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New Method To Revolutionize DNA Sequencing

ScuttleMonkey posted more than 5 years ago | from the start-saving-up-to-buy-a-clone dept.

Biotech 239

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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Gattica... (1, Funny)

Anonymous Coward | more than 5 years ago | (#26332631)

Gattica, here we come!

But at least there's Uma Thurman.

Re:Gattica... (0)

Anonymous Coward | more than 5 years ago | (#26332687)

Lets see your genetics save you from my Hanzo sword.

Re:Gattica... (1)

CorporateSuit (1319461) | more than 5 years ago | (#26333363)

but...

We have Uma Thurman NOW...

Re:Gattica... (1)

chill (34294) | more than 5 years ago | (#26333553)

Unless we perfect cloning, there are going to be a few billion people who find little consolation in that.

+digg (-1, Offtopic)

Anonymous Coward | more than 5 years ago | (#26332657)

+digg, cool story bro

Re:+digg (0)

Anonymous Coward | more than 5 years ago | (#26333271)

[citation needed]

99.3% accurate? (4, Insightful)

Valdrax (32670) | more than 5 years ago | (#26332679)

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? (4, Insightful)

imamac (1083405) | more than 5 years ago | (#26332727)

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?

Re:99.3% accurate? (1, Funny)

nbauman (624611) | more than 5 years ago | (#26332841)

I want a cute little baby velociraptor!

Re:99.3% accurate? (1)

bigattichouse (527527) | more than 5 years ago | (#26332951)

I want mammoth burgers, the original human food. oh, and organized mammoth hunts on the canadian tundra.

Re:99.3% accurate? (2, Funny)

Rayban (13436) | more than 5 years ago | (#26333057)

Sorry, you're asking for the impossible - I've never seen a well-organized mammoth hunt.

Re:99.3% accurate? (1)

Mordstrom (1285984) | more than 5 years ago | (#26333349)

Perhaps the Borean Tundra...

Re:99.3% accurate? (2, Funny)

jd (1658) | more than 5 years ago | (#26333841)

That's because Mammoths have no opposable thumbs and therefore no means of becoming organized.

Re:99.3% accurate? (1)

0prime (792333) | more than 5 years ago | (#26333093)

Besides the current near impossibility of building a clone instead of using existing DNA, he made that statement because the method for sequencing is only 99.3% accurate. So basically, you completely missed his point, since he was saying he understood they may not need 100% accuracy (not cloning), but wondered where something with a 99.3% sequencing accuracy would be applicable.

Re:99.3% accurate? (1)

imamac (1083405) | more than 5 years ago | (#26333131)

Oh well. At least it's not the first time somebody missed a point on /.

Re:99.3% accurate? (3, Funny)

fracai (796392) | more than 5 years ago | (#26333423)

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 /".

Re:99.3% accurate? (1)

the_humeister (922869) | more than 5 years ago | (#26332749)

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.

Re:99.3% accurate? (0)

Anonymous Coward | more than 5 years ago | (#26332751)

Coverage

Re:99.3% accurate? (2, Insightful)

aoeusnth (101740) | more than 5 years ago | (#26332787)

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? (1)

Tubal-Cain (1289912) | more than 5 years ago | (#26333153)

At the very least, this method can be a cheap way to acquit suspects. Those that come up positive can ask for the more accurate test.

Re:99.3% accurate? (1)

ogdenk (712300) | more than 5 years ago | (#26333715)

Could also be useful the other way around.

1.) Rapidly sequence a suspect's DNA

2.) Find a cheap way to make "good enough" copies

3.) Plant evidence

4.) ????????

5.) PROFIT!!!!

Re:99.3% accurate? (4, Interesting)

Maximum Prophet (716608) | more than 5 years ago | (#26332789)

How many errors are introduced during normal human reproduction? The dogs they've cloned so far are less than 99.999% identical.

Re:99.3% accurate? (4, Informative)

peter303 (12292) | more than 5 years ago | (#26333547)

One in 10E8 is the DNA base-pair copy error rate. Even so thats around 60 when a sperm meets egg. Another much more when there a trillion somatic cells dividing on average 50 times each in a human lifetime. The vast majority are errors are neutral, but accumulating ten or so specifically unluckly ones in a cell may be a cancer.

