Friday, October 10, 2008

The DNA Network

The DNA Network

October and November is Personalized Medicine 2 Months! [The Gene Sherpa: Personalized Medicine and You]

Posted: 10 Oct 2008 04:14 PM CDT

That's right. Personalized medicine is such a hot topic that we deserve 2 months! Why Not? I will get W. on the phone and make it so! Seriously though, there are some excellent conferences on the...

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Green Fluorescent Protein is Cool, but is it Nobel Prize-Level Cool? [adaptivecomplexity's column]

Posted: 10 Oct 2008 03:08 PM CDT

This year's Nobel Prize in Chemistry goes to three scientists responsible for transforming a green-glowing jellyfish protein into a ubiquitous tool in molecular biology. Green fluorescent protein (or GFP in lab jargon) and its various colored relatives have made many previously impossible experiments cheap and easy, and you would be hard-pressed to find any molecular or cell biologists who have never used some variant of GFP. There is no denying the influence of GFP, but was its discovery Nobel-caliber?


San Diego Beach Scene, Fluorescent E. coli on agar, Nathan Shaner, photography by Paul Steinbach, created in the lab of Nobel Prize winner Roger Tsien, posted under the GNU Free Documentation License

Read More...

Harper government want to dismantle federal laboratories [Bayblab]

Posted: 10 Oct 2008 02:43 PM CDT

I found this story in this really informative Canadian science policy blog. Apparently the treasury board was commissioned to report on the feasibility and the roadmap to dismantle government labs such as Agriculture Canada and the Geoscience laboratory here in Ottawa to either privatize it or transfer it to academia:

"From August to December 2007, the panel scoured the world for models of government S&T commercialization via "major programs of privatization of both regulatory and non-regulatory laboratories and/or through creation of new government agencies that have special authority to pursue private-sector-like activities." The range of initial transfer arrangements envisaged for Canada spans private-sector involvement to outright divestiture. But the end product is clear: the "partnerships" are to be "the initial arrangement in an evolving relationship" intended to move government science facilities from "a joint sponsorship arrangement involving government to one in which the federal government is no longer involved in ownership, governance or management."

ISB symposium: update 2 [Discovering Biology in a Digital World]

Posted: 10 Oct 2008 02:07 PM CDT

The second speaker was Eric Davidson who talked about gene regulatory networks.

He works on sea urchins and showed us this amazing diagram that looked like a computer chip. The diagram describes the inputs and outputs of 50 genes during the first 30 hours of development.

And, it convinced me that systems biologists are developing their own language.

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ISB symposium: update 1 [Discovering Biology in a Digital World]

Posted: 10 Oct 2008 01:12 PM CDT

The first talk was by Irving Weissman, one of the pioneers in immunology and stem cell research. He talked about the stem cells that form blood, also known as HSCs or hematopoietic stem cells.

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Chili, capsaicin and cancer [Bayblab]

Posted: 10 Oct 2008 12:26 PM CDT

Speaking of the infamous journal "Medical Hypotheses", a paper published in 2002 tried to make a link between spicy food and stomach cancer:

"The 'hot' sensation produced by exposure to pepper is apparently due to two natural carcinogens: capsaicin in chili type peppers and safrole in black/white pepper. There are four cookeries in the United States that are noted for their high pepper content: Mexican-American, Cajun, white Creole, and black Creole. Each is largely confined to a single ethnic-cultural group which is concentrated in some counties. By use of county population and mortality data, significantly higher rates for stomach and liver cancer were found in counties inhabited by these four ethnic-cultural groups than in matched control counties."

Could it be true: chilies are carcinogenic? Might as well go to the source to find out, the country where chilies originated: Mexico. A Mexican study looking at associations between gastric cancers, chili consumption and H pylori infection found no independent association between the chilies and the Hp but a weak association with gastric cancer in heavy chili eaters (OR = 1.71; 95% CI = 0.76-3.88, p=0.026).

However there is mounting evidence that chilies may do more good than harm. Spices in general seem to make good candidates according to this recent review:

"the potential of turmeric (curcumin), red chilli (capsaicin), cloves (eugenol), ginger (zerumbone), fennel (anethole), kokum (gambogic acid), fenugreek (diosgenin), and black cumin (thymoquinone) in cancer prevention has been established."

