fatalities before action could be taken. How many lives would be lost in the interim?

“First do no harm” is not being followed if we ignore 40% of the causes of dose variability in a drug with a narrow therapeutic index in which misdosing causes a high incidence of adverse thromboses and dangerous bleeding events. As John Concato, MD, Director, VA Clinical Epidemiology Research Center at Yale University says “Putting what we know into practice would prevent more disease than worshiping at the altar of randomized trials.”

Please take the time to let your voice be heard on this important matter.



Cultured melanocytes, genotypes and gene expression of skin color genes [Yann Klimentidis' Weblog]

Posted: 27 Aug 2008 10:29 AM CDT

Analysis of Cultured Human Melanocytes Based on Polymorphisms within the SLC45A2/MATP, SLC24A5/NCKX5, and OCA2/P Loci
Anthony L Cook, Wei Chen, Amy E Thurber, Darren J Smit, Aaron G Smith, Timothy G Bladen, Darren L Brown, David L Duffy, Lorenza Pastorino, Giovanna Bianchi-Scarra, J Helen Leonard, Jennifer L Stow and Richard A Sturm
Journal of Investigative Dermatology advance online publication 24 July 2008;
Abstract: Single nucleotide polymorphisms (SNPs) within the SLC45A2/MATP, SLC24A5/NCKX5, and OCA2/P genes have been associated with natural variation of pigmentation traits in human populations. Here, we describe the characterization of human primary melanocytic cells genotyped for polymorphisms within the MATP, NCKX5, or OCA2 loci. On the basis of genotype, these cultured cells reflect the phenotypes observed by others in terms of both melanin content and tyrosinase (TYR) activity when comparing skin designated as either "White" or "Black". We found a statistically significant association of MATP-374L (darker skin) with higher TYR protein abundance that was not observed for any NCKX5-111 or OCA2 rs12913832 allele. MATP-374L/L homozygous strains displayed significantly lower MATP transcript levels compared to MATP-374F/F homozygous cells, but this did not reach statistical significance based on NCKX5 or OCA2 genotype. Similarly, we observed significantly increased levels of OCA2 mRNA in rs12913832-T (brown eye) homozygotes compared to rs12913832-C (blue eye) homozygous strains, which was not observed for MATP or NCKX5 gene transcripts. In genotype–phenotype associations performed on a collection of 226 southern European individuals using these same SNPs, we were able to show strong correlations in MATP-L374F, OCA2, and melanocortin-1 receptor with skin, eye, and hair color variation, respectively.

Redefining Tomorrow's Table [The Tree of Life]

Posted: 27 Aug 2008 10:19 AM CDT

Tony Trewavas has an interesting review (Redefining "Natural" in Agriculture) in PLoS Biology of my friend and colleague Pam Ronald's new book "Tomorrow's Table: Organic Farming, Genetics and the Future of Food."

I was planning on eventually writing my own review of her book but not sure when I will get to it. I personally like the book a great deal, and enjoy how it switches back and forth between the authors (Pam and her husband Raoul Adamchak) and how it interweaves personal stories with discussion of the science and practice of organic farming and plant genetic engineering.

Trewaras has some things in the review I agree with a great deal like
"The text deals with many of the questions raised by the public about GE crops in a sensible and balanced manner, quoting various sources of reliable information on the concerns about risks to health and environment that often recur. It also mentions Richard Jefferson, who is Chairman of CAMBIA, a non-profit organisation that attempts to make the tools of biotechnology widely and freely available ( As a scientist, I cannot help but applaud!"
I personally love what CAMBIA is doing and found the discussion of CAMBIA in the book to be interesting. I have gotten to know Richard Jefferson over the last few years and think he is a true pioneer in revolutionizing biotechnology and freeing it from the shackles of over protectionism.

Trewavas also has a very interesting thread about the value of different opinions. Since this was printed in PLoS Biology and is under a CC license I can reprint it here (with acknowledgment of the source - Citation: Trewavas T (2008) Redefining "Natural" in Agriculture. PLoS Biol 6(8): e199 doi:10.1371/journal.pbio.0060199) and it is worth doing so:
The continuing conversation did not resolve the issues between them. It convinced me, however (if I needed convincing), that while everyone is entitled to their opinions, when dealing with detailed technical matters of science or medicine or any subject that requires enormous qualifications and experience, the notion that all opinions have equal validity is simply downright wrong. If you want real information on the safety of heart surgery procedures, do you follow the advice of a qualified heart surgeon or the local butcher? If you want advice on flying a jumbo jet, do you ask the local bus driver or a pilot with 10,000 hours of experience flying jumbo jets? And if you want advice on how to captain a supertanker, do you ask a person whose experience is limited to rowing a dinghy? Mistakes by surgeons are not uncommon, 70% of air crashes result from pilot error, and occasionally supertankers hit the rocks. But relying on rank amateurs instead of professionals would guarantee instant catastrophe. Many branches of science are very complex. However, being a scientist isn't enough, of course, as being a scientist doesn't qualify you to advise on any subject except your specialty. To provide advice that can lead to sensible policy requires not only a thorough understanding of the workings and literature of the particular scientific area but many decades of experience in that field.