Re:99.3% accurate? (4, Informative)

Anonymous Coward | more than 5 years ago | (#26332813)

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.

Re:99.3% accurate? (1)

liquidpele (663430) | more than 5 years ago | (#26332973)

That formula isn't quite accurate.. lets say the first sequencing you got A and in the second you get B. You don't know which one was the error, so you'd have to test enough times that you felt confident about what the real value was. A minimum of 3 tests would be necessary to even be fairly sure about the result, but more than that would be needed to have really high accuracy.

Re:99.3% accurate? (2, Funny)

evilNomad (807119) | more than 5 years ago | (#26333045)

If you got B on the second run you'd be pretty sure it was incorrect.. ;-)

Re:99.3% accurate? (1)

wealthychef (584778) | more than 5 years ago | (#26333881)

The point is, which pieces are incorrect? It's highly likely to be slightly incorrect, but you want it to be highly likely to be completely correct.

Re:99.3% accurate? (5, Insightful)

scorp1us (235526) | more than 5 years ago | (#26333061)

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.

Re:99.3% accurate? (4, Funny)

shaitand (626655) | more than 5 years ago | (#26333395)

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.

Re:99.3% accurate? (2, Interesting)

MyLongNickName (822545) | more than 5 years ago | (#26333549)

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.

Re:99.3% accurate? (2, Informative)

Anonymous Coward | more than 5 years ago | (#26333889)

If you RTFP (requires subscription), no systematic errors were detected
http://www.sciencemag.org/cgi/content/full/323/5910/133

Re:99.3% accurate? (2, Informative)

prograde (1425683) | more than 5 years ago | (#26333401)

It's common practice in bioinformatics to measure the same data repetitively in an effort to reduce the error.

It's common practice on Slashdot to read the article before posting. From the abstract of the Science article:

Consensus sequences were generated from the single-molecule reads at 15-fold coverage, showing a median accuracy of 99.3%, with no systematic error beyond fluorophore-dependent error rates.

So that's 99.3% after averaging 15 reads. Not exactly replicating the same read 15 times..more like taking random starting points and aligning the results where they overlap, so that each base is covered in 15 different reads.

Don't get me wrong - this is really cool, and a massive speed-up over current "next-gen" sequencing. And I'm sure that it will get better.

To answer the GP - yes, this is an acceptable error rate, for now.

Re:99.3% accurate? (1)

Homericus718 (1431553) | more than 5 years ago | (#26333433)

Although this repetition you speak of is important, it is far less beneficial than exponential. (0.993)^3 is actually less accurate (0.979), I would guess you meant to do (1-(1-0.993)^3) = 0.9999997. Also, re-measuring data does not give an exponential error decrease. Most signal to noise levels go up as the square root of the number of samples taken. This is assuming the error isn't systematic.

Re:99.3% accurate? (0)

Anonymous Coward | more than 5 years ago | (#26333475)

Come on moderators, whip out your calculators and check. (0.993)^3 is even worse than 0.993 in terms of accuracy.

Re:99.3% accurate? (1)

timeOday (582209) | more than 5 years ago | (#26333551)

While 0.993 isn't very good, (0.993)^3 is pretty awsome.

No, 0.993^3 is only 97.9%; how about 1-(1-0.993)^3 :)

Re:99.3% accurate? (1)

przemekklosowski (448666) | more than 5 years ago | (#26333883)

While 0.993 isn't very good, (0.993)^3 is pretty awsome.

(0.993)^3 would suck actually, resulting in 0.979---but fortunately the error rate is 1-(1-0.993)^3), i.e. a pretty awesome .9999997 (assuming independent errors and such)

Re:99.3% accurate? (1)

jbeaupre (752124) | more than 5 years ago | (#26332823)

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? (4, Insightful)

ccguy (1116865) | more than 5 years ago | (#26332825)

Well, depends if those 28/4000 errors are the same in each run or not.

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)

Re:99.3% accurate? (4, Interesting)

Adriax (746043) | more than 5 years ago | (#26333599)

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.

Re:99.3% accurate? (0)

Anonymous Coward | more than 5 years ago | (#26333887)

By the way, what's the current error rate? Is it 0? (just asking)

No: the error rate depends on the technology. First of all, in all sequencing technology, the error rate increases as the sequence gets longer. That is, the probability of an error in the first bases is much smaller than a probability of an error in the latter bases.