You don't have to look very hard to find that in fact capsaicin has potential to inhibit the proliferation of cells in endometriosis , inhibit the growth of androgen-independent p53 mutated prostate cells, kill melanoma cells etc... The mechanism seem to included apoptosis, autophagy and ROS generation.

All this to say, you can eat your chilies without worrying too much about cancer, the harm done is mostly temporary and the jury is still out for the longer term...

Canadian scientists protest political interference [Bayblab]

Posted: 10 Oct 2008 12:22 PM CDT

The Canadian Scientist against the politicization of science sent an open letter to all the major party leader ahead of the election calling for an end to government interference in science. The letter is signed by 85 scientists, including a few from the University of Ottawa:

"Re: The Politicization of Science in Canada
Dear Sirs and Madam:
We are a group of concerned scientists writing to call for the end to the
politicization of science and related due processes in Canada. Below we highlight
some recent examples of the mistreatment of science in Canada:
• The closing of the Office of the National Science Advisor 1
• The misrepresentation of climate change science 1, 2
• The muzzling of Environment Canada scientists 3 4
• The cuts to and reorganizing of the Canadian Wildlife Service 5
• The political appointments to the board of Assisted Human
Reproduction Canada 6
• The halting of the Prison Tattoo Pilot Study and the suppression of the
results of this study 7
• The firing of the Head of the Canadian Nuclear Safety Commission 8
• The suppression and misrepresentation of research related to
Vancouver's Supervised Injection Site 9-11
The above represent blatant examples of instances when:
• Systems developed to provide non-partisan scientific advice were
undermined, interfered with, or dismantled for political reasons;
• Science was interrupted, suppressed and distorted for political reasons;
• Scientific uncertainty was manufactured in instances where none existed;
• Reputable scientists were attacked because the results of their work were
unpopular or inconsistent with the views of political parties;
While science is not the only factor to be considered in political decision-making,
ignoring and subverting science and scientific processes is unacceptable. In light
of these concerns, we are calling on all political leaders to articulate how they will
work to improve Canada's track record with respect to the treatment of science
and related due processes.
Yours truly,
Canadian Scientists Against the Politicization of Science"

Happy Birthday Lee Hood! Liveblogging the ISB symposium [Discovering Biology in a Digital World]

Posted: 10 Oct 2008 12:19 PM CDT

Right now, I'm sitting in the audience at a symposium on Science, Engineering, and Business at the Leading edge. The symposium is sponsored by the Institute for Systems Biology and it's Lee Hood's 70th birthday. Every speaker is beginning with a wish for a happy birthday.

I'll have updates, as I can, throughout the day.

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Parkinson's disease, GFP, and seeing the video in JOVE [Discovering Biology in a Digital World]

Posted: 10 Oct 2008 12:07 PM CDT

Sometimes words fail me. Luckily, we have videos.

Many of you have probably read about Roger Tsien receiving the Nobel Prize this work for his work with the green fluorescent protein (GFP), but I bet some of you are wondering, why a jellyfish protein is worth a Noble Prize.

jove_image.gifI think one of the best places to see why GFP is important, and also to see what some scientists do during the day, is JOVE, the Journal of Visualized Experiments.

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Science video of the day [Bayblab]

Posted: 10 Oct 2008 09:17 AM CDT


The most powerful and beautiful thing I have seen in science happened during my honors project. I had created transgenic zebrafish embryos expressing either GFP or a mutant DNA-methyltransferase fused to GFP (thank you nobel laureates). I then placed the embryos in a groove of agar and followed their development under the GFP scope taking pictures at regular intervals for about 36h. I guess we didn't have time lapse in those days. The great thing about zebrafish is that development is really fast, and the embryo is clear so you can see right through it. At 48h you pretty much have a fully-formed fish. I still remember vividly seeing the cell movements, the formation of the three germ layers, but most impressive I remember seing the heart starting to beat. I fell in love with development. This paper in science brings you this remarkable process in a convenient 1min video. It was done thanks to advances in imaging technology by fully digitizing images from scammed light sheet microscopy and tracking every nucleus of the embryo...

