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Personal Genome Sequencing


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#31 kevin

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Posted 10 October 2005 - 07:12 PM

Link: http://www.nature.co...ll/437796b.html


Published online: 5 October 2005; | doi:10.1038/437796b
Japan jumps towards personalized medicine
Desktop-device uses advanced DNA chip to analyse patient's blood.
David Cyranoski


Japanese companies say they have built a desktop machine that will allow doctors to assess patients' DNA from a single drop of blood, and so tailor treatment to an individual's genes. The machine can deliver results within an hour, they say, and will be on sale for 5 million yen (US$44,000) by autumn 2006.

Safe dosage, effectiveness and side effects for any given drug vary from patient to patient. And determining which drug and dosage is best for any given individual is a critical challenge facing healthcare specialists.

But the announcement about the Japanese machine on 27 September came just a week after scientists in the United Kingdom spoke out against the hype surrounding personalized medicine. A report produced by the Royal Society warned that prescriptions tailored to a patient's genes are at least 15 to 20 years away.[lol]

The Japanese device was developed by the genomics facility of the Institute of Chemical and Physical Research (RIKEN) in Yokohama, the printing company Toppan in Tokyo, and the Kyoto-based maker of scientific equipment Shimadzu. Shimadzu's Takaaki Sato, who led Shimadzu's development efforts, says the key advance is a chip that analyses DNA in a blood sample, thereby bypassing the time-consuming DNA purification steps currently needed.

Although Sato will not give further details, he says that any health worker could use the machine to test a drop of blood for a particular genotype, and get a result in an hour. "Patients do not want to wait a week or even a day for results before being able to take a medicine, especially if they have an infectious disease," says Sato.

According to RIKEN and Shimadzu, the machine will first be tested on patients being prescribed one of two medicines: an antibody called irinotecan, which can cause hearing loss in people with a certain mutation in their mitochondrial DNA, and the anticoagulant warfarin, which causes excessive bleeding in some patients.

But there is scepticism over how useful the device will be. David Weatherall of the Weatherall Institute of Molecular Medicine at the University of Oxford, UK, who worked on the Royal Society report, says the metabolism of warfarin is related to at least two genes whose interaction is not understood. Other factors, such as the patient's age or additional drugs being taken, also need to be considered, he says.

"There is no way around these problems except to test each drug independently in large population studies, and to monitor all these issues over several years," he says. "There is still a huge gap between the scientists who do this kind of work and its application for practical purposes."

Sato admits that initially his machine will be most useful for research. But judging from the "unbelievable number of responses" received since announcing the test, he says there is no way that 15 years will pass before doctors are using such devices for day-to-day diagnosis and treatment.

#32 manofsan

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Posted 10 October 2005 - 08:26 PM

hi scottl & kevin,

scottl I'm not sure how your article relates to the nature article that kevin posted. SNPs are important, but that japanese chip sounds like it can read the entire genome, and not just SNPs.

can anyone please comment on how the japanese chip works? is it just another gene array chip? when they are claiming to read your entire genome in an hour based on a blood sample, that's a very ambitious claim.

as for the political argument that personalized genomic data won't immediately lead to personalized treatments -- fine, there's nothing new in that argument, we've heard that before. what matters is that as such machines/technology gets into the marketplace and comes into widespread use, then the timetable for realization of personalized treatments will be accelerated.

what I'd really like to hear about is how technically sound the genome-sequencing from this technology is. how qualitatively strong are the results?

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#33 Lazarus Long

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Posted 10 October 2005 - 08:57 PM

This is part of the subject of today's All Things Considered on NPR that I am listening to right now.

I will check my pod catcher to see if it is there in MP3 format so as to upload it.

DNA Advances: The Machinery Behind Human Beings
Audio for this story will be available at approx. 7:30 p.m. ET

All Things Considered, October 10, 2005 · DNA tools continue to improve in their ability to determine details of a person's genetic make-up. NPR's Robert Siegel and Joe Palca survey the latest developments in the field.



#34 manofsan

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Posted 11 October 2005 - 01:32 AM

Hi Laz,

I listened to the podcast, but it didn't mention anything about the Japanese desktop genome sequencer. The mention of the various internet/mail-order DNA analysis companies was interesting, though.