It is unfortunate that for the past 40 years, agriculture in particular has been damaged by opinionated groups of the public that have forcefully used fear and anxiety and carefully selected information to try and coerce policy makers to adopt their own mistaken and unqualified views. Fear and emotion do not make for good policy. I applaud Ronald's conclusion that "if citizens vote, it should be for a specific matter on which they are well informed, not because of general concerns about a new technology."

The corollary is that on most technical matters, the public can never be well enough informed. If scientific knowledge does not form the basis of policy on technology, basing such policy on ignorance can be guaranteed to generate disaster. It was Slovik in his classic Perception of Risk [3] who demonstrated that non-experts overestimate the frequency of death from rare causes while underestimating the frequency of common causes of death, and who established clearly how additional knowledge changed expert understanding. The use of the local ordinance by activist groups to stop GE farming is only too reminiscent of the damage done by Lysenkoism to Soviet farming in the 40s, which took decades to recover from, once it was abandoned.

Basically, he is indirectly agreeing with Ronald/Adamchak that some negative opinions of GE are simply not valid. Here I think I disagree with all of them. I think much of the objection to GE modification of plants is an esthetic objection and thus presenting scientific arguments for why it is OK to do is a bit off tangent. It is kind of like when someone says "that house is ugly." Do you respond by saying "Well, actually, the shape and color patterns have been shown to appeal to human sensory systems" Not too helpful. I feel that the same is happening with GE plants --- if people's instinctively do not like them, telling them about the science is not necessarily going to help. Nothing wrong with educating about the science, but I think it is a red herring to say that some of the anti-GE folks do not understand the science and therefore their objections must be wrong. I feel similar vibes in the evolution education discussion going on around the world. I think many people latch on to ID and Creationism because it appeals to them in a esthetic sense. And one needs to be really gentle/careful about bringing science into the discussion (except of course, when one is teaching a science class --- then you teach the science).

So sure - I have some quibbles about parts of the book. As does Trewavas (he has to raise some objections - any book review that does not have them seems like fan mail and not a review).

Despite my quibbles here and there, the book really is a must read for those interested in GMOs and/or the organic farming movement as well those thinking about "slow food" and other related topics. In addition it is a wonderful personlized story, with a mixture of recipes, stories of research, discussions of teaching about organic agriculture, and some minor family drama. For the same reason that I like Amy Harmon's New York Times stories (such as the recent one on evolution) I like this book - it personalizes what is frequently a boring impersonal discussion.

And of course it does not hurt that the heart of the story / discussion is good. Ronald/Adamchak present an overall idea I have a hard time arguing against - GE and organic growth practices both have a lot to offer the world and if we took the good parts of both, a "GE-Organic" system might be highly beneficial to all. For example, in principle, GE plants can lead to a reduction in the use of pesticides and fertilizer. Similarly, they could lead to a reduction in water use and higher crop yields. Since it seems unlikely that the current organic movement will embrace the benefits of GE crops, it will probably require a whole new movement to merge the two. It will also require the companies and organizations that push GE to do it with the environment and health of people and the planet in mind. To me, the biggest problem with GE food and farming is that it seems to be used more to help the farmers and the companies selling stuff than the consumers and the public. If that changed, I can see people embracing GE plants in much the same way they embrace GE medicines.

PS - For more on the book see Pam's blog here.

Put Thinking on Your To-Do List [adaptivecomplexity's column]

Posted: 27 Aug 2008 10:03 AM CDT

This piece is a little old, and is ostensibly about Presidential candidates, but the advice applies to anyone with a 'wired' job who needs to think, including scientists and science writers:

In London, Obama and [British Conservative Leader] Cameron commiserated about their days, which are arranged in 15-minute intervals of crisis. They react, but they never have time to reflect. Cameron said he tried to not let aides "chalk up" his schedule with too many commitments. Obama's solution was to set aside time to let his brain work during his mid-August vacation. "The most important thing you need to do is to have big chunks of time during the day when all you're doing is thinking," he said...

The problem is becoming especially acute in science.


