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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.

Related Stories

A MARC in the Silicon: Sequencing E. coli with the MinION 12 comments

I am part of an international team of researchers who have been exploring the capabilities of the MinION Sequencer, the MinION Analysis and Reference Consortium (MARC). Our first paper on this exploration has just been published in f1000 Research. Five separate labs carried out four sequencing runs each of the same strain of E. coli, and a few more labs helped to analyse the results. If you're interested in seeing what this technology is capable of (or at least, what it was capable of about 6 months ago), check out the paper here, or download the data here.

The Oxford Nanopore MinION is a small DNA sequencer that plugs into the USB port of a laptop and sequences DNA by measuring changes in an electric current as the sequence is passed through one of 4096 pores in the sequencing device. These electrical signals are combined into events that describe the movement of a single base, and the events are then base-called to generate DNA sequences.

The MinION sequencer is almost entirely electronic, stripping away everything that makes existing DNA sequencing technologies big, heavy, slow and expensive. This has meant that the MinION is uniquely able to be used in remote areas where other sequencers just can't reach: sequencing Ebola on-site in Africa, sequencing the DNA of small frogs in the Amazon rainforest, and more recently sequencing DNA in NASA's vomit comet.

Previously: The MinION - Genome Sequencing in a Handheld Device


Original Submission

TEDxWellington Talk: Sequencing that Stimulates the Sensors; Author Q&A 29 comments

[Ed note: We are experimenting with something new with this story on SoylentNews. The submitter has agreed to answer some of your questions. Please submit one question per comment. The most highly-rated comments will be given to the submitter. We'll post another story later with the replies.

Previous stories on MinION:

The MinION - Genome Sequencing in a Handheld Device
A MARC in the Silicon: Sequencing E. coli with the MinION]

I was invited to be a speaker at the TEDxWellington 2016 conference on 6th March. The theme of the conference was trust. Along with all other speakers and crew, I was trusted not to tell anyone about my role in it until I had finished speaking. Attendees were transported from a meeting place at the National War Memorial to the venue in buses that had been blacked out The conference was the first public event that was held inside Peter Jackson's private cinema at Park Road Post Production in Miramar, Wellington, New Zealand.

Due to an enclosed fabric tunnel, the cinema inside the venue was the first thing that attendees saw after getting into the buses. Only a few people knew the speaker lineup, and speakers for the second and third sessions were distributed throughout the audience, so that attendees couldn't tell who else would be talking.

The talks, prior to post-production and editing are available on a live stream feed. My talk was about DNA sequencing using the Oxford Nanopore MinION and starts at timecode 01:29:00 on the recorded video. A video of my presentation will be edited and uploaded to the TEDx YouTube channel in a few weeks.

Here's a brief point summary of my talk:

[Continues.]

Weird Science Heading to the ISS 5 comments

Writing at Space.com, Sarah Lewin describes some of the scientific cargo that tomorrow's Dragon9 launch will carry to the International Space Station:

SpaceX's ninth commercial cargo mission, launching early Monday (July 18), is lugging a selection of strange science to the International Space Station -- living, beating heart cells, microbes from a nuclear disaster, a tiny DNA sequencer and more.

[...] One experiment won't take up a lot of space, but it has the potential to be a huge research boon to the orbiting lab -- the space station's first DNA sequencer, which is about the size of a "fun-size Snickers bar," said Sarah Wallace, a microbiologist at Johnson Space Center (JSC) in Houston.

[...] The astronauts will also be bringing aboard live heart cells, which they will cultivate for one month to test for changes in their sizes, shapes and beating patterns.

[...] Another experiment that investigates bone loss in space will test some technology that could potentially save researchers from sending similar experiments aloft: It will compare changes in bone cells that have been flown to space with ones that got the zero-g experience on Earth, levitated magnetically in a microgravity simulator.

[...] In addition to sending up those heart and bone cells, plus some tomato seeds that will be grown in schools once they return to Earth, the spacecraft is bringing another strange visitor: microbes that emerged after the Chernobyl nuclear reactor, located in Ukraine, melted down catastrophically in 1986.

[...] Researchers are also sending up a demo of a phase-change material heat exchanger, which will test wax-based and water-based substances that can melt and freeze as the temperature outside a spacecraft changes, absorbing excess heat and re-releasing it to keep the craft warm as it orbits in and out of Earth's shadow, going from blazing heat to chilling cold. They're also testing a receiver that will track ships on the ocean, computer processors to stick outside the station and check for radiation-related errors, and a more efficient solar cell.

The photo of the DNA sequencer shows that it really does resemble a "fun-size Snickers bar", though with two layers!

The "DNA sequencer" is made by Oxford Nanopore Technologies and is called MinION about which we have had a few stories posted here.

Related:
SpaceX Set to Launch 9th Dragon CRS Mission 12:45am EDT (04:45am UTC) on July 18


Original Submission

Human Genome Sequenced With MinION Nanopore Sequencer 3 comments

Pocket-Size Nanopore Device Sequences Entire Human Genome

Researchers have assembled the entire human genome using a nanopore sequencer, according to a study published today (January 29) in Nature Biotechnology [open, DOI: 10.1038/nbt.4060] [DX]. Using a pocket-size device, dubbed MinION, the team was able to fill 12 gaps in the sequenced human genome by achieving reads of DNA sequences nearly one million bases in length—the longest to date.

Also at BBC.