Live from CSHL [genomeboy.com]

Posted: 10 Oct 2008 09:02 AM CDT

I’m at the Personal Genomes meeting at Cold Spring Harbor. Maybe I’m jaded by now, but my expectations were low. I was wrong (admittedly it’s hard to know because they don’t give you an abstract book until you arrive). Watson gave his unique and pointed first-person history of the Human Genome Project, Francis Collins talked about finding rare and semi-rare variants (unemployment has been good for him), and Mary-Claire King gave an absolute tour de force on breast cancer as a paradigm for personal genomics. This morning Richard Gibbs reflected on Watson’s genome and Elaine Mardis talked about using Illumina sequencing to decode the first cancer genome. And it’s not even 10AM.

Around the blogs [Bitesize Bio]

Posted: 10 Oct 2008 07:19 AM CDT

Around the blogs this week: anti-social scientists, science grads who don’t know what a theory is and a system for handling difficult seminar questions…

How drug prices get high. Mike the Mad Biologist gets really mad about the way drug companies set drug prices.

Social networking - are we social enough? Jonathan Gitlin at Nobel Intent ponders whether scientists will buy into social networking, a timely article in light of the recent launch of the Small Worlds project.

Scientists who don’t know science. WritEdit at Medical Writing, Editing & Grantsmanship comments on a shocking study that showed a poor understanding of the basic principles of science among a group of graduates from an English university.

Aquoria victorious. Alex at The Daily Transcript was one of a few bloggers who picked up on the awarding of the Nobel Prize in Chemistry to the scientists who discovered GFP, but his excellent run-through of what makes GFP great makes this an article not to be missed.

and finally…

How to survive seminar questions. RMP at Evolgen came up with an excellent (funny) flow chart to help you when you get stuck with a question in your next seminar, inspired by the Sarah Palin debate flow chart apparently.

Quick Quiz: Are you competent to understand genomic tests? [Think Gene]

Posted: 10 Oct 2008 07:16 AM CDT

Solve this simple math question.

Statistics and disease risks are invented for this exercise!

1% of people will have Hubbub Disease by age 70. Up to 80% of people with Disease will get positive HEBOT mutation tests.  9.6% of people without Hubbub Disease will also get positive HEBOT mutation tests.  A patient had a positive HEBOT mutation test in genomic screening.  What is the probability that patient will have Hubbub Disease by age 70?

The correct answer is about 68.1%. If you got this, good job, you’re qualified, click here.

If you got a different answer or need an explanation, click here.

note: updated to be even more nonsensical to avoid confusion. Thanks, neandrothal.

Anti Cocaine, Heroin Test, and Excited Brains [Sciencebase Science Blog]

Posted: 10 Oct 2008 07:00 AM CDT

heroin-userThe latest issue of my SpectroscopyNOW column is now online. In this issue, having sampled a little cannabis chemistry last month, I turned to cocaine, and enzymes to beat addiction, and new techniques for testing the purity, or otherwise of street heroin.

Anti cocaine - A mutant enzyme that breaks down cocaine in the bloodstream 2000 times faster than the body’s natural enzymes could lead to a rapid-response treatment for acute overdose or lead to a new therapeutic approach to treating drug addiction.

Testing times for street heroin - Impure forms of illicit drugs are almost as big a problem as the drugs themselves. Now, researchers in Spain have used diffuse reflectance near-infrared spectroscopy (DR-NIR) to quickly determine the purity of heroin.

Sooty balloons - Nothing more sophisticated than a lump of graphite, a roll of sticky tape, and a wafer thin sliver of silica are needed to inflate ideas about nanochemistry. Raman spectroscopy and other techniques have been used to reveal the details of the DIY construction of a balloon-like membrane of graphene.