"Sanger sequencing", the most established method for sequencing, tends to peter out by the time it gets to about 1000bp reads. However, Sanger sequencing is slow and expensive.

Newer high throughput sequencing technologies (Illumina, Applied Biosystems) can generate much more sequence at once, but compromise in that read length is about 25-100bp, and the sequences are more prone to errors (again, especially in the latter bases). The Applied Biosystems technique has a built in error checking code, which is pretty trick.

Finally, there is a medium range solution (454) which gives ~400bp reads, at a lower throughput.

So, taking that all together, the point is that none of these are good enough to just sequence the human genome in a single shot. Instead, the standard approach is to sequence at a certain "coverage". Practically, sequencing a genome de-novo with Sanger sequencing often takes about 10x coverage (e.g. need to sequence the human genome about 10 times over) to get confidence in the final sequence. Using more high throughput sequencing methods, we need more like 20-40x coverage to get an acceptable error rate. This also has to do with assembling the reads together, but I won't get into that. Lets just say, the human genome is not a random set of bases, and has much repetitive sequence.

So, take home, no matter how you sequence, getting as high-accuracy pass of the human genome, you can generally make up quality with quantity. For the human genome, 10X coverage is 30B bases.

And, lastly, there is the effort of "resequencing", where you have a reference genome, and are simply looking for variants. For example, we are not going to sequence many people de-novo, but instead in comparison to existing sequencing to identify difference. Here, lower coverage is acceptable.

Re:99.3% accurate? (5, Funny)

morgan_greywolf (835522) | more than 5 years ago | (#26332831)

1 Hour Genome Sequencing: 30,000 errors or less or YOUR MONEY BACK!

Re:99.3% accurate? (1)

mapkinase (958129) | more than 5 years ago | (#26332845)

You can decrease the error rate by increasing coverage from 15-fold to N-fold

Re:99.3% accurate? (1)

Stile 65 (722451) | more than 5 years ago | (#26332867)

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.

Re:99.3% accurate? (1)

msh104 (620136) | more than 5 years ago | (#26332873)

I suppose that running it twice or trice will increase the accuracy a lot more.
Which makes it still blazing fast.

Re:99.3% accurate? (1)

smoker2 (750216) | more than 5 years ago | (#26333611)

Thrice. [askoxford.com]

Re:99.3% accurate? (1)

cobaltnova (1188515) | more than 5 years ago | (#26332927)

3 billion * 99.999% = 30. That's not "really awful." That's pretty darn good! If you need better results, sequence the same DNA 3 times in an hour and a half to get upwards of ten 9's accuracy (assuming the errors are uncorrelated, of course).

Re:99.3% accurate? (1)

bennomatic (691188) | more than 5 years ago | (#26333431)

Actually, you're off by a factor of 1000.

3,000,000,000 * 0.99999 = 2,999,970,000

So your error count is 30,000.

Re:99.3% accurate? (1)

Hatta (162192) | more than 5 years ago | (#26332937)

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 get you a different set of random errors or just give you the same errors over again. But I'd imagine that if you really needed extremely high accuracy, you could just have it done several times and pick the consensus sequence.

DOI was Re:99.3% accurate? (1, Informative)

Anonymous Coward | more than 5 years ago | (#26333593)

DOI: 10.1126/science.1162986

Re:99.3% accurate? (2, Insightful)

Anonymous Coward | more than 5 years ago | (#26332947)

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..

MOD UP (0)

Anonymous Coward | more than 5 years ago | (#26332957)

see title

Re:99.3% accurate? (1)

philspear (1142299) | more than 5 years ago | (#26333043)

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 even a smaller chance that you'll have an error 2 out of 3 times.

Anyway, thanks to the way the genome works, the vast VAST majority of errors won't matter as much: non-coding DNA, introns, the codons themselves have a high degree of redundancy (IE TCT codes for serine, if the last T gets read as a C accidentally, it will still give you serine.)

Granted, there are important uses the sequence itself has. Fortunately most of those themselves can be done redundantly. If you're trying to run an in-situ hybridization for a sequence and your probe has one or two errors in it, my understanding is that would mess up the in-situ, but people often use more than one probe.

