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 capitalized).
The neat thing is that it’s very small. But that isn’t really compelling given the very low accuracy.
$1,000 for the starter pack - what kind of use can you get out of that, and how much are the ongoing costs for the flowcells and anything else that needs to be replenished?
Are you using it for fun? professionally? academically?
I remember looking into this device before, but as I recall it was intended for small bacterial genomes. A quick Google turns up that a paper using the device to sequence a human genome has only just been published [0] hence the update to the website. I'm not at all familiar with the technology, but doesn't the fact that experts have only just now been able to sequence human DNA mean it would be pretty unlikely the device could be used as-is for "production" usage?
A few years ago, the sequencing field was really excited for this platform as an alternative/competitor to Illumina. Unfortunately, the MinION platform has never been able to generate enough high-quality data for most eukaryotic sequencing use cases. The MinION still has it's niche... long read sequencing can resolve problematic regions of the genome, and the minION is the only option for rapid sequencing in the field. For production genome sequencing centers though, Illumina's still the dominant tech. Their HiSeq X platform can put out a human genome right about $1k.
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):
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.
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.)
There was a cool visualization from data produced on nanopore on /r/dataisbeautiful recently [1]. It really shows the strengths of the device - ~50kb region with 3kb imperfect repeats. This would be impossible to align properly with <1kb reads from illumina. The paper is worth a read if you're interested in sequencing. They basically did a de novo sequencing of a bacterial genome on the cheap. And in the assembly they had more than 1000 reads longer than 100kb. Using this in combination with an Illumina sequencer is probably the best though.
That’s great, but for a company that has raised on a valuation of >2BUSD how are they going to compete with Illumina.
The read lengths might be long, but the error rate is a couple of orders of magnitude higher. I can’t see a market large enough for highly error’d log reads to support their valuation.
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?
I'm somewhat confused by that article, one of its key pieces of data (saying that a full human genome sequence would cost $90,000 using this technology) comes from an expert comment made on Quora. The Quora post made the $90,000 estimate in early 2016, then updated it in July 2017 to $10,000. This article was written in December 2017, so why does it use the original figure and not the updated one?
The technology really works and is generating results at a rapid pace. This will absolutely not be the next Theranos, although you may be right that there are issues of burnrate and maybe even mismanagement.
To me the fact that they have a patent monopoly on "putting DNA through a protein pore with voltage sensing" is tragic. Who knows were we would be today if these patents had been granted to the public domain.
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.
One thing I'm excited for here is targeted sequencing using read-until. In this method, you monitor the current trace coming off of individual pores, and if you determine that the DNA in that pore is not part of your sequence of interest, you can reverse the voltage to remove the DNA and start sequencing another molecule. I think this will open up a lot of applications for human genomics.
If you're interested in Oxford Nanopore, you might also keep an eye out for Roswell Biotechnologies (https://www.genomeweb.com/sequencing/roswell-biotechnologies...). TL;DR: their sequencer involves immobilizing polymerases in circuits so you can measure the current changes that occur as the polymerase adds bases to a strand. This might be a good approach, since it doesn't involve optics (like IonTorrent and minION, keeping costs down) and you get a current event per base (as opposed to per 5-6 bases as with minION), making basecalling easier and potentially more accurate. And it will be fast, since you're reading as fast as the polymerase can work. They want to get up to 10kb reads, and I imagine they could increase the consensus accuracy per read by looping around a single molecule of DNA several times, like with PacBio. Seems feasible too (after all, PacBio has successfully been able to integrate polymerases into very small features rather well, so I see no showstoppers there).
There is a group in UK (Matt Loose's group) that I think is working a lot on read-until. I haven't really kept up with it. I think the key for read-until to work is ultimately probably going to be better hardware as you need to be able to analyze the trace signal and compare it against a database fast enough to tell the device to kick it out. There are plenty of software optimizations that can be done to compress the signal or extract relevant regions, but the comparison to a database will be difficult to do fast.
Read-until has had diminishing utility. Over the last year or so, the speed at which a read can pass through the pore has increased so that by the time you call the bases and determine what it is, the read is likely to have already passed through the pore.
Since 2013, Illumina's brought the price of a genome to about $1k with the HiSeq X, which essentially scales up their existing tech. No idea what the next few years hold, but I'm excited to see insurance companies beginning to cover genome sequencing as an affordable diagnostic tool.
I think I could help answer this. The cost of computation has gone down so much that its just a fraction of the price for your whole genome sequencing. The cost comes from preparation, reagents, and storage. Illumina sells their own reagents, so the cost is really dependent on them. We've worked really hard to get the computation cost of genome sequencing as low as possible, and we just passed a major milestone last year.
