Saturday, August 23, 2008

The DNA Network

The DNA Network

Required evolution education reading - Amy Harmon on Florida Evolution teaching [The Tree of Life]

Posted: 23 Aug 2008 07:31 PM CDT

Amy Harmon has done it again. First it was the series on the "DNA age" which had a suite of interesting pieces on the more personal side of DNA and genomics and won her one of those little pulitzer thingamajiggers. And now she has published a piece on the personal side of evolution education. This piece "A Teacher on the Front Line as Faith and Science Clash", which I think will be in tomorrow's Sunday New York Times, is really a must read for all interested in evolution education and evolution in general.

In the article, Harmon details the story of a Florida high school science teacher, David Campbell, and his efforts to teach evolution in a Biology class. I find the whole story fascinating in many ways. First, despite thinking I was paying attention, I was not really aware that Florida now required evolution to be taught in high school biology classes. Harmon details some of the history of how this came to be including how Campbell founded Florida Citizens for Science and helped push for new standards in biology teaching. Campbell's efforts to put science at the front of science teaching and to keep religious beliefs out is inspiring.

Harmon also details the trials and tribulations of Campbell actually trying to teach about evolution to high school students, many of whom come armed with anti-evolution ideas and literature. And Campbell does a great job with some subtle details --- in fact he seems to have a better grasp of evolutionary biology than many active biologists. For example, he does a good job with emphasizing that humans did not evolve from chimps but instead both evolved from a common ancestor. This is something many many biologists do not always get accurately.

I think the whole piece should be required reading for all evolutionary biologists, all biologists, and all science teachers. I confess, Harmon did ask me to glance the piece over a few days to give some feedback on a few sections, so I am perhaps a bit biased. But I am really hoping Harmon stays on this topic and does for evolution what she did for the DNA age, with a whole series on the personal side of things. This is so desperately needed with too much of the debate focusing on an argument about facts and faith and too little about the people in the trenches.

Good Open Access News from Max Planck [The Tree of Life]

Posted: 23 Aug 2008 10:12 AM CDT

Mark Patterson reports in the PLoS Blog some really good OA news (see Max Planck Society covers publication fees for PLoS journals). The Max Planck Society which has always be a strong OA supporter, will now pay the PLoS Publication fee for all papers articles where an author is affiliated with the Max Planck Institute. So now any author from there will not have to think about fees if they choose to publish in PLoS. I hope lots of other institutes follow this (not just for PLOS papers but for all OA journals).

Olfactory receptor genetics in humans and chimpanzees [Yann Klimentidis' Weblog]

Posted: 23 Aug 2008 09:04 AM CDT

Several studies of genetic signatures of selection in humans have found something going on with olfactory receptor genes, which has been difficult to interpret. Why would there be strong selection for smelling related traits in the lineage leading to humans (smelling rotting meat, tracking animals??).
In this paper, the authors look at OR (olfactory receptor) genes in humans, chimps and macaques, and finds that:
The pseudogenization rates and the numbers of genes affected by positive selection are also similar between humans and chimpanzees.
...approximately 25% of their functional gene repertoires are species specific due to massive gene losses. These findings suggest that the tempo of evolution of OR [olfactory receptor] genes is similar between humans and chimpanzees, but the OR gene repertoires are quite different between them.
Similar Numbers but Different Repertoires of Olfactory Receptor Genes in Humans and Chimpanzees
Yasuhiro Go, and Yoshihito Niimura
Molecular Biology and Evolution 2008 25(9):1897-1907
Abstract: Animals recognize their external world through the detection of tens of thousands of chemical odorants. Olfactory receptor (OR) genes encode proteins for detecting odorant molecules and form the largest multigene family in mammals. It is known that humans have fewer OR genes and a higher fraction of OR pseudogenes than mice or dogs. To investigate whether these features are human specific or common to all higher primates, we identified nearly complete sets of OR genes from the chimpanzee and macaque genomes and compared them with the human OR genes. In contrast to previous studies, here we show that the number of OR genes (810) and the fraction of pseudogenes (51%) in chimpanzees are very similar to those in humans, though macaques have considerably fewer OR genes. The pseudogenization rates and the numbers of genes affected by positive selection are also similar between humans and chimpanzees. Moreover, the most recent common ancestor between humans and chimpanzees had a larger number of functional OR genes (>500) and a lower fraction of pseudogenes (41%) than its descendents, suggesting that the OR gene repertoires are in a phase of deterioration in both lineages. Interestingly, despite the close evolutionary relationship between the 2 species, approximately 25% of their functional gene repertoires are species specific due to massive gene losses. These findings suggest that the tempo of evolution of OR genes is similar between humans and chimpanzees, but the OR gene repertoires are quite different between them. This difference might be responsible for the species-specific ability of odor perception.