I should point out I'm not a biochemist, so take everything with a grain of salt. As with everything, I am definitely not error free.

Re:99.3% accurate? (1)

philspear (1142299) | more than 5 years ago | (#26333095)

... 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.

Re:99.3% accurate? (1)

thesandtiger (819476) | more than 5 years ago | (#26333111)

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.

Re:99.3% accurate? (1)

untermensch (227534) | more than 5 years ago | (#26333235)

The idea is to sequence each portion of the genome many times over. With enough redundancy you can detect these errors, so your final annotated copy would have a much higher accuracy.

Re:99.3% accurate? (1)

fuzzyfuzzyfungus (1223518) | more than 5 years ago | (#26333411)

I suspect, given that this system is fast, massively parallel, and not terribly accurate, that (should it reach production use) its users will end up relying on multiple runs and clever error correction techniques. As long as the .7% errors are random rather than systematic, you should be able to reduce the effective error rate by using "best x out of y", with X and Y chosen for your budget and risk tolerance.

It probably also will find a niche, in spite of its error rate; because there is just so damn much DNA that biologists would like to sequence. Millions of known species, loads more unknown, even just grabbing a sample of the environment and sequencing whatever is inside [wikipedia.org] which can turn up loads of stuff we didn't even know was there. I strongly suspect that there are large numbers of situations where an approximation that we can afford is far more valuable than a fully accurate sequence that we can't.

Re:99.3% accurate? (1)

cat_jesus (525334) | more than 5 years ago | (#26333441)

Do the sequencing three times. So you spend 1.5 hours instead of .5 hours. If you're really worried do it 7 times. That should be enough to weed out the errors.

Re:99.3% accurate? (1)

marcosdumay (620877) | more than 5 years ago | (#26333487)

So, instead of $1000, you must spend $3000 and get the same result in one hour that we needed 10 years and several millions to get at the 90's... I see, that is useless.

Re:99.3% accurate? (1, Informative)

Anonymous Coward | more than 5 years ago | (#26333779)

It's super fine! It's very very good. I think there is some confusion since they are using different metrics for accuracy. The 99.3% accuracy likely does mean an expected 28 errors per read of 4000 base pairs. But their 99.999% accuracy likely means that there's 99.999% confidence that there are no errors at all. Here's a crash course in DNA sequencing with hand waving and generalization. You slice the DNA into (mostly) random bits. With old methods they were about 20 BP long. With newer 454 pyrosequencing I think they were 100 BP long, or longer. This new technique uses about 4000 long fragments. Then you use some kind of magic to look at those slices. Pyrosequencing gets its name because you have reagents involving pyrophosphate, that attach to your base pairs. So one at a time you can add reagents to combine with the chain, and when the pyrophospate is released it glows. The brighter, the more of the same BP in a row there was. So you put them all on a slide and can do thousands at once. Mix reagents, your CCD looks for glows. Neato! Haven't read this article to see how it works but it doesn't really matter how, so long as it does work.

But, what do you do with these nice little fragments? (not so little if they're doing 4000 long reads!) Well, you run a pattern matching algorithm to line them up! You are right you'll have 28 errors on average per fragment. But, with 4000 long fragments, if you have overlap of say 1000, even with all 56 errors occurring in that overlap (bad luck) I think you'll find that the odds of this being the correct matching, with 56 errors, are massively massively higher than the odds of the other 944 base pairs matching by random chance or read errors! So these errors won't disrupt the assembly, at least it would be amazing if they actually did. Now typically one would use 15 fold overlap. That is, you run enough fragments so that, statistically speaking, you have high confidence that every basepair will be a member of at least 15 different fragments. So, after assembling, even with some assembly errors, you can do majority voting. If at least 9 out of those 15 (you could in fact use 8 but I'm leaving 1 extra!) all agree, then that's the base pair that goes there!