#35 Lazarus Long

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Posted 11 October 2005 - 01:58 AM

They never really got into it but in the lead up they mentioned the new technology being developed and I thought they were going to get into greater depth but in the end they didn't.

There is no doubt a lot beginning to get out on this and many related subjects. Two articles in the NY Times today about Stem Cells and how IBM wants to protect the privacy of the genetic data of their employees.

#36 John Schloendorn

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Posted 11 October 2005 - 08:18 AM

Japanese desktop genome sequencer

Not sure from where you've got the idea that this would be a desktop genome sequencer, in the sense of a small machine that can rapidly sequence a whole genome all by itself. Nobody ever said so.

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#37 kevin

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Posted 11 October 2005 - 01:03 PM

I don't think this is a genome sequencer. It sounds to me that it is possible that it will detect SNP's of specific genes using hybridization, which doesn't take as much in the way of technological advances.

#38 zerowave

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Posted 27 February 2006 - 06:04 AM

What a great thread!

Edited by halcyon, 21 April 2006 - 09:13 PM.


#39 zerowave

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Posted 27 February 2006 - 06:13 AM

A little old, but still tracking the history well I think.

Technology
Speed reader
Robert Langreth, 11.11.02

Craig Venter sequenced the genome in record time, ushering in a new era of drug discovery. Next step: fast, cheap scans of your DNA that you can take home.
The gene guru J. Craig Venter stunned the scientific world in 2000 when his company, Celera Genomics, deciphered the entire human genetic code in little more than two years with an R&D Budget of $270 million. A consortium of U.S. government researchers took 13 years and spent $2.5 billion to reach the same finish line. (The government says it spent only $300 million on the actual sequencing of the genome.)

But Venter says that even his rapid-fire breakthrough didn't come nearly fast enough. He used 300 high-speed DNA-sequencing machines, which cost $300,000 apiece, to map the human genome. He dreams of a day, a decade or more away, when doctors will routinely and rapidly churn out the individual maps of thousands of patients, spotting the genetic errors that cause an array of dysfunctions or diseases.

The problem is that one sequencer operating around the clock takes at least three years to crank out the raw unordered genetic code of just one person. "There's no way that existing machines will get us where we need to go," Venter says.

Now his mission is to get as much human DNA read as fast as possible. Venter left Celera in January and is outfitting a new $30 million nonprofit sequencing lab in Rockville, Maryland, to be funded by government grants and his own foundation. In the next few years he plans to decode the key portions of the DNA of a thousand individuals of various nationalities and ethnic groups, at a cost of $500,000 each. Donors with the cash to help out are welcome.

Initially Venter will do the sequencing on existing machines optimized for speed, but he has a bigger goal in mind: to hasten the arrival of a new generation of ultrafast sequencers that can read the genome far faster at far lower cost. He predicts that within ten years, before a newborn leaves the hospital its entire genome will be burned onto a DVD, which will be given to the parents along with its birth certificate.

Every time a new gene is linked to a disease, people will be able to search their genomes using their home personal computer to learn whether they are at risk so that they can decide what, if anything, to do about it. "I want to make the genomics revolution meaningful to ordinary people," Venter says.

He hopes to stimulate the efforts of a group of tiny biotech companies that are developing high-speed gene-scanners in the same way that his work at Celera Genomics forced the government's Genome Project to accelerate its efforts.

The new startups, which include Perlegen Sciences in Mountain View, California; U.S. Genomics in Woburn, Massachusetts; 454 Corp. in Branford, Connecticut; and Solexa in Cambridge, England; aim to use recent advances in nanotechnology to decipher mysteries at the amino acid level.

"I use other people's technology to drive the science that I want to do. The science I do helps, in turn, to drive the technology," Venter says. "It is like working up a ladder." He has always thrown himself into his work: Venter recently revealed that one of the five different DNA samples used by Celera to map the genome was his.