Nanopore sequencing and assembly of a human genome with ultra-long reads (linked above)

We report the sequencing and assembly of a reference genome for the human GM12878 Utah/Ceph cell line using the MinION (Oxford Nanopore Technologies) nanopore sequencer. 91.2 Gb of sequence data, representing ∼30× theoretical coverage, were produced. Reference-based alignment enabled detection of large structural variants and epigenetic modifications. De novo assembly of nanopore reads alone yielded a contiguous assembly (NG50 ∼3 Mb). We developed a protocol to generate ultra-long reads (N50 > 100 kb, read lengths up to 882 kb). Incorporating an additional 5× coverage of these ultra-long reads more than doubled the assembly contiguity (NG50 ∼6.4 Mb). The final assembled genome was 2,867 million bases in size, covering 85.8% of the reference. Assembly accuracy, after incorporating complementary short-read sequencing data, exceeded 99.8%. Ultra-long reads enabled assembly and phasing of the 4-Mb major histocompatibility complex (MHC) locus in its entirety, measurement of telomere repeat length, and closure of gaps in the reference human genome assembly GRCh38.

Previously: The MinION - Genome Sequencing in a Handheld Device
A MARC in the Silicon: Sequencing E. coli with the MinION
Update: Sequencing That Stimulates the Sensors, and MinION Q&A Responses

Related: 3D Genome Assembly Could Create a Human Reference Genome for Under $10,000


Original Submission

Biotech and Biohackers at SXSW 20 comments

Pharmaceutical giants are holding sessions about topics such as childhood cancer and anti-aging drugs at South by Southwest (SXSW). But it is the lightly regulated "biohacks" that seem to get all of the attention:

"I'm here to make the argument that you have a moral imperative, if you're an employer, to hack your employees," said Dave Asprey, founder of Bulletproof 360, during a session called "Would You Let Your Boss Biohack You?"

Asprey's company sells products with names like Brain Octane Oil, containing supplements Silicon Valley calls nootropics, which are purported to enhance cognitive function. He is also a biohacker. That means he takes nootropics to improve his performance in life, refuses to ingest a long list of chemicals that includes fluoride, and averages six hours and six minutes of sleep every night. During his talk, Asprey was wearing sienna-toned sunglasses, which, he explained, were hacking the light.

At Bulletproof, every employee has access to nootropics and is encouraged to expand his or her mind accordingly. Asprey is particularly fond of modafinil, which he calls "the Limitless drug" in reference to a 2011 movie in which Bradley Cooper finds a pill that makes him a genius. Sold under the brand name Provigil, modafinil got Asprey through the Wharton School, he said, and it has "the safety profile of ibuprofen," a statement with which the Drug Enforcement Administration would disagree.

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  • (Score: 2) by kaszz on Thursday May 21 2015, @11:48PM

    by kaszz (4211) on Thursday May 21 2015, @11:48PM (#186254) Journal

    We are rapidly approaching the point where on the spot STD testing can be accomplished. Or "bad genes, procreation denied"..

    (expect the facebook slime to tap into this)

  • (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.

      --
      Ask me about Sequencing DNA in front of Linus Torvalds [youtube.com]
      • (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.

          --
          Ask me about Sequencing DNA in front of Linus Torvalds [youtube.com]
          • (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.

            --
            Everyone is entitled to his own opinion, but not to his own facts"- --Daniel Patrick Moynihan--
            • (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.

              --
              Everyone is entitled to his own opinion, but not to his own facts"- --Daniel Patrick Moynihan--
          • (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.

  • (Score: 3, Interesting) by takyon on Thursday May 21 2015, @11:56PM

    by takyon (881) <takyonNO@SPAMsoylentnews.org> on Thursday May 21 2015, @11:56PM (#186258) Journal

    http://www.theplatform.net/2015/03/25/a-light-approach-to-genomics-with-optical-processors/ [theplatform.net]

    These are all issues that TGAC considered during its massive sequencing effort to unravel the “simple” bread wheat genome. To do this and more human-focused genomic analyses, the center became home to one of the top systems in the world, utilizing a massive shared memory machine. TGAC has an SGI UV 2000 system with 2,500 “Sandy Bridge” Xeon cores and 20TB of shared memory—the latter a necessary feature to keep as much of the genome data in place for analysis versus moving to and from disk during sequence alignment. In essence, during this critical element of bioinformatics, the system seeks strings of DNA characters within a larger string (typically a genome) to find similar genes and thus determine common ancestry, for example. It’s like a complex, memory-intensive “spot the difference” puzzle, which means it can be useful to keep one entire genome (if possible) entirely in memory.

    But even with the performance and efficiency savings of a large shared memory machine, it’s still racking up major power and cooling costs. But what if it was possible for this type of processing to happen within a small desktop-sized machine that could plug into a standard main for power and process, on the spot, a human genome? If proven functional at scale, optical processors could displace standard clusters for gene sequencing in a far more power efficient way—there is little heat generated, especially compared to silicon technologies. And even more interesting, what if memory and the scalability limits therein were no longer a concern?

    These “what ifs” seem to present a rather tall order, but TGAC is working with Optalysys on a prototype processor that uses low-power lasers instead of standard electronics for processing. The goal is to do this genomics work using 95 percent less power than standard processing technologies.

    ∑☣ ≤ 🏃🏃🏃 👽

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  • (Score: 3, Insightful) by takyon on Friday May 22 2015, @12:14AM

    by takyon (881) <takyonNO@SPAMsoylentnews.org> on Friday May 22 2015, @12:14AM (#186262) Journal

    Careful, criminals. [nydailynews.com]

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