rs1044396 mediates effects of nicotine self-medication via parietal cortex [biomarker-driven mental health 2.0]

Posted: 23 Aug 2008 07:24 AM CDT

thanks for sharing

It has been reported that cigarettes can impart some calm and clarity from racing thoughts and mental fog.  Patients with schizophrenia, who often experience cognitive disorganization, are 2-4 times more likely than the general population to smoke, and also seem to prefer stronger brands of cigarettes.  This is not surprising since nicotine can raise levels of dopamine indirectly via stimulation of alpha4/beta2 high affinity nicotinic acetyl choline receptors (nAChR) expressed widely in the parietal cortex of the human brain.  In an open access article entitled, “Association of attentional network function with exon 5 variations of the CHRNA4 gene“, Georg Winterer and colleagues demostrate that individuals who vary in a synonymous G/A variant (rs1044396) in the CHRNA4 gene - an snp which has previously been associated with nicotine dependence - show differential brain activity in the parietal cortex.  When asked to remain alert and respond to rare visual “oddball” stimuli (visual oddball detection task), subjects with the AA genotype showed robust brain activity in the parietal cortex while subjects with the GG genotype showed very little change in activity.  This finding reveals where in the brain - circuits connecting to the parietal cortex - may be especially important in mediating self-medication and even in the management of side-effects in psychiatric pharmacotherapy.  Although rs1044396 is not measured in my 23andMe profile, the neighboring rs3787138 showing tight LD is measured and reveals that I am a boring, middle of the road heterozygote.  As such, I do admit that I could use some mind-clearing relief from time to time - but, the yellow teeth are not quite worth it.

What happens when a mandate is exerted???? [The Gene Sherpa: Personalized Medicine and You]

Posted: 23 Aug 2008 05:40 AM CDT

Here is a quote from one of my readers... The ACOG mandate for CF testing came out while I was getting my genetic counseling degree. I gave quite a few counseling session to pregnant women regarding...

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I Spit At Coriell [Think Gene]

Posted: 23 Aug 2008 01:47 AM CDT

Yesterday, I donated my personal genome at the Coriell Institute for Medical Research to participate in the Coriell Personalized Medicine Collaborative. I also got lost in the Camden ghetto and learned to hate New Jersey. In all, it was a mixed day for magnanimity.

What is the Coriell Personalized Medicine Collaborative? (PMC)

So, what if a government institution, figuring they’ve already spent $3 billion dollars on the Human Genome Project, shrugged, and threw down a few spare million to learn how this information is actually relevant to medicine? What if this study had the institutional support of the medical establishment, the scientific establishment, and American government and thus was unlikely to try something illegal like operate a non-CLIA laboratory or suggest profit-sharing to doctors to sell tests?

And what if it was free?

Thus: the Coriell Personalized Medicine Collaborative.

The Coriell genomic test itself is like direct-to-consumer tests Navigenics, 23andMe, deCODEme… but better. Functionally, the tests use the same technology: Oragene saliva kits, Affymetrix SNP chip machines, and a web portal for reports. Both strive to test for all meaningful genomic variations that aren’t already patented, are identifiable by a single nucleotide change, and don’t risk the crushing liability and ethical problems of reporting untreatable, terminal genetic diseases like Huntington’s. But Coriell’s genomic test so much better because:

  • It’s free. Navigenics costs $2500 plus subscription, 23andMe and deCODEme both cost $1000.
    So: More people can and will participate and benefit. I believe Coriell has already recruited more participants than all other direct-to-consumer competitors combined.
    So: The resulting medical research will be better because the sample size is bigger.
  • It’s newer, so it includes more, newer, better reviewed research.
    So: Test results will be qualitatively and quantitatively better.
  • It’s medical information and is presented as such.
    So: Medical and pharmagenomic tests like “Warfarin metabolism” can be offered. (Useful if you ever need to take blood-thinning drugs.)
    So: Doctors can apply test results to practice better medicine. (How can a doctor credibly use “explicitly non-medical” information in medicine? Even if non-medical test results were available, the doctor would be obligated to repeat the test.)
  • It’s offered by a well-established medical research institution. (founded: 1953)
    So: Institutional support and funding exists.
    So: The Coriell institution can be trusted to last… unlike unprofitable, venture-funded companies less than ten years old.
    So: All people, including patients, doctors, and scientists will be more willing to invest time and money in the program.
    So: The medical establishment will be more comfortable applying the test results in medical practice.
    So: The scientific establishment will be more comfortable trusting the medical research produced by the program.
    So: Patients, medicine, and science will better benefit from their test results.

From the Coriell website:

The Coriell Personalized Medicine Collaborative is a pioneering research study that seeks to explore the utility of using genome information in clinical decision-making. The goal is to better understand the impact of genome-informed medicine and to guide its ethical, legal and responsible implementation. This research study is a forward-thinking, collaborative effort involving volunteer study participants, physicians, scientists, ethicists, genetic counselors and information technology experts. The study seeks to enroll 10,000 participants by the end of 2009, with an ultimate goal of 100,000 individuals.

With a budget of “the government,” no accountability to profit, a goal of “research,” scientific and medical institutional support, and the low, low price of free…

…screw it. I was going to say something banally optimistic like “I’m confident Coriell will continue to succeed in their endeavor to integrate genomic science into medicine.” But, really, how can Coriell fail? Not profit? They’re non-profit and funded by the government. Not get enough volunteers for their free, riskless, non-invasive saliva test worth over $2500 in sexiest, newest medical field? The government will pay to hand some nurses orgenes and waivers to distribute at a few hospitals and universities. Not able produce any successful research? Impossible: the successful research will then be “we were unable to produce any successful research.”

Basically, the only way Coriell can screw this up is if they embarrass themselves mishandling samples. This is unlikely considering they operate an international biobank of human cell lines. I met the lab director for the Coriell PMC. Where DTC companies were busted by the government for operating without certification, this guy rattled off CLIA specifications like they were trivial. Considering the hundreds-of-thousands living cell cultures preserved in liquid-nitrogen-cooled vats downstairs, to him, for a few SNP chip machines and some dead somatic cells in spit, they were.

The good news for genomic testing DTC competitors 23andMe, Navigenics, and deCODEme is that they were the trailblazers and that Coriell is following their lead. The bad news is that another word for “trailblazer” is “cannonfodder.” Sure, you might get a statue, but you’re dead. (It’s typically bad for business when an established, well-funded, experienced competitor releases a better version of your product for free.) So what will these statues look like?

  • 23andMe: 23andMe is the biggest winner because it has already accomplished everything it was founded to do: launch the biologist wife of a nerdy silicon valley billionaire into high society while ostensibly achieving something important. Technically, deCODEme launched before 23andMe, and technically, a .5MM SNP chip isn’t a genome, but 23andMe, particularly, Anne Wojcicki, will be remembered for being the first to realize the $1000 genome. (If this is confusing, what’s called “philanthropist” is called “web 2.0 startup founder” in Mountain View, CA.)
  • deCODEme: deCODE clearly expected to profit from deCODEme eventually, but how does one expect to compete in a market with immortal competitors like Coriell? deCODE will continue to sell its genomic tests, but deCODEme has been notably quiet lately and will likely continue to get quieter… Fortunately, deCODE didn’t invest much into deCODEme since they already have a lab and websites are comparably cheap.
  • Navigenics: To Navigenics, the “serious medical brand” of DTC genomics, Coriell’s PMC isn’t so much “bad news” as it is a big “F-You” shouted self-consciously at effigy of Craig Venture in a Navigenics t-shirt.  It wasn’t enough demolish Navigenics’ business model; Coriell had to completely discredit any hope of Navigenics ever being considered as a credible medical tool by any medical establishment. Fortunately, “Navigenics does not provide medical advice, diagnosis or treatment,” so that’s not a problem for Navigenics… right?

