Sunday, April 27, 2008

The DNA Network

The DNA Network

A vaccine against lung cancer? [Discovering Biology in a Digital World]

Posted: 27 Apr 2008 05:50 PM CDT

A potential link between lung cancer and human papilloma virus may make parents even more glad about vaccinating their children with Gardasil®. Not only are the children protected against viruses that commonly cause cervical cancer, they may be protected against some forms of lung cancer as well.

The April 25th version of Nature News reports (1) that two viruses, HPV (Human papilloma virus) and measles virus, have been found in lung tumors.

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The human genome is old news. Next stop: the human proteome [Genetic Future]

Posted: 27 Apr 2008 05:39 PM CDT

Update: Hello reddit readers. If you're keen on human genetics/genomics, you can always subscribe to Genetic Future via RSS. You might also be interested in my posts on the elusive genetics of bipolar disorder, my explanation of why the hottest technique in human genetics (genome-wide association) is failing to capture most common disease genes, or my articles on the growing personal genomics industry.

Shameless self-promotion aside, let's talk about the human proteome.
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A Nature News article describes the initial plans for an ambitious effort to begin mapping the complete human proteome: the set of all human proteins expressed in all of our cells at all points during our development and adult life.

This is a project of vastly greater magnitude and complexity than the sequencing of the human genome. Unlike the genome, which remains essentially static between cell types and over time, the proteome is tremendously dynamic, changing constantly in response to cell-cell signalling and environmental stimuli. Thus even though -with some small exceptions - every cell in your body carries the same genome, the proteome can be wildly different between different tissues and can change rapidly over time (the image on the left is the result of proteomic analysis of a single tissue, the human kidney; each spot represents one protein). In addition, the function of proteins can change depending on where they localise within the cell, and which other proteins are around for them to interact with.

The complete mapping of the human proteome would require analysing the expression, localisation and interactions of all proteins in human tissue samples from all tissues at all stages of development, and following exposure to all possible forms of environmental stimulus. That's completely impossible with current technology, so the architects of the human proteome project have drawn up a more realistic wish-list:

The plan is to tackle this with three different experimental approaches. One would use mass spectrometry to identify proteins and their quantities in tissue samples; another would generate antibodies to each protein and use these to show its location in tissues and cells; and the third would systematically identify, for each protein, which others it interacts with in protein complexes. The project would also involve a massive bioinformatics effort to ensure that the data could be pooled and accessed, and the production of shared reagents.

It's unclear exactly which tissue samples will be used for the first phase of the project, but it appears that this stage will rely heavily on pooling data from pre-existing studies. After that, the project may move onto a detailed analysis of the expression levels, cellular localisation and interaction partners of proteins encoded by genes on chromosome 21 (the smallest human chromosome); alternative suggestions include a comprehensive analysis of all of the proteins found in a specific cellular location such as the mitochondria or the cell membrane.

There are some daunting technical obstacles to overcome for this project to be successful. Given that the project will be carried out by multiple laboratories around the world, there needs to be a serious attempt at standardising the protocols used to extract and characterise proteins. The article notes that "results from the Human Plasma Proteome project and other proteomics efforts showed that different laboratories — and even the same lab — often identify very different sets of proteins from exactly the same sample".

The project will be complicated by the fact that many genes encode for multiple different proteins, differing from one another in various regions, through a process known as alternative splicing. The proposed solution to that problem is to ignore it altogether:

[...] the group plans to focus on only a single protein produced from each gene, rather than its many forms. "We got rid of all this complexity," Bergeron says.

That may simplify the analysis, but it will also significantly reduce the power of the project. The single protein isoform selected by the project will not necessarily be the most important isoform produced by that gene (this is likely to differ substantially between different tissues). That means that the project will miss crucial information about the function of many of the proteins it analyses.

Actually, there are caveats of varying severity for nearly all of the currently available technologies for separating, identifying and characterising proteins. It's extremely difficult to develop methods that can accurately examine both low- and high-abundance proteins in a single run. Generating antibodies that reliably and specifically bind to each protein in the proteome will be a mammoth undertaking, and will be confounded by the alternative splicing issues mentioned above. High-throughput methods for detecting protein-protein interactions, while they have been used extensively (for instance in characterising the yeast protein interaction network), still suffer from a range of problems that can result in both false-positive and false-negative findings.

