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New Method To Revolutionize DNA Sequencing
Posted by
ScuttleMonkey
on Mon Jan 05, 2009 01:22 PM
from the start-saving-up-to-buy-a-clone dept.
from the start-saving-up-to-buy-a-clone dept.
An anonymous reader writes "A new method of DNA sequencing published this week in Science identifies incorporation of single bases by fluorescence. This has been shown to increase read lengths from 20 bases (454 sequencing) to >4000 bases, with a 99.3% accuracy. Single molecule reading can reduce costs and increase the rate at which reads can be performed. 'So far, the team has built a chip housing 3000 ZMWs [waveguides], which the company hopes will hit the market in 2010. By 2013, it aims to squeeze a million ZMWs [waveguides] onto a single chip and observe DNA being assembled in each simultaneously. Company founder Stephen Turner estimates that such a chip would be able to sequence an entire human genome in under half an hour to 99.999 per cent accuracy for under $1000.'"
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Submission: New method to revolutionise DNA sequencing by Anonymous Coward
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Hardware: Robot Makes Scientific Discovery (Mostly) On Its Own 250 comments
Hugh Pickens writes "A science-savvy robot called Adam has successfully developed and tested its first scientific hypothesis, discovering that certain genes in baker's yeast code for specific enzymes which encourage biochemical reactions in yeast, then ran an experiment with its lab hardware to test its predictions, and analyzed the results, all without human intervention. Adam was equipped with a database on genes that are known to be present in bacteria, mice and people, so it knew roughly where it should search in the genetic material for the lysine gene in baker's yeast, Saccharomyces cerevisiae. Ross King, a computer scientist and biologist at Aberystwyth University, first created a computer that could generate hypotheses and perform experiments five years ago. 'This is one of the first systems to get [artificial intelligence] to try and control laboratory automation,' King says. '[Current robots] tend to do one thing or a sequence of things. The complexity of Adam is that it has cycles.' Adam has cost roughly $1 million to develop and the software that drives Adam's thought process sits on three computers, allowing Adam to investigate a thousand experiments a day and still keep track of all the results better than humans can. King's group has also created another robot scientist called Eve dedicated to screening chemical compounds for new pharmaceutical drugs that could combat diseases such as malaria.
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99.3% accurate? (Score:5, Insightful)
That's, what, 28 incorrect base pairs out of 4000? I'm not a biologist, but is this considered an acceptable error rate? Even the hopes of 99.999% accuracy seems really awful when there are about 3 billion base pairs in a human genome.
I realize that we aren't going to be trying to make a cloned copy from this data, but what uses is this "good enough" for?
Re:99.3% accurate? (Score:5, Insightful)
I realize that we aren't going to be trying to make a cloned copy from this data...
What makes you so sure? Who knows where this will lead?
Parent
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Sorry, you're asking for the impossible - I've never seen a well-organized mammoth hunt.
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Re:99.3% accurate? (Score:4, Funny)
Oh well. At least it's not the first time somebody missed a point on /.
Don't you mean "Oh well. At least it's not the first time somebody missed a point on /".
Parent
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It's not too bad. I don't think the human version of the polymerase has a better error rate. However, while being in a biological entity, DNA replication also has other integrity checks.
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That's, what, 28 incorrect base pairs out of 4000? I'm not a biologist, but is this considered an acceptable error rate? Even the hopes of 99.999% accuracy seems really awful when there are about 3 billion base pairs in a human genome.
I realize that we aren't going to be trying to make a cloned copy from this data, but what uses is this "good enough" for?
More than good enough for forensic work at least, I'd wager.
Re:99.3% accurate? (Score:5, Interesting)
Parent
Re:99.3% accurate? (Score:5, Informative)
Parent
Re:99.3% accurate? (Score:4, Informative)
It's common practice in bioinformatics to measure the same data repetitively in an effort to reduce the error. While 0.993 isn't very good, (0.993)^3 is pretty awsome. In practice, the errors might be correlated (as in a flaw in the measuring system), so the benefit of re-measuring might not be exponential...however it should be darn close.