Now that that's "explained," what are the actual odds of an error in a genome of length 3*10^9? Well, lets imagine we have the whole human genome done in this way, with reads of length 4000, and with 99.3% accuracy for any given base pair. Well, then in our assembled genome, the odds of an error at a given basepair will be (0.993)^14 * (0.007), odds of two, thee, also calculable. However, when assembling, because the reads are so long, you can be extremely confident that that is where they go, so one error won't disrupt you at all. Even 6 is fine, because the other 9 fragments that overlapped that BP all agree still. The odds of 7 or more errors on the same basepair is something like 10^(-15). The probability of having this occur ZERO times out of 3 billion base pairs is 99.9997%. So that's where their number comes from. It's not that out of these 3 billion base pairs, 99.9997% are right, meaning an expected OVER 9000 base pairs will be wrong. It's saying that with 99.9997% confidence, there are ZERO errors. If there is an error, there's again many 9s chance that it's only a single error. That's pretty damn good! Nearly a 1 in a million chance of even a single error! Of course, the errors won't be uniform, and it may be position dependent (pyrosequencing sure is, I don't know about this technique though). And the coverage won't be uniform, either, so a BP that already has a higher than average proportion of errors could, by bad luck, end up with a low amount of coverage to boot! But I'm sure if you double your coverage for an extra $1000 you can be super sure of the coverage, and can also afford to be extra pessimistic in your error rates, and still get your 99.9999% chance of an error-free sequence.

Re:99.3% accurate? (0)

Anonymous Coward | more than 5 years ago | (#26333809)

from the science article:

"Consensus sequences were generated from the single-molecule reads at 15-fold coverage, showing a median accuracy of 99.3%, with no systematic error beyond fluorophore-dependent error rates."

The method basically relies on not getting an accidental fluorophore to float into the reading frame, which happens about .7% of the time. This is a random event and non-systematic. Taking twice as long being exponentially more accurate

Re:99.3% accurate? (0)

Anonymous Coward | more than 5 years ago | (#26333817)

Run it a few times over the same sequence, and then take the most popular results. If the errors are generated randomly(I don't actually have any reason at all to believe this is the case), rather than something systematic in the process, the chances of a collision of false reads is pretty small. If it only takes 1/2 an hour to run, so if it was required more samples wouldn't cost that much(compared to something like artificially creating an organism).

It will probably be good enough for forensic work and most biological stuff. Our current methods are pretty far from perfect.

Re:99.3% accurate? (1)

wealthychef (584778) | more than 5 years ago | (#26333857)

You can repeat the analysis several times to increase accuracy, I would think. Do the analysis 3 times and it might increase to 99.9999997%, for example.

Er (0)

Anonymous Coward | more than 5 years ago | (#26332695)

You don't want to jump from 150 to 3 billion bases. Read up on shotgun sequencing. The mere fact that a given chunk is 150 bases is immaterial, though of course if you could lengthen that by a factor of five or ten it would improve accuracy and reduce computation on assembling the whole thing.

99.999% accuracy (0)

BigGar' (411008) | more than 5 years ago | (#26332699)

Headline you'll never see: Have your genome sequenced while you wait. No more than 30,000 error's or your money back!!!

Re:99.999% accuracy (0, Offtopic)

H0p313ss (811249) | more than 5 years ago | (#26332881)

error's

That character you're using... I don't think it means what you think it means...

Re:99.999% accuracy (0)

Anonymous Coward | more than 5 years ago | (#26333129)

yes, yes, I was in a hurry and didn't proofread me preview.

Re:99.999% accuracy (1)

troll8901 (1397145) | more than 5 years ago | (#26332979)

... slowly leading to an era where helicopters can transform into airplanes, blood sampling is completely painless, brain contents can be downloaded by scanning the eyes, and clones can be produced in an afternoon.

Enter Arnold Schwarzenegger's clone, Adam Gibson [wikipedia.org] !

Sub-$1000 genome sequencing (4, Funny)

morgan_greywolf (835522) | more than 5 years ago | (#26332713)

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 (3, Funny)

Ethanol-fueled (1125189) | more than 5 years ago | (#26332909)

"...my plans for world domination will be comlete!"

Hopefully you'll fix that nasty intercalary deletion [wikipedia.org] bug first!

Re:Sub-$1000 genome sequencing (2, Funny)

morgan_greywolf (835522) | more than 5 years ago | (#26333071)

I will, but I gotta P first!

Re:Sub-$1000 genome sequencing (2, Funny)

CorporateSuit (1319461) | more than 5 years ago | (#26333535)

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.