The epochal breaking of the human code was only a start. Knowing the sequence of one genome isn't enough; what matters more is knowing the differences among thousands of genomes. Only by understanding the subtle genetic variations in hundreds of thousands of people--by sifting out the molecular misnomers that predispose someone to a specific malady--will scientists learn how to better predict, diagnose and ultimately cure such difficult diseases as diabetes, schizophrenia and heart failure.

continued here: http://www.forbes.co...2/1111/068.html
Speed reader - Forbes.com

#40 zerowave

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Posted 27 February 2006 - 06:33 AM

http://www.thepersonalgenome.com/
a blog on articles and events related to personal genome sequencing (as the name implies)

http://www.pwc.com/t...armaco-wb-x.pdf
a good perspective from pharmaceudical companies' point of view.

#41 zerowave

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Posted 08 March 2006 - 04:52 PM

This last paragraph I think is a clear introduction to why a fast genome sequencer is needed. We can't determine the differences between people's genes very easily (it is extremely difficult and time consuming for even the simplest cases!). Having millions of genome sequences in hand would make correlation a ~simple task.

How might the Human Genome Project and genomics research help us understand the aging process?

Controversy has long existed in scientific circles as to the precise roles genetics or environment play in the aging process and the determination of potential life span. When reduced to the level of the cell, life span does seem to be genetically determined. Healthy, non-cancerous somatic (or body) cells placed in tissue culture in the laboratory will undergo a defined number of divisions or replications, and then they stop reproducing, entering a senescent phase. The number of divisions a cell can undergo is determined by its genes. Of course, there are also non-genetic influences on cellular aging. For example, free radicals, byproducts of the body's natural metabolism of oxygen, wreak havoc with cells' DNA in a process called oxidative damage. Exposure to radiation is another example.

Research on Lower Life Forms and Aging
Work done on some of the lower life forms whose genomes have also been sequenced has contributed much to scientists' understanding of normal aging. Caenorhabditis elegans, the roundworm, is one of the organisms whose genome has been fully sequenced. Scientists have found that manipulating daf-2, a gene involved in the roundworm's insulin signaling pathway, can increase its life span in the laboratory three- to five-fold. A gene mutation called Methuselah in the fruit fly Drosophila melanogaster, another organism whose genome is sequenced, can increase its life span by 35%. While humans share many genes with these other life forms, we also have a far more complex genetic structure.

Genes and Human Longevity
How much of our longevity is determined by our genes is undergoing intensive study. Scientists have known for several years that people who live the longest often have very long-lived children. Adoptees' life spans are more closely correlated to those of their birth parents than to those of their adoptive parents.

We can inherit one of several different forms of a given gene, depending on what forms our parents carry and then pass on to us. Some of these gene variants are associated with a shorter life span because they are linked to certain diseases, such as the BRCA1 and BRCA2 genes of breast cancer and apoB, which is associated with high blood levels of cholesterols. Variants of other genes have been associated with longer life spans, and inheriting these increases our likelihood of achieving greater longevity. These seem to be related to a number of age-related diseases and conditions and are often referred to as "longevity assurance" genes. These include variants of apoE, ACE, HLA-DR, and PAI-1. New research that studied the genes of sibling pairs who reached extreme old age also suggests that an additional gene or genes on chromosome four may also confer longevity assurance.

Challenges Ahead
This research is exciting, but it is still in its infancy. To determine whether a particular gene causes a disease (or longevity) and how is not an easy task. In the case of a disease, for example, scientists must have a clear understanding of just how the disease causes damage, which is not always that obvious. The gene believed to be responsible for that disease must have been clearly identified and cloned (reproduced for study purposes). Finding what portion of that gene contains the variant sequences that might cause a given disease is also complex, because so much of the specific sequences of genes is still not known. And if by some lucky chance, scientists do identify a gene with an obvious variant that appears to cause a particular disease, they need a large enough population of people with that disease and gene to make the results of studies statistically valid.

from: http://websites.afar...A_b_human_4_how
AFAR: The Human Genome Project and the Aging Process

Edited by halcyon, 09 March 2006 - 04:10 AM.


#42 John Schloendorn

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Posted 09 March 2006 - 03:36 AM

a fast genome sequencer is needed

I completely agree. Being able to compare hundreds of individuals' genomes and their aging pathologies would likely be massively beneficial in terms of both understanding and intervention. What we need now is a "how". In what ways might the the average immortalist be able to significantly accelerate the advent of fast and cheap human genome sequencing?