Peering into PLoS One comment stats [business|bytes|genes|molecules]

Posted: 27 Aug 2008 09:00 AM CDT

PLoS ONEImage via Wikipedia I was one of the lucky few who was given access to a dump of “social” statistics for PLoS One (my term). The data were given to us to analyze as we please, to glean from them what we may (I don’t really know who all the others were).

To give some context, we need to look back at Euan’s post on commenting. He does a great job of slicing and dicing the data from BMC. My first instinct was to do a similar analysis of data from PLoS One, but in the end decided to go in a slightly different direction and look at some trends that might give some semi-quantitative insights into the scientific mind and commenting, and provide some commentary on what this really means, if anything.

In the time since the first comments on PLoS One, in December 2006 (I show up as an early commenter, which felt kinda nice), over 710 people have commented with an average of ~2 comments a person (about half have left more than one). Given the diversity in the kinds of papers people publish that number is higher than I expected. However, it could (should?) be a lot better. Not surprisingly, as the following figure shows, there is a very spiky distribution among those who do comment, with a few commenters, including Björn Brembs, commenting a lot more than others.

What’s a little more interesting is the number of people that have not left a single comment. I would love to know what the ratio of people who engage with a paper (spend a certain amount of time on it) to the people who end up commenting is. My guess is that the percentage of people who do leave a comment is somewhat small, given that the total number of people visiting PLoS One is probably significantly higher than 710. As a blogger, interacting with others through a comment stream (either on the blog or on sites like Friendfeed) is one of the more rewarding aspects. The stats tell us that we are a long way away from publishing platforms essentially becoming micro-communities. Let’s say you have a particular lab, e.g. a group publishing papers on the photophysics of bacteriorhodopsin. If the group published 2-3 papers a year at PLoS One, each paper could become a discussion board, with authors and others in the field having a discussion. In a perfect world, all these people would comment on each others papers and via cross-linking, etc you’d get a vibrant bacteriorhodopsin community. This is essentially an extension of the now infamous data finds data, people get people meme that the whole world should latch on to.

Alright, enough flights of fancy, lets look at some more numbers. The one thing I could not find was any correlation between ratings and commenting, which did surprise me a little bit. As you can see going from left to right (which essentially is a function of time) there seems to be a burst of activity right in the beginning, but other than that you get a nice little skyline with a fairly steady output. Depending on your point of view, that’s a good thing or a bad thing. If you want to be a naysayer, you can say that things have not progressed as they should, with increasing reader engagement. On the positive side you could note that there has been no drop off, and people continue to remain engaged and every now and then you get a paper which yields more interest than others. If you presume that the 2008 numbers will hold for the rest of the years, you essentially get some growth, but not by much, but at least there is no drop off.

When PLoS launched trackbacks I remember being quite excited, but if there was one area that disappointed me, it was the lack of trackbacks. The numbers are loud and clear here. If you take out trackbacks from Bora and other PLoS staff, the number is less than a 100 for all PLoS One papers and a maximum of 4 for any paper. This is a combination of flaws in the trackback system in general (could write a whole blog post on that) and perhaps with the PLoS implementation. The folks at PLoS really need to think about how they could leverage trackbacks, and perhaps could take the lead in integrating trackbacks with DOIs, to try and resolve various links that point to papers published on PLoS One

Earlier I had talked about microcommunities. There I had compared a paper to a blog post (hold your horses, it was just an analogy). A different analogy would be the Life Scientists room at Friendfeed or a site like Hacker News. There people post a link and a whole discussion erupts (not always, but often enough). I would throw out this challenge (see the DOI suggestion above). Why should discussion be localized to PLoS One itself. If a paper pubished in PLos One is discussed in 20 other places, it would be considered a success. In other words, we shouldn’t limit our thinking to just on site commenting. Perhaps within the site, we should be focussed on ratings and perhaps tagging and notes.

I’d like to end this post with another figure. The quantity of comments might not be quite what some of us had hoped for, but it would seem that the recent trend is somewhat encouraging as seen in the following figure (ignoring that last data point).

So what have we learned from this exercise. Quite frankly, I am not sure. Is the commenting on PLoS One at a level that we hoped it would be? Not quite. Is it as bad as some might like to believe? Not quite. What we have is a very very nascent (no pun intended) effort on the part of the scientific community using web publishing platforms as a communication medium. I’d like to ask those same scientists to think about newsgroups. Most scientists are fairly comfortable participating in newsgroups, and here you essentially have one, with very clearly defined thread titles.

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Political Check In: Kucinich and Clinton Hit Homeruns [The Daily Transcript]

Posted: 27 Aug 2008 08:30 AM CDT

Last night we spent the night at the Cambridge Brewing company and said goodbye to Marius Wernig who is leaving today to start his lab at Stanford. If you are looking for a lab working on a hot topic and want a patient smart and generous mentor APPLY TO HIS LAB. Trust me. (To read more, click here.)