Re:Sub-$1000 genome sequencing (1)

sam0737 (648914) | more than 5 years ago | (#26332911)

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 (2, Informative)

mapkinase (958129) | more than 5 years ago | (#26332805)

Abstract:

We present single-molecule, real-time sequencing data obtained from a DNA polymerase performing uninterrupted template-directed synthesis using four distinguishable fluorescently labeled deoxyribonucleoside triphosphates (dNTPs). We detected the temporal order of their enzymatic incorporation into a growing DNA strand with zero-mode waveguide nanostructure arrays, which provide optical observation volume confinement and enable parallel, simultaneous detection of thousands of single-molecule sequencing reactions. Conjugation of fluorophores to the terminal phosphate moiety of the dNTPs allows continuous observation of DNA synthesis over thousands of bases without steric hindrance. The data report directly on polymerase dynamics, revealing distinct polymerization states and pause sites corresponding to DNA secondary structure. Sequence data were aligned with the known reference sequence to assay biophysical parameters of polymerization for each template position. Consensus sequences were generated from the single-molecule reads at 15-fold coverage, showing a median accuracy of 99.3%, with no systematic error beyond fluorophore-dependent error rates.

Kicks ass on Moore's Law... (4, Insightful)

djupedal (584558) | more than 5 years ago | (#26332809)

> 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.

I think this qualifies as a true 'technological singularity' [wired.com] :)

piggy backs on Moore's Law (1)

peter303 (12292) | more than 5 years ago | (#26333781)

Shotgun sequencing depends heavily on supercomputer. Thats a thousand-fold every 15 years right there. Multiply that by more intelligent software, understanding of genetics, and sequencing hardware, you may be squaring that rate.

error correction (2, Insightful)

bugs2squash (1132591) | more than 5 years ago | (#26332859)

Is there not some form of error-correction in the sequence itself that could be exploited ?

Something like the error correction on an audio compact disk ?

Re:error correction (5, Insightful)

Hurricane78 (562437) | more than 5 years ago | (#26333151)

Yes. It's called "natural selection". :P

Re:error correction (0)

Anonymous Coward | more than 5 years ago | (#26333277)

Well, the "error correction" on genes is somewhat contrary to the whole concept of evolution via mutation. Sure, there can be variation via reproduction, but if there were no mutations then the gene pool would remain stagnant.

As it is, "error correction" occurs when non-viable offspring is produced.

slashdotted! (0)

Anonymous Coward | more than 5 years ago | (#26332875)

can't slashdot automatically mirror links created in articles? that way they are always readable... slashdotted links are annoying...

current read lengths... a small erratum (0)

Anonymous Coward | more than 5 years ago | (#26332955)

Several "next generation" sequencing methods currently produce short sequences, or "tags". 454 sequencing isn't one of them - 454's typical read length is a few hundreds.

Bad summary (1)

PeterPlan (1304775) | more than 5 years ago | (#26333013)

Using 454 sequencing you get average read lenghts of ~400-500 bp. Read lenghts around 20 bp would be pretty much useless. At least for de novo sequencing..

Re:Bad summary (2, Insightful)

damn_registrars (1103043) | more than 5 years ago | (#26333393)

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.

Re:Bad summary (2, Insightful)

nodrogluap (165820) | more than 5 years ago | (#26333863)

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.

Re:Bad summary (1)

rnaiguy (1304181) | more than 5 years ago | (#26333491)

The Solexa sequencing platform has been VERY useful (admittedly not so much for de novo sequencing), with a read length of ~30 or less.

By Neruos (0)

Anonymous Coward | more than 5 years ago | (#26333113)

Fact: .01% is enough to cause mutation.

GATTACA is here (1)

arbies (1222718) | more than 5 years ago | (#26333159)

Does anyone remember the movie, "GATTACA"?

Re:GATTACA is here (2, Funny)

oni (41625) | more than 5 years ago | (#26333649)

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.

GATTACA here we come! (1)

greg_barton (5551) | more than 5 years ago | (#26333181)

1/2 hour for $1000, eh? And in another 5-10 years we'll cut that in half or more, both time and cost. It looks like the instant gene sequencing tech from GATTACA will be with us in most of our lifetimes. But even with this announced breakthough it'll be functionally the same.

maybe 60 to 1000 are significant? (1)

peter303 (12292) | more than 5 years ago | (#26333675)

Forensic genetic identification currently uses about 60 important genetic markers. Thats good enough to convict in a court law since the the chance of a duplicate may be less than a billion to one depending on marker combination.