Source: Software Engineer for a well-known non-profit sequencing lab/center.
I think we're already there. You can probably get around a $50 dollar bacterial genome by using robots and doing 384-well plates of samples at a time to get economies of scale.
A lot of the costs are outside of the sequencing itself. You have to extract the DNA from the sample and prepare that DNA for the sequencing platform you're using. These costs are both the reagents needed to do this, and also the associated labour costs, even when done at scale.
Perhaps you meant $100 human genome though? However I think roughly the same principles apply.
You're buying a service for the 500-800$. Here you're buying a flowcell for 1000$ (the "sequencer" is more or less free). The technology is pretty different and a lot more bleeding edge. If what you want is just a genome aligned to a known reference and you can wait a few days then this is not what you want.
We use ONT's minION for strange niche stuff, where either the DNA prep method matters or the latency (the time from loading to the first data out of the machine) matters. Read quality is typically not as good as illumina, so for applications where we need quality we stick with the NextSeq. There's no reason to think nanopore technology won't get better though, but for now, if you've got the money illumina is still the way to go most of the time.
There is a good reply to you that is currently dead for some reason, so I’m reposting it here for people who don’t have dead visible:
>
You're buying a service for the 500-800$. Here you're buying a flowcell for 1000$ (the "sequencer" is more or less free). The technology is pretty different and a lot more bleeding edge. If what you want is just a genome aligned to a known reference and you can wait a few days then this is not what you want.
We use ONT's minION for strange niche stuff, where either the DNA prep method matters or the latency (the time from loading to the first data out of the machine) matters. Read quality is typically not as good as illumina, so for applications where we need quality we stick with the NextSeq. There's no reason to think nanopore technology won't get better though, but for now, if you've got the money illumina is still the way to go most of the time.
>
The minion is a device you own. You don't need to ship the samples (which can be a problem, imagine ebola samples). You wait a maximum of 2 days for most of the results.
A more interesting race for bio-entrepreneurs. Rather than $1K human sized whole exome. May be the race to develop a $1 plasmid, BAC or small microbial genome sequencer. At that cost, seed level investment in single purpose bio-factories becomes very attractive.
As some that works in this industry the most amazing thing is the original sequencing technology (Sanger) is still going strong and about as much Sanger sequencing is being done now as back in the early 00s [0].
Can we ever imagine dna sequencing been done like a remoter sensor? E.g. automated sampling for e(environmental) dna,in-situ sequencing (single and multi species targeting), results transmitted back wirelessly. A biodiversity IoT system?
Yes, if you were willing to shell out 1000 bucks for the test, and if the bacteria was in your bloodstream (unlikely). If you swabbed, cultured, and sequenced, it'd be a better test.
I've personally used the oxford nanopore to diagnose malaria subtypes from ~1ml blood draws. Though it took awhile to do so, well beyond clinically relevant time periods. Our best turn around was about 2 days for sequence, but analysis takes much longer.
It's really comparing apples and oranges. If you want a 30x whole genome for genotyping, you'll use short read technologies and it'll be way less expensive.
The enormous reads offer a different window into genomes, by spanning repetitive regions where short reads can't be accurately placed. For lots of applications, the sweet spot is to use long reads for "scaffolding", then build up coverage with short reads.
[+] [-] daemonk|8 years ago|reply
[+] [-] comstock|8 years ago|reply
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 capitalized).
The neat thing is that it’s very small. But that isn’t really compelling given the very low accuracy.
[+] [-] oh_sigh|8 years ago|reply
Are you using it for fun? professionally? academically?
[+] [-] dooglius|8 years ago|reply
[0] https://sci-hub.la/downloads/8a73/[email protected]
[+] [-] atg_gcg_aca_aca|8 years ago|reply
[+] [-] dnautics|8 years ago|reply
[+] [-] userbinator|8 years ago|reply
https://www.youtube.com/watch?v=XaumUp4GpCw
https://www.youtube.com/watch?v=3K9whMm7vvc
It's almost like Moore's law.
[+] [-] Odenwaelder|8 years ago|reply
[+] [-] chrisamiller|8 years ago|reply
https://www.researchgate.net/profile/Orit_Shaer/publication/...
[+] [-] cstross|8 years ago|reply
(You don't need a complete sequence for that, just enough unique markers to ID somebody.)
Goodbye "papers, please", hello "cheek swab, please".
