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A DNA Sequencer Cheap Enough For (Some) Doctors' Offices
cylonlover writes "Until recently, DNA decoding machines — fitting in the US$500,000 to $750,000 price range — would take weeks or even months to sequence a human genome, and the whole procedure would cost $5,000 to $10,000. That could be about to change, however, as Life Technologies introduces the Benchtop Ion Proton Sequencer — a machine that may finally deliver the power of genetics into the hands of ordinary doctors thanks to its $149,000 price tag and ability to decode a human genome in one day at a cost of $1,000."
Warning--side effects may occur.
I predict that the first buyers will be University research hospitals, and the Mayo Clinic.
It needs to drop a bit more before seeing it at your local pediatrician's.
There are two unfortunate challenges that the Ion Proton approach hasn't yet solved. The first is that the steps required to get the DNA out of human cells and into the sequencer (DNA extraction and especially library preparation) are still frustratingly complex. Their OneTouch device simplifies parts of the library prep but there are still many steps that require highly skilled people doing hours to days of work.
The second major issue is that the genome is being read out in fragments of 200-400 nucleotides, then needs to be assembled. The human genome is full of repetitive regions that are much longer than 200-400nt and when one gets a sequence read from one of these regions, it's can be very difficult to determine which of the copies of the repeat region that sequence came from. Better statistical models and algorithms for genome assembly may solve this to some extent, but there are fundamental limits to what can be done with short sequence reads. Other sequencing technologies don't suffer the short read problem, Pacific Biosciences' hardware for example can read several thousand nucleotide fragments. Mate pairing strategies might be used on the Ion instrument but the library prep for these involves considerably more challenging and manual lab work.
Not to demean this excellent advance in the technology but it should be called out that the pace of understanding what all these raw sequences mean is not on a growth path too. Anyone have some ideas for accelerating our understanding of semantics?
It really is a daunting task. The protein codings are just the beginning. We are making some progress on the various (more to come?) regulatory mechanisms and from there we need to know how all of that interacts over the lifetime and various differentiate cell states. Throw in environmental factors and wow, that's a big space to map out. It needs automation but how?
The Ion Proton Sequencer uses analysis software called Ion Reporter to analyze the data of a single genome on a single server. This speeds up the process considerably and removes the IT-related bottlenecks
Genius! A cluster of computers is an obvious bottleneck and they have made the step of getting a single server to do all the work. I hope they have a patent on that idea.
However, the most important factor in reducing the sequencing speed so dramatically is the introduction of the next generation of Ion Torrent semiconductor chip technology.
Oh. Right. So this is really just using _better_ hardware to do the job.
A hundred and fifty grand doesn't sound like a whole lot of money for medical equipment.
-jcr
The only title of honor that a tyrant can grant is "Enemy of the State."
Doctor: "Well, it looks like you have a common cold. But let's be sure, shall we? I just got this new DNA sequencing machine. Come back tomorrow."
The next day...
Patient: "Hebho bhoctor, bhat dho I habh?"
Doctor: "Well, it looks like you have a common cold. That will be $1000."
Yes, you bring your doctor a thumb drive with 3 billion base pairs of your genome, coding for 23,000 genes. Do you know what he says?
"What am I supposed to do with that?"
Years ago, people thought that we could find Mendelian genes for all the important things in health and disease. Now it turns out that most of the important things we want to know are controlled by hundreds or thousands of genes, each of which increases the risk by 1%, sometimes less. That's for things like cholesterol, autoimmune diseases, cancer susceptibility, etc.
For the most part, your family history is a better predictor than any genome screening. Gene tests usually aren't useful unless you have a particular gene in your family and you want to find out whether you have it, like the BRCA genes for breast cancer. If your mother died of breast cancer at age 40 because of the BRCA1 gene, and you don't have the BRCA1 gene, you don't have to worry.
The term "junk DNA" is now only used by shoddy science journalism. We're quite comfortable with how DNA and RNA do what they do. There's a mystery about what happens on the protein side, and the question about what functional bits of RNA (called microRNA) interact with what genes is sheerly a matter of ridiculously obtuse combinatorics. Say whatever else you will about them, fat cancer research budgets have taught us a lot about the essentials.
Bio questions? Ask me to start a Q&A journal. Computer analogies available for most topics!
just wtf is an "ion proton"? a proton is an ion. so what then is an ion proton? a $150,000 benchtop 1 day human genome sequencer and marketing couldn't come up with a better name? or at least a more correct one like "proton ion".
I am a biologist. Ask me questions in my journal. I'll give car/computer analogies if possible!
No need for the invite. This is Slashdot. You had us at "Samantha".
Set your phasers on "funky"!
I know someone who (was) married to a guy who's only 26 and he makes six figures selling some sort of medical machine. Apparently he plays video games all the time and is lazy and just works sparingly and travels a few times a month. You have to wonder about how much mark up is on these medical machines if a guy who works only only a few days a week or month with little schooling can earn 6 figures in commissions
What kinds of nefarious outcomes can this technology lead to? Insurance companies and DHS using it in ways that help no one but themselves (and the children) immediately come to mind.
