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Nanopore MinION – $1k solid-state DNA sequencers

nanoporetech.com

51–60 of 111 posts

Re: Nanopore MinION – $1k solid-state DNA sequencers

#51
post #8

I just ran a couple of flowcells last week. I've ran 8 total so far now. My impression is that it can be very inconsistent depending on the quality of the flowcell that they send you and your DNA prep. Great for smallish genomes (bacteria), not enough throughput/quality for large eukaryotic genomes (1gb+) unless you got money to burn.

It’s also comparatively expensive compared to other platforms (you can get a full human genome sequenced at high coverage for between 1000 and 3000 USD). The error rate is stupidly high (somewhere between 10 and 20%) compared to Illumina or Ion Torrent who give error rates far less than 1%. It can give very long reads, which are useful in some niche applications. But it’s been massively over-hyped (and over capitaliz…

> you can get a full human genome sequenced at high coverage for between 1000 and 3000 USD

This is not a "full" human genome, but a collection of 150bp fragments that can be realigned to an existing human genome. You cannot take this and infer the whole diploid genome of the individual. There is a huge amount that will be missed, and all of our current knowledge is based on this gappy picture of what's going on in single genomes and human populations.

> It can give very long reads, which are useful in some niche applications. But it’s been massively over-hyped (and over capitalized).

I think you're dismissing the technology out of hand because of biases derived from much more limited short-read technology that only allows us to reliably see small variants Without these long reads we can't see structural variation (SVs). There is an increasing amount of evidence that much of adaptive variation is driven by these kinds of variants. If you want recent evidence, see https://www.nature.com/articles/s41588-017-0010-y. There has long been evidence that there are huge copy number variations in humans, but these are still not evaluated reliably: http://science.sciencemag.org/content/330/6004/641.

We should be open to the possibility that our observational techniques are limiting our understanding how how genomes work. This has consistently occurred in the history of every observationally-driven science.

It's amusing to me that people assume that SVs are "niche" when even the limited surveys of genomes we've been able to do with short reads show that roughly an equal number of base pairs in the human population vary due to small variants like SNPs and indels and big ones like deletions, insertions, and large scale copy number variation: http://science.sciencemag.org/content/330/6004/641

Re: Nanopore MinION – $1k solid-state DNA sequencers

#53
post #51

Earlier quoted context omitted.

It’s also comparatively expensive compared to other platforms (you can get a full human genome sequenced at high coverage for between 1000 and 3000 USD). The error rate is stupidly high (somewhere between 10 and 20%) compared to Illumina or Ion Torrent who give error rates far less than 1%. It can give very long reads, which are useful in some niche applications. But it’s been massively over-hyped (and over capitaliz…

> you can get a full human genome sequenced at high coverage for between 1000 and 3000 USD This is not a "full" human genome, but a collection of 150bp fragments that can be realigned to an existing human genome. You cannot take this and infer the whole diploid genome of the individual. There is a huge amount that will be missed, and all of our current knowledge is based on this gappy picture of what's going on in si…

I’d agree with you, that long reads would be useful if the error rate wasn’t so shockingly bad.

There is, likely value in long reads, but what non-niche research applications are there for highly error’d reads that justify a valuation of several billion dollars?

Re: Nanopore MinION – $1k solid-state DNA sequencers

#55
post #51

Earlier quoted context omitted.

> you can get a full human genome sequenced at high coverage for between 1000 and 3000 USD This is not a "full" human genome, but a collection of 150bp fragments that can be realigned to an existing human genome. You cannot take this and infer the whole diploid genome of the individual. There is a huge amount that will be missed, and all of our current knowledge is based on this gappy picture of what's going on in si…

I’d agree with you, that long reads would be useful if the error rate wasn’t so shockingly bad. There is, likely value in long reads, but what non-niche research applications are there for highly error’d reads that justify a valuation of several billion dollars?

I feel like there is or was an assumption they'd be able to improve their tech

Re: Nanopore MinION – $1k solid-state DNA sequencers

#56

Oxford Nanopore is burning through at least $1 million a week of their investors income with virtually no sales to support their market valuation. Will they be the next Theranos? https://www.jcapitalresearch.com/uploads/2/0/0/3/20032477/20...

Maybe it's just the company's spin, but apparently they are not keeping up with the orders. Also, the technology is working, and it is working competetively well for certain applications.

Re: Nanopore MinION – $1k solid-state DNA sequencers

#57
post #50

I'm pretty sure we are now just a couple of marketing cycles away from a version of this being re-packaged and sold to police departments around the world as a tool for identifying suspects in a cloud database of DNA sequences belonging to People of Interest. (You don't need a complete sequence for that, just enough unique markers to ID somebody.) Goodbye "papers, please", hello "cheek swab, please".

Too expensive with the current nanopore technology.

And with any other technology, including a miniaturized PCR implementation, it would be too slow.

Re: Nanopore MinION – $1k solid-state DNA sequencers

#58

For an interesting contrast, here's a look inside two DNA sequencers from the last decade, costing two orders of magnitude more (and also roughly two orders of magnitude larger in volume and weight): https://www.youtube.com/watch?v=XaumUp4GpCw https://www.youtube.com/watch?v=3K9whMm7vvc It's almost like Moore's law.

They are orders of magnitude more precise, and this is the important part. A human genome has 3 billion basepairs, even if you have 99,99% accuracy, this is not enough.

99,99% accuracy is enough, especially if you need 30X coverage.

Also, the initial Human genome wasn't that good either...

Re: Nanopore MinION – $1k solid-state DNA sequencers

#59
post #51

Earlier quoted context omitted.

It’s also comparatively expensive compared to other platforms (you can get a full human genome sequenced at high coverage for between 1000 and 3000 USD). The error rate is stupidly high (somewhere between 10 and 20%) compared to Illumina or Ion Torrent who give error rates far less than 1%. It can give very long reads, which are useful in some niche applications. But it’s been massively over-hyped (and over capitaliz…

> you can get a full human genome sequenced at high coverage for between 1000 and 3000 USD This is not a "full" human genome, but a collection of 150bp fragments that can be realigned to an existing human genome. You cannot take this and infer the whole diploid genome of the individual. There is a huge amount that will be missed, and all of our current knowledge is based on this gappy picture of what's going on in si…

I think you are not sufficiently recognising how much structural variation can be resolved from short reads. There is certainly some that can't but a large proportion can be with the right tools.
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