However, these are largely technology-driven constraints. Similar negative arguments were thrown at the human genome project, and look how that turned out! If anything, it seems likely that a proteome project of this magnitude would provide strong incentives to overcome the technical hurdles and standardisation problems that currently plague proteomics in general.

As a useful side-effect, this project (or its successors) will provide information that will help in interpreting the results of whole-genome sequencing. As I've noted before, we still know so little about our own genome that it's likely that most of us will have complete genome sequences well before we really have the tools and understanding to decipher what that sequence actually means. In order to have any chance of figuring out what effects a rare variant in an unannotated gene might have on our health we will need to call on data from many different fields of biology.

At the very least, large-scale analysis of the human proteome should allow researchers to tentatively place many of our currently anonymous genes into functional pathways. That's a step forward for personal genomics: knowing that you have a loss-of-function mutation in a gene that may be involved in cholesterol biosynthesis is a lot more useful (in terms of guiding further clinical testing) than simply knowing that you have a mutation in hypothetical gene C11orf68.



Subscribe to Genetic Future.

YouTube Channel of The Health Sciences Library [ScienceRoll]

Posted: 27 Apr 2008 02:19 PM CDT


Clinical Cases and Images shared this link with me. The Health Sciences Library of the University of Buffalo has recently started an own Youtube channel with a variety of tutorials and answers to FAQs. You can subscribe to it here.

At this point, there are 5 videos there:

This is a good example about how to educate with the tools of web 2.0 and how to get physicians, medical students or other medical librarians closer to your institute.

What’s on the web (2008 April 25) [ScienceRoll]

Posted: 27 Apr 2008 02:09 PM CDT


  • Mark McEwen, stroke survivor and former CBS Early Show co-host, will moderate a panel discussion on stroke on April 29, 2008 at 5:30 p.m. at the Hilton Chicago, 720 South Michigan Avenue, Chicago, IL. For those unable to attend the panel, a live webcast will be available.

Simulations and serious games have been employed for many years in the health industry. Because role-playing, labs, and clinicals have been a part of nursing and health education from the inception of teaching programs at hospitals, it has been a natural step to create CD-ROM simulations and to use videos and multimedia. The advent of workable virtual worlds that truly accommodate multiple users and are able to replicate the complexity of a real emergency room or even a home health care situation has the potential to revolutionize nursing and allied health education.

Gene Genie #30 at Gene Expression [ScienceRoll]

Posted: 27 Apr 2008 01:26 PM CDT


The jubilee 30th edition is up at Gene Expression. A great compilation of human genetics-related articles and blogposts.

It's the blog carnival of genes and gene-related diseases. Our plan is to cover the whole genome before 2082 (it means 14-15 genes every two weeks). We accept articles on the news of genomics and clinical genetics. The news and articles of personalized genetics are also included. Check out Gene Genie for more about this unique field of medicine.

gene_genie_logo_400.jpg
Many thanks to Ricardo Vidal for the logo!

Next edition is due to be published at Adaptive Complexity on the 11th of May. Don't forget to submit your articles via the official page.

Here are all the issues of Gene genie:

Hand versus brick. [T Ryan Gregory's column]

Posted: 27 Apr 2008 01:22 PM CDT

This is interesting. You know, in a "I kinda wish I hadn't seen that" sort of way...


Hat tip: Science After Sunclipse

What’s in your DNA? #28 [Eye on DNA]

Posted: 27 Apr 2008 12:14 PM CDT

The DNA Restaurant in Old Montreal, Quebec Canada isn’t really named after the DNA we like best.

Though the name may have you conjuring up medical reports and murder trials, DNA actually stands for Derek ‘n’ Alex, Derek being Dammann, and Alex being Alex Cruz, the suave maitre d’ and resident wine expert. (The Gazette)

dna no drinkingLee at Tokyo Times reports from Japan on a collection of coasters that tell people you’re not into downing alcoholic drinks in one gulp. One of the coasters says:

I can’t drink - it’s not in my DNA.

Danielle Parsons at Am I There Yet? is challenging herself to accomplish 101 things in 1001 days:

So no more someday (which, presumably, is the day that I'll get there). I may not be able to radically overhaul of my life, and quit procrastinating on everything that I want to do (anyone who knows me well knows procrastination is embedded in my DNA) – but I am going to do 101 things in 1001 days.