FTFA: "However, the most important factor in reducing the sequencing speed so dramatically is the introduction of the next generation of Ion Torrent semiconductor chip technology."
Shouldn't it be increasing sequencing speed, or reducing sequencing time?
I read Slashdot for the headlines, because the headlines, unlike the articles, are usually original and never duplicated
Can they help us crack Photosystem II? That bastard is frustrating chemists the world over (as far as knowing sort of how it works but not enough of the really key details).
Now my doctor can make some interesting mutant fish for the aquarium in his waiting room..
we are about to be served with a "let's look at your DNA" at every visit for completely unrelated diseases in every possible scenario possible. This is going to get annoying very fast
Never antropomorphize computers, they do not like that
Just curious since I remember reading, admittedly on a blog, somebody take that "It takes X dollars to do 1 MRI" statement on. Basically the idea was that MRI's have a huge fixed cost. (IE you have to pay for the machine and tech before you do even the first MRI) However the additional cost from each MRI was basically nothing.(Since the machine has to be already there, it's going to use the same amount of power no matter what and the tech has to be there.) So from an economic point of view it didn't make sense to put a huge cost on each individual MRI since that would encourage docs to not use the machine. (When they really should try to schedule as many as possible since each one was additonal money and didn't really cost anything.) Is the deal the same with this sequencer? (IE once you have the machine and the guy to run it a single sequence basically costs nothing.)
Did you know 80 to 90% of the moderators on slashdot wouldn't recognize a troll even if one dragged them under a bridge.
'Is the deal the same with this sequencer? (IE once you have the machine and the guy to run it a single sequence basically costs nothing.)
No, the $1000 (or whatever the figure turns out to be) is just for consumables. You need to spend this on every run.
Just curious since I remember reading, admittedly on a blog, somebody take that "It takes X dollars to do 1 MRI" statement
The DNA sequencing table shows a precipitous drop in costs down below $10,000 and under .10 per genome or check the latest genome chart. However this cost only calculates raw full human sequence not just a particular strand or some desktop device that does limited work.
When the foot seeks the place of the head, the line is crossed. Know your place. Keep your place. Be a shoe.
Thanks for the info, ignorance fought
Did you know 80 to 90% of the moderators on slashdot wouldn't recognize a troll even if one dragged them under a bridge.
I'll add a clarification about Junk DNA for non-biologist slashdotters:
Although some may use the term 'Junk DNA' erroneously, as analagous to 'DNA with unknown function', this does not mean that the term is not valid. In fact, most of the human genome is certainly junk, in the sense that it demonstrably has no function whatsoever. For example, approximately one-third of the genome is made up of many thousands of copies of long-dead transposable elements (known as LINES and SINES; look them up). A further 10% of the genome is made up of other nonfunctional transposable elements, and about 8% is made up of dead viruses. Much intronic sequence is also junk.
While it has long been understood that some of the 98.5% of the genome that is non-coding DNA is functional, this only represents a small fraction of total non-coding DNA, and in invariably located within the ~10% of the genome that is evolutionarily conserved. This 10% figure also constitutes the most plausible upper limit for functional DNA.
In summary, the current figures we have are that two-thirds of the genome is known to be junk, less than 9% is known to be functional, and almost all the remaining fraction, being non-conserved, is very likely to also be junk.
A DNA scan of all bacteria/virus from patients with infections would be boon to public health. I can think of two good reasons it should be free to do DNA scans on every patient with an infection. Tabulating the data to watch for the spread of a desease. Studying the changes in bacteria/virus DNA as they develop resistances to treatments. I can also think of three good ways to pay for it. The government wanting to control desease outbreaks. Researchers wanting data for research. Pharmaceutical companies wanting data to make drugs to sell.
Having to work for a living is the root of all evil.
Well, yeah, and the appendix was also a junk organ until quite recently. Just because we don't know what it does doesn't mean it is non-functional.
It's nice that the price of using DNA sequencing technology is coming down, but I have a question:
So what?
Doctors aren't trained to use DNA sequencing equipment. And even if they were, how many disorders can be diagnosed by gene sequencing? Other than confirmation of genetically carried disorders, gene sequencing would never even be able to help diagnose anything.
I do not fail; I succeed at finding out what does not work.
Actually we have an "old" Illumina (same manufacturer) and get bulk discounts on the consumables so a dedicated lab running the machine day and night might still be a better ROI.
Actually, probably the best use of these machines will be to sequence tumor DNA to determine the best treatment option.
For example, is your melanoma response to RAF inhibitors?
Such work is going on at the NIH NGS paper (PDF) and, in this case, the more data to correlate responses with, the better.
Of course, not really something for your average doctor.
Well, the trick to getting a fat cancer research grant (FCRG) is that you have to be able to contort your pet project into something that somehow conveniently plays into the hands of human cancer research. Photosynthesis might be a bit too far off, but I'm sure you could get good bucks for studying root nodules or the effects of unengineered agrobacterium. Then again, one of the labs I worked in as an undergrad studied the neurodevelopment of C. elegans under a FCRG, so perhaps I'm being too stringent in my definition of contortability.