While I know that Coriell will be successful, the degree of that success is uncertain. Coriell is a non-profit science company trying to reach the mass public, so its greatest weakness will be marketing. For example, a Google search reveals 471 hits for “Coriell Personalized Medicine Collaborative” versus 365,000 for 23andMe.

Coriell will also need some help with their web software portal. (for example: is temporarily offline). But as a smart 15 year old can run a basic web server, Silicon Valley has already built several good genomic web UIs for “inspiration” (hint: Print Screen + View Page Source + Django | Ruby on Rails == ++Inspiration), this is an feasibly addressable issue.

So what does the Coriell PMC mean for the future of genomic medicine?

First, the market for expensive SNP chip tests for unpatented mutations is dead. Genomic testing companies will still exist, but they’ll be more like products offered by commodity medical test providers than sexy consumer brands. I must repeat: any customer of DTC genomic testing can get a better test for free from Coriell. There is no reason for anyone to ever again buy any DTC genomic test other than to conspicuously spend money (up to 100,000 participants, but that is enough to kill today’s $1000 SNP test market.)

A market for expensive patented genomic tests like BRCA will continue to exist because it’s illegal for organizations like Coriell to provide them for free (even though they could easily do so). However, the good news for consumers is that these patents will become increasingly unenforceable as full-genome sequencing replaces SNP chip technology. At first, testing companies will refuse to provide official interpretations of legally conflicted results, leaving them as “exercises for the reader.” But as patents are public and “trade secret” medical science is quackery, eventually, BRCA-type patents will seem ridiculous and fade away. Maybe not in five years, but certainly in a few decades.

Ultimately, if the government is willing to pay to bring SNP chip genome testing to the masses, then it will be willing to pay to bring genome sequencing testing to the masses when it’s cheap enough. It will be. Eventually, a genome sequence will be performed with as much institutional banality as childhood vaccines. Your genome will go into some medical record where it will be used to aid every medical decision. This will normal and unnoticed except the occasional slow news day when MSN Health reports some prole alarmist dreck like “Is Your Genome Really Private?” or “Top Ten Mutations That Affect Your Health.”

Every variable: cost, medical application, availability, liability, institutional capacity… inexorably points to this the “genome banality scenario” except one: some pseudo-religious aversion to sharing one’s genome. However, the pressures to solve mounting health care costs, provide better care, and to avoid liability will be too great. GINA may protect Americans from discrimination based on what one’s genome says, but it does NOT protect discrimination based on not having a one’s genome on record.

Remember, you read it here first!

So with the DTC genomics SNP chip market dead, how does one make money in the new genomics industry? That will be the topic of my upcoming series: “How to Make A Bazallion Dollars in Genomics.”

Another image search engine [business|bytes|genes|molecules]

Posted: 22 Aug 2008 11:01 PM CDT

I’ve covered image mining in scientific literature in the past (here and here). Bioinform points us to another image search engine. The Yale Image Finder is a search engine that uses the text inside figures in addition to other features such as captions, etc

Check it out and the others. I don’t have a sense for how successful the engine is for various kinds of images. I had more success using “captions” for molecular dynamics. The results for “image text” were not satisfactory.

It is good to see a few things; decent performance (at least at this time), decent site design, and an effort in the community to try and develop tools of relevance. In an image heavy field like the life sciences, relevant image search is going to be important, so such efforts are to be lauded.

Read the abstract. It is amusing that the paper was published in a closed access journal, since the Yale Image Finder searches “the actual image content of over 34,000 Open Access articles from PubMed Central.”

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Any leads on when pandas join the genome club? [Omics! Omics!]

Posted: 22 Aug 2008 10:01 PM CDT

Tonight's bedtime conversation veered all over the map (par for the course), but at one point touched on the announced Chinese effort to sequence the genome of the giant panda. Of course, a key concern was that this did not involve any pain or injury to the beloved bicolors, so the concept of buccal swabbing was introduced.

This project was announced last spring. I thought it was planned to be released during the Beijing Olympics, but that is apparently an invention of my imagination.

So, anyone out there in the know care to hint or leak? When will the first ursid genome arrive? And who was the lucky bear?

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