Slashdot Mirror


New Method To Revolutionize DNA Sequencing

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.'"

48 of 239 comments (clear)

  1. 99.3% accurate? by Valdrax · · Score: 4, 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?

    --
    If it's for-profit but free, you're not the customer -- you're the product (e.g., the Slashdot Beta's "audience").
    1. Re:99.3% accurate? by imamac · · Score: 4, 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?

    2. Re:99.3% accurate? by aoeusnth · · Score: 2, 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?

      More than good enough for forensic work at least, I'd wager.

    3. Re:99.3% accurate? by Maximum+Prophet · · Score: 4, Interesting

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

      --
      All ideas^H^H^H^H^Hprocesses in this post are Patent Pending. (as well as the process of patenting all postings)
    4. Re:99.3% accurate? by Anonymous Coward · · 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.

    5. Re:99.3% accurate? by ccguy · · Score: 4, Insightful

      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)

    6. Re:99.3% accurate? by morgan_greywolf · · Score: 5, Funny

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

    7. Re:99.3% accurate? by Anonymous Coward · · Score: 2, Insightful

      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..

    8. Re:99.3% accurate? by evilNomad · · Score: 2, Funny

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

    9. Re:99.3% accurate? by Rayban · · Score: 2, Funny

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

      --
      æeee!
    10. Re:99.3% accurate? by scorp1us · · 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.

      --
      Slashdot's rate-of-post filter: Preventing you from posting too many great ideas at once.
    11. Re:99.3% accurate? by shaitand · · Score: 4, 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.

    12. Re:99.3% accurate? by prograde · · Score: 2, Informative

      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.

    13. Re:99.3% accurate? by fracai · · Score: 3, 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 /".

      --
      -- i am jack's amusing sig file
    14. Re:99.3% accurate? by peter303 · · Score: 4, Informative

      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.

    15. Re:99.3% accurate? by MyLongNickName · · Score: 2, 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.

      --
      See my journal for slashdot ID's by year. Mine created in 2005. http://slashdot.org/journal/289875/slashdot-ids-by-year
    16. Re:99.3% accurate? by Adriax · · Score: 4, 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.

      --
      I don't suffer from insanity, I enjoy every minute of it!
    17. Re:99.3% accurate? by jd · · Score: 2, Funny

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

      --
      It's a small world and it smells funny; I'd buy another if it wasn't for the money; Take back what I paid (SoM)
    18. Re:99.3% accurate? by Anonymous Coward · · Score: 2, Informative

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

    19. Re:99.3% accurate? by m93 · · Score: 2, Insightful

      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?

      It's most likely good enough to deny you health coverage. Pre-existing condition? Now risk can be assessed on pre-existing genes.

    20. Re:99.3% accurate? by TooMuchToDo · · Score: 3, 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."

    21. Re:99.3% accurate? by amalyn · · Score: 2, Interesting

      Systematic errors could be identified by correlating results with other DNA sequencing results.

      Using a large sample, like the proposed Personal Genome Project [unsure if they have gotten in touch with any of those who expressed interest in participating] could be useful in showing any systematic mis-reads, as long as the Personal Genome Project is using another method to sequence the participant's DNA.

  2. Sub-$1000 genome sequencing by morgan_greywolf · · 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!

    1. Re:Sub-$1000 genome sequencing by Ethanol-fueled · · Score: 3, Funny

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

      Hopefully you'll fix that nasty intercalary deletion bug first!

    2. Re:Sub-$1000 genome sequencing by morgan_greywolf · · Score: 2, Funny

      I will, but I gotta P first!

    3. Re:Sub-$1000 genome sequencing by CorporateSuit · · Score: 2, Funny

      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.

      --
      I am the richest astronaut ever to win the superbowl.
  3. Real-Time DNA Sequencing from Single Polymerase Mo by mapkinase · · Score: 2, Informative

    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.

    --
    I do not believe in karma. "Funny"=-6. Do good and forbid evil. Yours, Oft-Offtopic Flamebaiting Troll.
  4. Kicks ass on Moore's Law... by djupedal · · Score: 4, Insightful

    > 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' :)

  5. error correction by bugs2squash · · Score: 2, Insightful

    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 ?