When we got home we watched Clinton's speech at the MSNBC site. It was great. If you missed it, I'll present it to you via the magic of the intertubes:

Read the rest of this post... | Read the comments on this post...

Using DNA to Examine James Madison’s Family Tree [The Genetic Genealogist]

Posted: 27 Aug 2008 07:46 AM CDT

imageAccording to a 200-year-old family legend, Bettye Kearse - an African American - is the direct descendant of James Madison.  Madison, of course, was a founding father and fourth President of the United States.  As the story goes, he fathered a child name Jim with a slave cook named Coreen.  For the past 4 years she and genetic genealogist Bruce Jackson of the Roots Project have tried to use DNA to prove or disprove a story passed through 5 generations of the family.

Unfortunately, Kearse and Jackson have been unable to obtain DNA samples from Madison’s descendants, stating that they have been “neither sincere nor forthcoming in this effort.”  The president of the National Society of Madison Family Descendants, Frederick M. Smith, cited confidentiality concerns and declined to comment.

An article in the Washington Post describes the situation.  According to Smith, “his society has received several claims of family ties to the president over the years and those wishing to test their DNA against that of a Madison family descendant can do so through an online genetic testing service, a method he called objective and without racial bias.”  However, Jackson called the approach “scientifically flawed.”  I disagree with Jackson; this method would clearly shed light on the question.  Of course a negative result will mean more research and testing, but a positive result would really get the ball rolling.  I also don’t believe that Jackson’s lab or organization should perform the comparison; it clearly should be a neutral third party.

The Madison Society has suggested that Family Tree DNA be used to compare Kearse’s DNA to DNA from an anonymous Madison descendant.  According to the article, Jackson maintains that “there was no way to verify, genetically or historically, whether the so-called Madison DNA being used for the test would be valid. If the test came back negative, he said, it would prove nothing, but Kearse’s claim might still be dismissed as false.”

Of course, traveling down the Madison family tree is not the only direction to go.  I’m sure Kearse will be able to identify a distant Madison relative who will be willing to submit a DNA sample.  Indeed, in December, “Jackson traveled to England to meet with a British genealogist in hopes of locating a descendant of Madison’s great-great-grandfather, John Maddison Sr., a ship’s carpenter who emigrated to Virginia in the 1650s.”

Epigenetic keys to brain repair [biomarker-driven mental health 2.0]

Posted: 27 Aug 2008 06:21 AM CDT

Siming Shen et al., in their paper, Age-dependent epigenetic control of differentiation inhibitors is critical for remyelination efficiency provide insight on basic mechanisms of myelination.  While myelination (think of it as the plastic insulation on copper electrical wires) makes normally developing neural networks much more efficient, it has a way of inhibiting the re-development and repair of mature neural circuits. The research team shows that recruitment of histone deacetylases (HDACs) is rather inefficient in mature oligodendrocytes precursor cells (the cells that adhere to bare neuronal axons and form the insulating myelin-rich sheath) in contrast to younger cells which differentiate readily.  HDAC1 and HDAC2 are shown to down-regulate of Hes5 and Sox2, which have previously been implicated in blocking the differentiation of stem cells to oligodendrocytes.  Here, the term ‘epigenetic’ refers to the mechanism of gene regulation - not by way of transcription factors binding to specific sequences - but rather, by factors being sterically blocked from binding by the 3-dimensional superstructure of the chromosome that occurs when histone proteins are deacetylated.  The team suggests that as the brain ages, it becomes more difficult to recruit HDAC1,2 to the promoters needed to shut down the expression of the differentiation inhibitors.  The results pose a confound for the certain applications of inhibitors of histone deacetylases (HDACi) which have demonstrated anti-tumor activity - but may - as suggested by this article - have negative consequences on brain repair processes.

Diagrammatic notation of celluler processes standardized [Reportergene]

Posted: 27 Aug 2008 02:42 AM CDT

Via I have been acquainted with the first specification for Process Diagrams of the Systems Biology Graphical Notation (SBGN) announced yesterday. The goal of SBGN is to standardise the graphical representation of essential biochemical and cellular processes. Standardising graphical notations for describing biological interactions is an important step towards the efficient communication of biological knowledge between different communities. More information on SBGN and SBGN Process Diagram Level 1 can be found here

In september, after the august truce, there is a burst in standardization (according to google trends)

Maq in the Literature [FinchTalk]

Posted: 26 Aug 2008 11:13 PM CDT

Kudos to Heng Li and team at the Sanger Center. Today Genome Research published their paper on Maq.