#43 kevin

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Posted 09 March 2006 - 08:11 AM

I think promoting the development of therapies for genetically diagnosed diseases would go a long way to increasing the perceived value of personal genome sequencing.

Withough cures to go with the sentences of death and/or disability which these diagnoses often bring, people are not interested in knowing if they will suffer from them and the money spent on the development of such tests is viewed as better spent elsewhere.

Thus, as is my mantra, becoming a credible source of information and actually "promoting" that information wherever possible in terms of fostering hope for the future through scientific progress, is what the average immortalist should likely be doing.

btw.. is there really such a thing as an average immortalist.. ?

#44 zerowave

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Posted 09 March 2006 - 06:30 PM

Great review of most of the current efforts:

Advances in sequencing technology
Eugene Y. Chan

From introduction:
With “personal genomics,” a term that describes individual access to their own genome sequence information, on the horizon, it is apt to summarize the efforts of the groups who are going to make this become a reality. This paper is intended to review the state-of-the-art for Sanger-based methods and also progress for new methods, those that do not rely on electrophoretic separation of Sanger dideoxy reaction products. This is neither intended to summarize new developments related to the Sanger method, describe the ethical, legal, and societal implications (ELSI) of personal genomics, nor expound on the potentialworldly and otherworldly impact of such a technology paradigm shift; instead, this review will present a thorough and detailed analysis of each method’s technical status, its strengths and weaknesses, and its remaining challenges.


Abstract
Faster sequencing methods will undoubtedly lead to faster single nucleotide polymorphism (SNP) discovery. The Sanger
method has served as the cornerstone for genome sequence production since 1977, close to almost 30 years of tremendous
utility [Sanger, F., Nicklen, S., Coulson, A.R, DNA sequencing with chain-terminating inhibitors, Proc. Natl. Acad. Sci. U.S.A.
74 (1977) 5463–5467]. With the completion of the human genome sequence [Venter, J.C. et al., The sequence of the human
genome, Science 291 (2001) 1304–1351; Lander, E.S. et al., Initial sequencing and analysis of the human genome, Nature 409
(2001) 860–921], there is now a focus on developing new sequencing methodologies that will enable “personal genomics”, or the
routine study of our individual genomes. Technologies that will lead us to this lofty goal are those that can provide improvements
in three areas: read length, throughput, and cost. As progress is made in this field, large sections of genomes and then whole
genomes of individuals will become increasingly more facile to sequence. SNP discovery efforts will be enhanced lock-step with
these improvements. Here, the breadth of new sequencing approaches will be summarized including their status and prospects
for enabling personal genomics.

Attached Files


Edited by halcyon, 09 March 2006 - 09:37 PM.


#45 JonesGuy

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Posted 09 March 2006 - 08:19 PM

John, I've read a few times that the reagents are half the cost of a genome sequencing.

It seems to me that getting involved in the reagent business might do quite a bit to bring down the cost. Encouraging the production of reagents, attempting to cut costs in delivery, etc. This is a potential start up company that might pay off quite big, since reagent demand will go up as price comes down.

#46 zerowave

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Posted 09 March 2006 - 08:44 PM

QUOTE (John Schloendorn)

I completely agree. Being able to compare hundreds of individuals' genomes and their aging pathologies would likely be massively beneficial in terms of both understanding and intervention. What we need now is a "how". In what ways might the the average immortalist be able to significantly accelerate the advent of fast and cheap human genome sequencing?


A difficult question, and one I'll have to think much more about. Possible options are:
Directly funding small research groups (this would definetly be a good general way for anyone with a few bucks to help).
Working for a group indirectly, by providing current and relevant research papers or tracking down references at university libraries.
Working directly in a lab.
Collaborating. Using their expertise to help solve critical steps in others' existing research plans

A good question though, and I'd be very curious to hear other suggestions.

QUOTE
kevin: I think promoting the development of therapies for genetically diagnosed diseases would go a long way to increasing the perceived value of personal genome sequencing.