    --
    Nullius in verba
    1. Re:error correction by Hurricane78 · · Score: 5, Insightful

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

      --
      Any sufficiently advanced intelligence is indistinguishable from stupidity.
  6. Article in Science by prograde · · 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

  7. I guess I can drop my X prize plans by damn_registrars · · Score: 2, Informative

    Since this technique should be a shoe-in for the Archon X Prize.

    --
    Damn_registrars has no butt-hole. Damn_registrars has no use for a butt-hole.
  8. Re:Bad summary by damn_registrars · · Score: 2, Insightful

    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.

    --
    Damn_registrars has no butt-hole. Damn_registrars has no use for a butt-hole.
  9. Slashdotted: Abstract and Fulltext by chihowa · · Score: 2, Informative

    It looks to be inaccessible. Here are the abstract and fulltext links.

    --
    If you want a vision of the future, imagine a youtube comments section scrolling - forever.
  10. Re:GATTACA is here by oni · · Score: 2, Funny

    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.

  11. Re:Battle Tactics :) by timeOday · · Score: 2, Insightful

    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.

  12. Re:Bad summary by nodrogluap · · Score: 2, Insightful

    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.

  13. nitpick by Zenaku · · Score: 2, Informative

    One base-pair does not a gene make.

    --
    If fate makes you a motorcycle, you become a motorcycle.
    1. Re:nitpick by TheMeuge · · Score: 2, Insightful

      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.

  14. Re:maybe 60 to 1000 are significant? by nwf · · Score: 2, Insightful

    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 likely.

    --
    I don't know, but it works for me.
  15. Grammar ambiguity by nsayer · · Score: 2, 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?

  16. Re:99.999% accuracy by gnick · · Score: 2, Funny

    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.

    --
    He's getting rather old, but he's a good mouse.
  17. New Scientist Write Up by Fnord666 · · Score: 2, Informative

    Here is an article in New Scientist about the new process. It explains it fairly well and even defines what a ZMW is.

    --
    'The tyrant will always find pretext for his tyranny.' - Aesop's Fables
  18. Error Correction by LUH+3418 · · Score: 2, Insightful

    Many people seem concerned about the reading error rate. However, as it's been pointed out, it should be easy enough to read a DNA sequence multiple times (or read the whole genome multiple times) to decrease the error rate significantly. If you have one chip that can read the entire human genome in 30 mins, you can have the same chip read it twice in an hour, or four chips reading four copies in 30 mins.

    Furthermore, if you're using a technique like this to map a person's genome, you can be clever about it. Base pairs code genes, which is something you can take into account. For example, if you're reading the eye color gene, and your machine somehow consistently makes mistakes in that area, you can compare your reads to the few possible known eye color genes, and pick the most likely based on the genetic sequences of the entire gene.

  19. Re:cost of sequencing is a reasonable determinant by CrankinOut · · Score: 2, Insightful
    If the article had stated that the cost were $1,000,000 to do the sequence, then the potential applications of the technology would be severely limited. Getting the cost (not the charge for the service) down creates the opportunity for more studies to be performed, more financial accessibility for patients, and less resistance for insurance companies or Medicare to deny charging for the study when it's indicated.

    In medicine, the cost of a study, as well as its reliability, availability, and predictive value, enters into the decisions made in clinical management.

  20. Reading a sequence is not the same as creating one by CrankinOut · · Score: 2, Insightful
    Just as seeing the moon doesn't require the same amount of effort as landing on it, reading a DNA sequence doesn't mean that selective modification is "just around the corner."

    Real applications of this, however, include looking for gene sequences in adults which predispose them to diseases (e.g. breast cancer) and then providing counseling and monitoring commensurate with that risk, a far less expensive effort than monitoring everyone for the same disease, even if they aren't at risk. Also, one could use this on embryonic cells obtained through amniocentesis to screen for hereditary diseases is families where there are risk factors.

  21. Re:Gattica... by Noddegamra · · Score: 2, Informative

    Since inosine.

  22. It does not rock by pnotequalsnp · · Score: 2, Interesting

    Considering current sequencing technology generates terabytes of data per day (see the Sanger center), then wouldn't it be efficient to maximize the amount of information per pixel (i.e. per byte)? This method is actually is much worse (orders of magnitude) than the current method. There are many other problems with what they do, but hopefully the cash infusion can last them another 2 years until the write a paper like this. BTW, the say that appropriate camera tech. will be available in 2-5 years, but they're ready now! They might be buying time...