Go Habs Go [The Daily Transcript]

Posted: 27 Apr 2008 08:39 AM CDT

It is interesting how different corners of the world are preoccupied by unique items of interest. Take Montreal, my "home town". There is a long history of hockey here and recently the whole town has gone Berzerk. You see unlike Boston and the Red Sox, Montreal not only has a historic team, but everyone here knows a hockey player. For example the great Mike Bossy went to my high school (note that he never graduated). After leaving the Montreal Suburbs, he played with the NY Islanders and won four consecutive Stanley Cups with them. Unfortunately he had to retire extremely early due to a bad back.

It's been 15 years since the Canadiens won the Stanley Cup and this year the Habs have a great team. You might be wondering Habs? Whao are they? Once upon a time the Canadiens were known as Les Habitants, or Habs for short they then changed their name but have kept a small "H" in their logo that serves as some sort of vestigial appendage.

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Kwäday Dän Ts’ìnchi - "Long-Ago Person Found" [The Genetic Genealogist]

Posted: 27 Apr 2008 05:00 AM CDT

image Around the year 1700, a relatively healthy young hunter was walking along a glacier in land that would one day be British Columbia in Canada. He wore a robe of 95 animal skins, perhaps gopher or squirrel, stitched together with sinew, and carried a walking stick, iron-blade knife, and spear thrower. For some reason, the young man, aged 17 to 22, died on the glacier and was quickly incorporated into the ice. There he remained, frozen, for the next 300 years.

In August 1999, three hikers noticed a walking stick, fur, and bone lying on a melting glacier (60′ N 138′ W). The young hunter, renamed Kwäday Dän Ts'ìnchi in the Southern Tutchone language of the Champagne and Aishihik First Nations, was removed by scientists for analysis (see the NY Times article, and the Journal of Canadian Archaeology article). From an article in the Sydney Morning Herald:

[When scientists were led to the site], they found a torso with the left arm attached. The hand was mummified. The fingernails were missing. The head was missing, too. A few metres away lay the lower body, with thighs and muscle attached. They also found a wooden dart and walking stick, and pieces of fish and scales within the folds of the man’s robe.

Over the next two days the team members carefully lifted the remains. They collected a knife still in its sheath and a leather pouch. They found a woven hat, fragments of clothing and what was later described as the man’s “personal medicine bag”, which was considered sacred, even after more than five centuries. They did not open it.

In 2001, Kwäday Dän Ts'ìnchi’s remains were given back to the Champagne and Aishihik, and in July 2001 he was cremated in a closed ceremony and returned to the glacier. Kwäday Dän Ts'ìnchi’s skull was found in 2003 but was not removed from the site.

Discovery Continues

Even though Kwäday Dän Ts'ìnchi has been cremated, the analysis of his DNA, intestinal contents, and artifacts continues. This past weekend, at the Kwäday Dän Ts'ìnchi Symposium, researchers around the world presented the results of their research:

The conference brings together more than 30 researchers from fields as diverse as archeology, criminology and microbiology. They come from local universities, the Royal B.C. Museum, Vancouver General Hospital, first nations, and institutions as far afield as Indiana and Scotland.

Haplogroup A

One of the research projects involved sequencing of Kwäday Dän Ts'ìnchi’s mtDNA, which revealed that it belonged to Haplogroup A, with the polymorphisms 16111T, 16189C, 16223T, 16290T, 16319A, and 16362C. As part of the study, the researchers collected blood samples from 250 to 300 members of the Champagne and Aishihik First Nations to compare their mtDNA sequence to that of Kwäday Dän Ts'ìnchi’s (more info here and here). At the Symposium, the researchers revealed that 17 people had mtDNA that closely matched that of the subject, suggesting that they are close maternal relatives. 15 of those 17 people belong to the Wolf clan, also suggesting that Kwäday Dän Ts'ìnchi might have belonged to the Wolf clan himself (more info here).

This topic is of particular interest to me, since my mtDNA belongs to Haplogroup A and therefore I am also (very) distantly related to Kwäday Dän Ts'ìnchi. Last year I profiled the Qilakitsoq mummies in Greenland, all of whom belonged to Haplogroup A.

HT: Geneasofts

Let's give everyone Beta Blockers in Heart Failure! [The Gene Sherpa: Personalized Medicine and You]

Posted: 26 Apr 2008 06:12 PM CDT

Ok, So some people have been talking about this wonderful polymorphism in African Americans. This polymoprhism is in the GRK5 gene. What does it do? Well, before I look at any polymophism I always...

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