Parent
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If you got B on the second run you'd be pretty sure it was incorrect.. ;-)
Re:99.3% accurate? (Score:5, Insightful)
There is a saying from the old sailing days. "Never set sail with two compasses". One is ok, three is better. But never two. The paralysis from not knowing which is right is far worse than being wrong and correcting later.
Parent
Re:99.3% accurate? (Score:4, Funny)
Unless of course all three of your compasses are giving you different readings. In that case, you simply yell "Where the hell is my sextant."
Parent
Re:99.3% accurate? (Score:5, Funny)
If you were sequencing DNA and got a B then you'd seriously need to recheck the equipment (or the competence of the operator). Perhaps a T or a G, or even a C but never a B.
Parent
Re: (Score:3, Interesting)
This assumes that the method simply has a random chance of getting each data point wrong. What if it is something systematic with the method that causes it to read one gene wrong? In other words, it reads the gene as a 'T' every time despite it really being an 'A'. No matter how many tests you run, it will still result in a wrong answer.
nitpick (Score:3, Informative)
One base-pair does not a gene make.
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One base-pair does not a gene make.
But a one base-pair change can unmake the gene pretty well.
Tons of major debilitating mutations are due to a point mutation.
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Given the expense of doing an entire genome, alternative is a 25% accuracy rate. What 99.3% does is let you do a bulk scan looking for interesting areas. Prospecting. Now you can adjust therapies the match likely genome sequences. "Ah Ms. X, I see you likely have gene XYZ. Medication A, B, and C won't work for you so let's try D."
In other words, you don't need perfect results to now bias the odds in you favor.
Re:99.3% accurate? (Score:5, Insightful)
If they can sequence the whole thing in less than 30 minutes one time with a 0.001% "read" error rate, my guess is that they can get it probabilistically near 100% correct in 2 hours or so.
By the way, what's the current error rate? Is it 0? (just asking)
Parent
Re:99.3% accurate? (Score:5, Interesting)
Or you could run a parallel processing setup, 3-5 sequencing chips all given the same sample at the same time. More expensive, but you'd get that effective 100% rate in the half hour time.
$5k for a genetic sequencer that could give effectively 100% accuracy in half an hour would be pittance for pretty much every hospital in the US.
Hell, the first malpractice lawsuit it prevents (detect a disorder that would make a commonly used treatment crippling or fatal to the patient) would pay for the machine 1000 times over.
Parent
Re:99.3% accurate? (Score:5, Funny)
1 Hour Genome Sequencing: 30,000 errors or less or YOUR MONEY BACK!
Parent
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Do it several times over with different cells and "vote" on the inconsistencies between trials. If 5 out of 7 copies of the DNA look like the base at position X is tyrosine, then it's most likely that it's tyrosine.
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I suppose that running it twice or trice will increase the accuracy a lot more.
Which makes it still blazing fast.
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When I have sequences done the conventional way, I get less than 1000 base pair reads back. Generally 2 or 3 are ambiguous enough that the machine reads them incorrectly or not at all. 28 out of 4000 is the same as 7 out of 1000, so this is roughly the same magnitude of error. Less accurate than what we use now, but more economical to do really large sequences.
I don't know how the method works (site is slashdotted anyone got a DOI for the paper?) so it's hard to tell whether repeating the reads would
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Re: mistakes and inaccuracies...
You run two or three trials and do "a check sum" ...a la Raid inter leafing...errors stand out and are discarded..
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That's, what, 28 incorrect base pairs out of 4000? I'm not a biologist, but is this considered an acceptable error rate? Even the hopes of 99.999% accuracy seems really awful when there are about 3 billion base pairs in a human genome.
That's a very good question, but consider that 100% is impossible. Even the cell's own machinery, under development for millions of years, makes mistakes at a frequency that would be lethal if that's all there was.
In this case, the error rate seems in the neighborhood of rival techologies. The way to deal with it is the same way the cell uses: redundancy. Sequence segments or the whole thing more than once, the likelyhood of bases in error is significantly decreased. If you run 3 sequencings, there's ev
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... and to prove that last point I just realized that I was redundant with the non-coding DNA and introns. I think. No wait, I meant to do that, this way if you misread "introns" it will still be covered by the "non-coding DNA" bit. And that's the last biochemistry joke out of me today.