Stellar chemistry - Astroscientists are using various spectroscopic techniques to root out relatively complex molecules lurking in the interstellar medium. The complexity of naphthalene, discovered in space, and corannulene, could provide new evidence of a cosmic origin for the precursor molecules of life on Earth

Analytical compromise reveals protein folding secrets - A new X-ray technique, time-resolved wide-angle X-ray scattering (TR-WAXS) could defeat even high-field NMR spectroscopy in allowing researchers to monitor very fast, nanosecond-scale movements in the context of the overall three-dimensional protein structure.

Finally, this week, functional magnetic resonance imaging (fMRI) has revealed a reason why the excitement of unwrapping presents dwindles as our brains get older and more jaded. According to a new study, a biochemical pathway is responsible for mellowing our expectations. I cannot say I’ve noticed to be honest, I still get just as excited as the kids at Christmas unwrapping presents…although I’ve moved
on
from playing
with the packaging
I’ve moved on from playing with the packaging now.

Anti Cocaine, Heroin Test, and Excited Brains

Viral-based Human Disease and the Nobel Prize for Medicine [Highlight HEALTH]

Posted: 10 Oct 2008 03:56 AM CDT

nobel medal in medicineThe 2008 Nobel Prize in Physiology or Medicine was announced earlier this week. The prize was awarded to three europeans for the discoveries of two viruses that cause severe human disease; the cancer-causing human papilloma virus (HPV) and the human immunodeficiency virus (HIV).

Two French scientists, Luc Montagnier, age 76, at the University of Paris in Paris, France and Francoise Barré-Sinoussi, age 61, at the Institut Pasteur in Garches, France will split half the prize for their discovery of the HIV virus. Barré-Sinoussi is the 8th woman to receive the Nobel award for Physiology or Medicine.

A German researcher, Harald zur Hausen, age 72, at the University of Dusseldorf, Germany, will receive the other half of the $1.3 million prize for establishing that most cervical cancers are caused by two types of human papilloma virus.

The human immunodeficiency virus (HIV)

The HIV virus was identified in cultured lymphocytes (a type of white blood cell) from a patient with swollen lymph nodes, characteristic of the early stage of acquired immune deficiency [1]. While most oncogenic retroviruses induce cell growth, the HIV virus instead mediates cell fusion of T lymphocytes, impairing the immune system. A member of the lentivirus group, HIV RNA is converted to DNA and integrated into the T lymphocyte genome. The virus effectively evades the host immune system by continually changing and moving its genome from one location to another.

By 1984, Montagnier and Barré-Sinoussi had obtained several isolates of the HIV retrovirus from sexually
infected individuals, haemophiliacs, mother to infant transmissions and transfused patients. According to the Nobel committee, the discovery of the HIV virus made possible the rapid cloning of the HIV-1 genome that [2]:

… has allowed unravelling of important details of its replication cycle and how the virus interacts with its host. This led quickly to the development of diagnostic tools for identification of patients and screening of blood products, which has limited the spread of the pandemic.

Soon after the discovery of HIV, several groups presented evidence that HIV causes acquired human immunodeficiency syndrome (AIDS). The National Institute of Allergy and Infectious Diseases provides a comprehensive summary on The Evidence that HIV causes AIDS.

The CDC estimates that 1.1 million U.S. adults and adolescents were living with diagnosed or undiagnosed HIV infection at the end of 2006 [3]. For additional information on HIV prevention research and surveillance and the development of effective biomedical interventions to reduce transmission and HIV disease progression, see the CDC HIV/AIDS page.

The human papilloma virus (HPV)

HPV is a group of viruses that includes more than 100 strains or types. More than 30 types are sexually transmitted and can infect the genital area of men and women. In the 1970s, Harald zur Hausen postulated a role for HPV in cervical cancer [4-5]. Almost 10 years later, he identified human papillomavirus types 16 and 18 in two different human cervical carcinomas [6]. Since then, HPV16 and HPV18 have been found in ~70% of cervical cancers [7-8].

Sexually transmitted genital HPV infections are very common. Most occur without any symptoms and, over the course of a few years, go away without treatment [8]. However, some HPV infections persist for many years and are the primary cause of cervical cancer.

For additional information on HPV, including fact sheets, statistics, treatment guidelines and resources for clinicians and educators, see the CDC HPV - STD page. The National Cancer Institute also provides an informative fact sheet on the human papillomaviruses and cancer.