Bio questions? Ask me to start a Q&A journal. Computer analogies available for most topics!
Nah, it's less exciting than that. We're pretty sure that most of the non-functional DNA has no purpose other than functioning as spacer material. When a chromosome is functioning normally in a cell, it forms a roughly spherical shape comprised of many loops that go out toward the edge and then back in toward the middle. The outermost parts of these loops are the starting positions of very important genes, which makes them more accessible to the proteins that are supposed to make use of them. The non-functional DNA provides enough flex room to let the chromosome get bent like this. The bends themselves are accomplished by proteins called histones. One of the ways in which the cell can effect gene regulation is by changing how far out a particular gene's promoter region is.
For this DNA, the important thing about it is that we know the sequence does not matter (or, at least, matters very little.) The repetitive elements that comprise this DNA may provide a gripping point (like handles in a rock climbing gym) but they're not really important themselves. Since humans are so complex and we're so good at finding and storing food, the cell has every motivation to find little tricks like this to streamline these complex processes. Bacteria, by contrast, have absolutely no ability to support the stress caused by chromatin remodelling, and the gaps between genes are typically less than a thousand nucleotides.
That being said, on occasion some of the dead and inactive DNA rises to the challenge and becomes useful. One of the most prodigious components of the non-functional human genome are the corpses of retroviruses that integrated their payloads with us and then became inactive due to mutation. We've co-opted these genes on a few occasions, including once to anchor the placenta to the uterine lining during pregnancy, an adaptation that allows higher mammals to support much larger fetuses. (For comparison, mice lack this.) The cervical plug that forms during pregnancy to protect the fetus from the exterior environment is also comprised predominantly of malformed and misshapen bits of random viral capsid (shell) proteins.
A lot of people assume the genome has to be this nice, neat, clear-cut thing, and get indignant at the shortsightedness of scientists who seem to be arrogant about what is important and what isn't. The truth is that we know a lot more now, and the genome is really more like a giant vibrating box of LEGO bricks that sometimes assembles random bits of useful stuff out of itself.
Bio questions? Ask me to start a Q&A journal. Computer analogies available for most topics!
...then again, you probably already knew half of that. It is such a pain to keep track of who knows what in this place!
Bio questions? Ask me to start a Q&A journal. Computer analogies available for most topics!
Au contraire; that tactic doesn't exactly yield a coherent supply of intelligent conversation.
Bio questions? Ask me to start a Q&A journal. Computer analogies available for most topics!
Well, gee. I guess my wife must be one of the above, then, huh?
How about:
- researchers looking for causes/cures for diabetes.
- researchers looking for causes/cures for cancer.
- researchers looking for causes/cures for stupidity.
Besides, you double-posted. "Insurance companies" and "crooks" are synonymous. :P
"City hall" in German is "Rathaus" Kinda explains a few things......
In summary, the current figures we have are that two-thirds of the genome is known to be junk, less than 9% is known to be functional, and almost all the remaining fraction, being non-conserved, is very likely to also be junk.
Please frame this and hang on the wall so you can laugh at yourself in 20 years when all of this is proven to be laughably ignorant.
How do you know a piece of DNA isn't being used? Maybe because every time you've created an mRNA library, you never seem to see these sequences expressed? Well, how do you know that the DNA in question isn't activated by some obscure environmental conditions, or other specific conditions which are never seen in your laboratory? How can you really prove that this sequence of DNA is not activated ANYWHERE, EVER, AT ALL? You CAN'T know that, using today's science, because we simply don't understand enough about genetics to really say with certainty that a specific DNA sequence is NEVER expressed.
Hehe, yes well, it was a good explanation.
I guess I just don't like the idea of unequivocally claiming that we know exactly how something works. It's just backfired so many times in the history of science. There was a rather famous exchange during the 1970s between Bob Abeles (the guy who worked out the mechanisms of vitamin B12 mediated reactions) and some Harvard chemists who said the chemistry he was proposing was "impossible." Well, long story short, Abeles was right and the Harvard consortium was wrong.
Please read the grandparent post properly. We do know that dead transposons and viruses don't do anything, and even when they were active (long ago), they functioned as autonomous, selfish genetic elements. The impact that these elements had on the host organism was invariably deleterious, just as with active viruses that infect us today.
Please learn more about genetics before pontificating in future. I suggest starting by reading about transposable elements.
If you want certainty, look to mathematics, not science.
I know many slashdotters look down on biologists and biology, but believe it or not we actually have examined the questions you are asking.
Over half the human genome is made up of dead transposable elements and viruses. When these genetic elements were active, they spent many generations expanding through the genome by repeatedly inserting many thousands of copies of themselves throughout the genome. For example, there are around 500,000 LINES and 1,500,000 SINES, almost all of which are long dead (i.e. inactive), and which together make up over a quarter of the human genome. They are no longer being conserved; they have no plausible function; Occam's Razor suggests they are exactly what they appear to be: foreign nucleic acid that invaded the genome for its own purposes.
Glad I could help. :)
Bio questions? Ask me to start a Q&A journal. Computer analogies available for most topics!