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There's an easy and obvious way around this - just run 3 simultaneous instances and error-check by consensus. Still able to run the whole thing in under a half hour and still pretty cheap at ~$3000.
Sub-$1000 genome sequencing (Score:4, Funny)
Sub-$1000 genome sequencing will put the creation of 'designer' kids into the realm of the affordable for much of the middle class. Scary stuff. Now we just need to combine that with cheap and reliable cloning techniques and my plans for world domination will be comlete!
Re:Sub-$1000 genome sequencing (Score:4, Funny)
Hopefully you'll fix that nasty intercalary deletion [wikipedia.org] bug first!
Parent
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I will, but I gotta P first!
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Hopefully you'll fix that nasty intercalary deletion bug first!
As long as it's not a missing G, T, C, or A, he'll be OK.
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Sorry, it comes to my attention that you are missing a 'p' in the word 'complete', without a 'p', the world is never completed.
P, as in...I think you will figure that out by checking the spam.
Real-Time DNA Sequencing from Single Polymerase Mo (Score:2, Informative)
Abstract:
Kicks ass on Moore's Law... (Score:5, Insightful)
I think this qualifies as a true 'technological singularity' [wired.com]
error correction (Score:3, Insightful)
Something like the error correction on an audio compact disk ?
Re:error correction (Score:5, Insightful)
Yes. It's called "natural selection". :P
Parent
Article in Science (Score:2, Informative)
I assume that the hardware at Science can withstand a slashdotting better than the crappy blog linked in the summary:
http://www.sciencemag.org/cgi/content/abstract/323/5910/133 [sciencemag.org]
I guess I can drop my X prize plans (Score:3, Informative)
Slashdotted: Abstract and Fulltext (Score:3, Informative)
Grammar ambiguity (Score:3, Interesting)
Company founder Stephen Turner estimates that such a chip would be able to sequence an entire human genome in under half an hour to 99.999 per cent accuracy for under $1000
Does that mean that the chip costs $1000 or that each human genome processed costs $1000?
New Scientist Write Up (Score:3, Informative)
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Using 454 sequencing you get average read lenghts of ~400-500 bp
I suspect someone had confused 454 with the other popular next-gen sequencing technique from Illumina, which does give very short reads.
Read lenghts around 20 bp would be pretty much useless. At least for de novo sequencing..
Not necessarily. If you can drive the cost/base down far enough, you can make short reads worthwhile if you use a shotgun approach and try for large-scale coverage. Especially if you can produce the short reads at a lower rate of time/base.
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The use of short reads for de novo assembly only makes sense if you want a rough draft of a genome, not the complete thing. There are way too many transposable elements, repeats, variation, etc. to accurately reconstruct even a bacterial genome with short reads. Nowadays, people don't even bother trying to piece it all together. They get down to a few dozen large fragments and say "good enough". It just costs too much to get the last 1-2% with a random sequencing approach.
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Gattaca was supposed to show us a dark future. It was supposed to be a cautionary tale. The message was, "if your DNA isn't good enough, you'll have to make do banging Uma Thermon - poor you."
I don't think the producers thought their cunning plan all the way through.
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Although humans differ from one another in about 0.1% base pairs for a total of 3 million, the number of difference that describe human variability may be vastly smaller than this. First you discard non-coding DNA which gets you done to 30,000.
Except that when our differences are so small, the non-coding regions are even more important. They control what genes are active and to what degree. That's nearly as important as the genes themselves.
Genes are only part of the puzzle. You need to know what to do with them, and non-coding regions provide some of that along with the cellular machinery.
Scientists used to call them "junk" DNA where junk == "I can't figure it out". Why would cells spend all that energy maintaining something useless? Not very li
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error's
That character you're using... I don't think it means what you think it means...
You must be new here. You see, here on teh interweb, many of us are terribly afraid of word's ending in "s" - Plural's, possessive's, contraction's with the word "is", and occasionally even name's. The apostrophe is a polite way of warning the general reading public that an "s" is approaching so that we can brace ourselve's accordingly.