I think by the number of articles out there, and people and companies working on this, that it is fairly widely recognized that this would be valuable. But there is definitely room for more! I think you posted it before that the NHGRI (a division of NIH) has awarded two rounds of grants (2004: http://www.genome.gov/12513210 and 2005: http://www.genome.gov/15015202 ), and is soliciting more proposals for this coming year ( http://www.genome.gov/10000368#5 ). In addition to the public groups there are plenty of private ones.

Still, there should be parades and marches for personal genome sequencing. This will make massive strides towards curing those other marchable goals like aids, breast cancer, muscular dystrophy, as well as every other disease, including aging.

Edited by halcyon, 21 April 2006 - 09:15 PM.


#47 zerowave

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Posted 09 March 2006 - 08:55 PM

John, I've read a few times that the reagents are half the cost of a genome sequencing.

It seems to me that getting involved in the reagent business might do quite a bit to bring down the cost.  Encouraging the production of reagents, attempting to cut costs in delivery, etc.  This is a potential start up company that might pay off quite big, since reagent demand will go up as price comes down.


Yeah, they mention that in this attached article from scientific american, and in many others. This is the reason that many groups are working on single molecule methods, and picoliter containers for doing reactions.

Attached Files



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#48 kevin

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Posted 21 April 2006 - 07:53 AM

http://www.newscient...id=CPNCPLANHMMF

Very cool..



Genome-in-a-day promised as DNA is put through hoops
11:15 17 April 2006
Andy Coghlan


Rapid genome sequencing

IT TOOK a decade of hard slog to produce the first, momentous read-out of the human genome, but researchers think they will soon be able to do the job in a day.

An instrument capable of reading thousands of DNA fragments per second is being developed by researchers led by Tony Bland of the Cavendish Laboratory at the University of Cambridge. The concept behind it was unveiled last week at a briefing in London.

“The system could read thousands of DNA fragments per second ”Reading a person's genome in just a day brings closer the possibility of cheap, personalised sequencing to reveal gene variants that might lead to disease. Individuals might be able to forestall any genetic predisposition to illness by changing their lifestyle. One of today's most advanced instruments working full-time would take around 27 years to complete the task, says Tony Smith of Solexa, a genome-sequencing company in Cambridge, UK. "This new method seems compelling." For now, though, the "genome in a day" technology is still in the lab, and is unlikely to be commercially available for five to 10 years.

As with existing methods, the DNA to be sequenced is first broken into small overlapping fragments that can be reassembled in order once the sequence of DNA bases on each fragment is known. Traditionally, each DNA fragment in a sample is identified using a chip coated with "bait" fragments of known, complementary sequences. If a target sequence is captured from the sample a visible signal, usually from a fluorescent dye, is emitted. Because each different bait molecule is located at a precise location on the chip, a sensor can work out from the fluorescent signals which sequences from the sample have been caught. The speed of the process is restricted by how fast the chips can be read.

Bland's technology employs the same principle, except that the bait molecules aren't stuck to a chip. Instead, each one is attached to a magnetic particle that has its own specific binary magnetic code. When the baited magnetic particles are mixed with the DNA fragments, any complementary sequences bind together.

Each particle is a stack of nickel or ferromagnetic metal alloy discs 2 micrometres in diameter. The stacks would typically be no more than 10 micrometres high, and the fluorescent bait would be linked to the top disc. Each disc provides a "bit" of information in a binary code, creating a string of 0s and 1s to give the entire stack its unique code.

Once the target fragments have been trapped by the bait molecule, causing the fluorescent dye to glow, the particles are passed one at a time through a microscopic hoop exposed to a magnetic field. As each magnetic stack passes through, its pattern of magnetic 0s and 1s can be read by measuring their effect on the applied field. Then it is simply a matter of measuring only the glowing particles. "You could send 1000 through per second, and have parallel channels operating at the same time," says Bland.

To sequence the human genome, Bland estimates that you would need to prepare 4 billion particles with unique bait sequences and binary codes - a huge number, but the system offers effectively limitless capacity to pre-assign codes to the particles. Bland calculates that you could achieve genome-in-a-day capability with stacks of just 32 discs, each stack providing a binary code 32 digits long.

Although the first commercial instrument is likely to cost over £1 million, the price should come down rapidly if it is mass-produced, he says.




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