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posted by janrinok on Thursday May 21 2015, @11:26PM   Printer-friendly

[Editor's Comment: This article might sound a bit like a soyvertisement but it has been submitted by one of our community and someone who is well qualified in his field - David Eccles from the Malaghan Institute of Medical Research in New Zealand. It is interesting to read about what is considered currently to be state of the art in field genome sequencing.]

On the 14th and 15th of May, 2015, Oxford Nanopore Technologies held their inaugural nanopore sequencing conference, London Calling. The conference was set up to inform people about the current progress of Oxford Nanopore's first sequencing device, the muesli bar-sized, USB-powered MinION. Over 250 people were in attendance at the conference, representing 35 countries, including two from New Zealand: Nicole Moore from Environmental Science and Research, and David Eccles from the Malaghan Insititute of Medical Research. Over the course of two days, these attendees discovered how the MinION is quietly turning the world of sequencing inside out.

Everything needed for sample preparation and sequencing can fit into a single piece of checked luggage on an airplane. The MinION is robust enough to make it across unsealed roads to remote parts of Africa, where it has been used for sequencing on-location during the Ebola outbreak. The MinION has also been put through its paces for tracking the traffic of organisms. Detection at the species level can be achieved in under 20 minutes of sequencing, and very subtle changes for the same species from different origins can be identified in less than an hour.

Clive Brown, Chief Technical Officer for Oxford Nanopore Technologies, gave a brief summary of what is to come in the near future of nanopore sequencing:

  • A fast mode for sequencing, allowing a human genome to be sequenced with high reliability in a 2-day run.
  • An improved Mk II sequencer, with six time the throughput and six times the run time of the first sequencer.
  • A clip-on sample preparation laboratory (Voltrax), allowing preparation and sequencing directly from blood in 20 minutes.
  • Time-based pricing, reducing the minimum cost of a single-molecule sequencing run to $50.
  • A 48-cell desktop sequencing device (PromethION) that can produce over 6 terabases of sequence per day, making sample preparation time the slowest part of the sequencing process.
 
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  • (Score: 2) by takyon on Thursday May 21 2015, @11:48PM

    by takyon (881) <takyonNO@SPAMsoylentnews.org> on Thursday May 21 2015, @11:48PM (#186255) Journal

    Is genome sequencing cost [genome.gov] going to decline some more? It has been stagnant lately.

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  • (Score: 4, Informative) by gringer on Thursday May 21 2015, @11:57PM

    by gringer (962) on Thursday May 21 2015, @11:57PM (#186260)

    Yes, it will. The newer flow cells in the works will have all the signal processing in the sequencer (currently the processing circuits are included in the flow cell), reducing the consumable component to plastic with a bit of embedded gel -- very easy to mass produce at low cost.

    With the Mk II USB sequencer, Clive Brown claimed that a 21-hour run would get suitable coverage for a human genome for $1000, and that's non-amortized up-front cost (i.e. no "human genome only, pay $15 million first, and then average cost over 5 years"). The PromethION will have a "ridiculously low cost", although the specifics of that were not mentioned.

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    • (Score: 2) by kaszz on Friday May 22 2015, @12:09AM

      by kaszz (4211) on Friday May 22 2015, @12:09AM (#186261) Journal

      Can one sequence specific bits of the genome to reduce cost? is it possible to automatically sniff pieces of dead skin etc from the air and sequence directly? Can this sequencing unit be ordered? What's really inside the box? Any further price drops on the horizon, ie technically possible but not yet explored?