References

  1. Barré-Sinoussi et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983 May 20;220(4599):868-71.
    View abstract
  2. Advanced Information — The discoveries of human papilloma viruses that cause cervical cancer and of human immunodeficiency virus . The Nobel Prize in Physiology or Medicine 2008.
  3. Centers for Disease Control and Prevention (CDC). HIV prevalence estimates–United States, 2006. MMWR Morb Mortal Wkly Rep. 2008 Oct 3;57(39):1073-6.
    View abstract
  4. zur Hausen H et al. Human papilloma viruses and cancer. Bibl Haematol. 1975 Oct;(43):569-71.
    View abstract
  5. zur Hausen H. Human papillomaviruses and their possible role in squamous cell carcinomas. Curr Top Microbiol Immunol. 1977;78:1-30.
    View abstract
  6. Gissmann et al. Presence of human papillomavirus in genital tumors. J Invest Dermatol. 1984 Jul;83(1 Suppl):26s-28s.
    View abstract
  7. Muñoz et al. Against which human papillomavirus types shall we vaccinate and screen? The international perspective. Int J Cancer. 2004 Aug 20;111(2):278-85.
    View abstract
  8. Schiffman et al. Human papillomavirus and cervical cancer. Lancet. 2007 Sep 8;370(9590):890-907.
    View abstract
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This article was published on Highlight HEALTH.

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Framework for whole genome sequence analysis [Mailund on the Internet]

Posted: 10 Oct 2008 01:07 AM CDT

I’m working on a project right now where I am analysing a whole genome alignment of human, chimp, orangutan and macaque.

I’ve downloaded the alignment from the UCSC genome browser, it is in the MAF format, and I use the bx-python module from Penn State for the analysis. That is a very nice module, by the way.

For scanning through the alignment and collecting various statistics, MAF+bx-python is a fine combination, but now I have some interesting regions I want to analyse in more depth, and then the combination is not quite good enough.

The MAF files are essentially sequential chunks of alignments, and to find a particular region in the genome, I need to scan through a large file until I find the region.

I have solved this problem by extracting the regions and put them in a number of different files, that I can then easier access.  But wouldn’t it be nice if I could just seek() to the relevant position?  In any of the species coordinates just to make it even nicer?

The bx-python module lets me extract sub-alignments, so

s = a.slice(begin,end)

extracts the sub-alignment of a beginning at column begin and ending at end-1.

(I can also get a sub-set of species, if you are wondering, but the method is slightly different for that).

I would love to be able to get a sub-alignment based on species coordinates instead of column numbers, so

s = a.slice(begin,end,coordinates='hg18')

would give me the alignment that maches the region [begin,end[ in humans (hg18 assembly).  With a proper data representation, it should also give me this without scanning linearly through the file…

Does anyone know about a multiple alignment representation that lets me look up slices in files without scanning through all the alignment leading up to that location?

Surely genome browsers do not scan linearly through genomes to display their information — it would never be fast enough…

What do people use?

NPR interview with Douglas Prasher, the man who cloned GFP [The Daily Transcript]

Posted: 09 Oct 2008 02:57 PM CDT

Over the past two days, many have pointed out that the one person left out of the Nobel Prize was Douglas Prasher, researcher who cloned GFP from jellyfish, Aequorea victoria. Sadly, Prasher lost his funding and his lab just after he performed the ground work that led to Chalfie and (some of) Tsien's Nobel Prize winning work. It turns out that NPR recently found Prasher - he's now driving a bus in Huntsville, Alabama. Listen to the interview here. As one former colleague states, his case is an example of "a staggering waste of talent".

(ht: Abel)

For more on GFP, visit Marc Zimmer's History of GFP page.

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Road Trip: AB SOLiD Users Meeting [FinchTalk]

Posted: 09 Oct 2008 08:09 AM CDT

Wow! That's the best way to summarize my impressions from the Applied Biosystems (AB) SOLiD users conference last week, when AB launched their V3 SOLiD platform. AB claims that this system will be...

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