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.

Battle Tactics :) (0, Offtopic)

headkase (533448) | more than 5 years ago | (#26333189)

Reminds me of that "Lost in Space" or whatever it was called remake. Terrible movie but remember the scene where they are fighting the spider-things and they slap down a chunk of one onto a machine which pretty much instantly reconstructs the full organism and then goes on to suggest ways to fight it based on how its built? Yeah, this could lead to one of those machines being reality.

Re:Battle Tactics :) (2, Insightful)

timeOday (582209) | more than 5 years ago | (#26333795)

This is entirely reasonable and desirable if you replace "spider-thing" with "cancer" or "aids," or even "common cold." Gene sequencing your disease and taking the right medicine for what you *actually* have - instead of today's educated guesswork - will be a HUGE advance. Thousands die every year because they have to guess a year in advance which flu strains will be prevalent and usually guess wrong.

I guess I can drop my X prize plans (2, Informative)

damn_registrars (1103043) | more than 5 years ago | (#26333197)

Since this technique should be a shoe-in for the Archon X Prize [xprize.org] .

Old News (0)

Anonymous Coward | more than 5 years ago | (#26333293)

I work in this field (our lab has 2 Illumina sequencers) and unfortunately the article is slashdotted. The single molecule stuff the summary seems to be talking about is from Pacific Biosciences (with a few hundred/thousand pools). These guys are well funded - their backers include Kliner Perkins Caufield and Byers [sp?] (a historic VC firm) and I'm hearing stories how they're turning down offers for more funding. They're probably going to be the first of the 3rd generation sequencing technologies. Next-gen sequencing has been in the news a lot lately - if you have access, check out some of the recent sequencing papers in Nature and Science. In any case, there are quite a few competing technologies. There seems to be a lot of talk about different error rates, but in reality the error introduced in the sequencing really depends on the technology. 454 aims for longer reads at the cost of fewer reads - the data I've seen gives a few hundred thousand 250-350 base reads per run of the machine. The Illumina sequencer we use gives us short 36(now longer) base reads, but we get 60 million of them. There are also other technologies which use similar fluorescence like the SOLiD system and the open-source Polonator developed in George Church's lab. All these 454, Illumina, AB SOLiD, etc have been out for at least 18 months now.

ForeSight.Org Down (1)

phantomcircuit (938963) | more than 5 years ago | (#26333483)

I guess they didn't have the foresight [foresight.org] to use a real host.

I'll be here all night folks try the steak.

not for cloning, but therapy (1)

planckscale (579258) | more than 5 years ago | (#26333559)

I believe the true benefit of this technology will not be for cloning, but for general medicine. For example, you would go to the doctor with a lump, and instead of him doing a biopsy, find cancer, chemo, invasive surgery etc etc, they first take your DNA, sequence it and then take the biopsy and identify the origin of the cancer (is the lump actually metastasized from your pancreas?). Then work on resolving the cure just based on your genetic makeup, rather than a shotgun approach. Additionally medicines for genetic problems, and a number of other diseases would be custom-tailored for your genetic makeup. If you are prone to hypertension, your DNA sequence could prove if you carry the genes for that malady. Really what this is about is a revolution in medicine. It's a private company now that is snatching up all the biggest heads in silicon valley - if and when this goes public, it could be an amazing investment.

Slashdotted: Abstract and Fulltext (2, Informative)

chihowa (366380) | more than 5 years ago | (#26333585)

It looks to be inaccessible. Here are the abstract [sciencemag.org] and fulltext [sciencemag.org] links.

finding out what we're really made of (0)

Anonymous Coward | more than 5 years ago | (#26333639)

unfortunately for some, that will prove that our spirit is our outstanding feature.

Old news (0)

Anonymous Coward | more than 5 years ago | (#26333677)

The only Science article on this topic was published in 2006: http://www.sciencemag.org/cgi/content/summary/311/5767/1544. It won't be new news again until the product ships - supposedly in 2010

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