      • (Score: 5, Informative) by gringer on Friday May 22 2015, @01:27AM

        by gringer (962) on Friday May 22 2015, @01:27AM (#186277)
        1. Yes, targeted sequencing is certainly a good way to reduce the costs. With a combination of targeted sequencing and sample multiplexing via DNA barcoding, you get very accurate (i.e. high coverage) sequences at very low cost.
        2. Automated sampling is not currently possible, but I can imagine that someone will soon work out some clever way to do that. Voltrax is almost there, but still requires a bit of manual pipetting to convert samples into sequences.
        3. The sequencing unit can be ordered by signing up to the access programme [nanoporetech.com]. Despite it's name, the MinION Access Programme is the commercialisation of the sequencing device. Presumably my bit regarding that part was removed from my submission because it was a bit too advertisey.
        4. Details about "what's in the box" can be found on the Oxford Nanopore website [nanoporetech.com]. To try to summarise: 512 very high precision isolated electrical sensors for 2048 sequencing channels, synthetic polymer membrane, protein nanopores, buffer liquids to keep the pores happy, electrical components to deliver a potential across the pore, and a USB cable to transfer sensor readings to a laptop.
        5. As far as I'm aware, ONT is pricing their devices based on the available competition (and demand). They have a lot of room for movement in price if (for example) a competitor magically discovered a way to make sequencing by synthesis more affordable.

        To tone down the buzz a little bit, the conference itself was definitely a big advertising venture on ONT's part. They selected people who were good performers in the MinION community to talk about the research that they'd done, but there are plenty of others in the community who are still struggling with getting the thing to work properly. Having said that, it's unlikely people would be interested in attending a conference where everyone spoke about all the things they weren't able to do.

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        • (Score: 2) by opinionated_science on Friday May 22 2015, @01:40AM

          by opinionated_science (4031) on Friday May 22 2015, @01:40AM (#186283)

          I am quite glad something is finally approaching the market, it has been a long time coming...

          Hopefully the cost of 30x human will drop to $250 or less, so National Geographic can organise it. I am not joking! I think they have done a great deal to raise awareness of the utility of DNA sequencing.

        • (Score: 2) by TLA on Friday May 22 2015, @02:05PM

          by TLA (5128) on Friday May 22 2015, @02:05PM (#186454) Journal

          Given the device's name, does it come in a giant Kinder egg wrapped in a pair of dungarees?

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    • (Score: 2) by Adamsjas on Friday May 22 2015, @12:17AM

      by Adamsjas (4507) on Friday May 22 2015, @12:17AM (#186264)

      What about the commercial market, small labs specializing in (you can probably guess) Paternity, or police departments working on their backlog**? Is this gear even remotely suitable for that type of work, where specimen matching is just about the only criteria?

      Can pared down versions of this be made targeted at that sort of market?

      **See:
      http://www.npr.org/2015/05/20/408293080/untested-rape-kit-backlog-represents-a-public-safety-issue-in-u-s [npr.org]

      • (Score: 2) by gringer on Friday May 22 2015, @01:38AM

        by gringer (962) on Friday May 22 2015, @01:38AM (#186282)

        Can pared down versions of this be made targeted at that sort of market?

        You can't really get more "pared down" than the MinION. At that $50 (NZD) minimum cost per run, it would be possible to barcode and multiplex up to 96 samples, so you could theoretically get the cost of high-throughput sequencing down to less than $1 per sample. However, sample preparation cost would then be a much larger component of the cost. I think the Voltrax in its current state will do 4 samples at a time, so that's about $15 per sample without any additional sample preparation effort.

        With targeted sequencing (as would be the case for forensic or paternity testing), you could quite easily get adequate coverage with 5Gbp of sequence (for a 1h run) spread across 96 samples.

        --
        Ask me about Sequencing DNA in front of Linus Torvalds [youtube.com]
        • (Score: 2) by captain normal on Friday May 22 2015, @05:12AM

          by captain normal (2205) on Friday May 22 2015, @05:12AM (#186328)

          Still I can see it actually improving forensic DNA analyses to near CSI (the TV series) speed. The really amazing stuff will be in speeding up medical diagnostics.

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          • (Score: 2) by captain normal on Friday May 22 2015, @05:17AM

            by captain normal (2205) on Friday May 22 2015, @05:17AM (#186329)

            Let me add to that. This looks to be a step closer to Bones McCoy's hand held diagnostics scanner.

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        • (Score: 0) by Anonymous Coward on Saturday May 23 2015, @09:38AM

          by Anonymous Coward on Saturday May 23 2015, @09:38AM (#186815)

          Can you explain precisely what they mean by "genome sequence"? I think of the dna content of a single cell reported as 46 strings of GATC, each of a length however long the individual chromosomes are. One issue is that this will differ from cell to cell.