[+] [-] jrm5100|8 years ago|reply
This idea already here, but with technology based on older/simpler methods. One example is Intigenx: https://integenx.com/rapidhit-system/
The FBI has plans for implementing them: https://www.fbi.gov/news/testimony/fbis-plans-for-the-use-of.... The laws just need to catch up (or prevent it).
[+] [-] bayesian_horse|8 years ago|reply
And with any other technology, including a miniaturized PCR implementation, it would be too slow.
[+] [-] yread|8 years ago|reply
[1] https://www.reddit.com/r/dataisbeautiful/comments/7rpdr0/wev...
[+] [-] comstock|8 years ago|reply
The read lengths might be long, but the error rate is a couple of orders of magnitude higher. I can’t see a market large enough for highly error’d log reads to support their valuation.
[+] [-] sdcuevas|8 years ago|reply
https://www.jcapitalresearch.com/uploads/2/0/0/3/20032477/20...
[+] [-] Brakenshire|8 years ago|reply
[+] [-] eggie|8 years ago|reply
To me the fact that they have a patent monopoly on "putting DNA through a protein pore with voltage sensing" is tragic. Who knows were we would be today if these patents had been granted to the public domain.
[+] [-] bayesian_horse|8 years ago|reply
[+] [-] rotexo|8 years ago|reply
If you're interested in Oxford Nanopore, you might also keep an eye out for Roswell Biotechnologies (https://www.genomeweb.com/sequencing/roswell-biotechnologies...). TL;DR: their sequencer involves immobilizing polymerases in circuits so you can measure the current changes that occur as the polymerase adds bases to a strand. This might be a good approach, since it doesn't involve optics (like IonTorrent and minION, keeping costs down) and you get a current event per base (as opposed to per 5-6 bases as with minION), making basecalling easier and potentially more accurate. And it will be fast, since you're reading as fast as the polymerase can work. They want to get up to 10kb reads, and I imagine they could increase the consensus accuracy per read by looping around a single molecule of DNA several times, like with PacBio. Seems feasible too (after all, PacBio has successfully been able to integrate polymerases into very small features rather well, so I see no showstoppers there).
[+] [-] daemonk|8 years ago|reply
[+] [-] virusduck|8 years ago|reply
[+] [-] gourneau|8 years ago|reply
https://www.nasa.gov/mission_pages/station/research/news/dna...
[+] [-] GolDDranks|8 years ago|reply
[+] [-] atg_gcg_aca_aca|8 years ago|reply
Since 2013, Illumina's brought the price of a genome to about $1k with the HiSeq X, which essentially scales up their existing tech. No idea what the next few years hold, but I'm excited to see insurance companies beginning to cover genome sequencing as an affordable diagnostic tool.
[+] [-] tjridesbikes|8 years ago|reply
Source: Software Engineer for a well-known non-profit sequencing lab/center.
[+] [-] michaelbarton|8 years ago|reply
A lot of the costs are outside of the sequencing itself. You have to extract the DNA from the sample and prepare that DNA for the sequencing platform you're using. These costs are both the reagents needed to do this, and also the associated labour costs, even when done at scale.
Perhaps you meant $100 human genome though? However I think roughly the same principles apply.
[+] [-] drefanzor|8 years ago|reply
[+] [-] bayesian_horse|8 years ago|reply
[+] [-] m3nu|8 years ago|reply
Is this a similar product/result as buying whole genome sequencing from an established company for the $500 to $800 they charge these days?
[+] [-] aFLH7U2daj|8 years ago|reply
We use ONT's minION for strange niche stuff, where either the DNA prep method matters or the latency (the time from loading to the first data out of the machine) matters. Read quality is typically not as good as illumina, so for applications where we need quality we stick with the NextSeq. There's no reason to think nanopore technology won't get better though, but for now, if you've got the money illumina is still the way to go most of the time.
[+] [-] josephpmay|8 years ago|reply
> You're buying a service for the 500-800$. Here you're buying a flowcell for 1000$ (the "sequencer" is more or less free). The technology is pretty different and a lot more bleeding edge. If what you want is just a genome aligned to a known reference and you can wait a few days then this is not what you want. We use ONT's minION for strange niche stuff, where either the DNA prep method matters or the latency (the time from loading to the first data out of the machine) matters. Read quality is typically not as good as illumina, so for applications where we need quality we stick with the NextSeq. There's no reason to think nanopore technology won't get better though, but for now, if you've got the money illumina is still the way to go most of the time. >
[+] [-] bayesian_horse|8 years ago|reply
[+] [-] indescions_2018|8 years ago|reply
[+] [-] shrikant|8 years ago|reply
Here's some more detail on the tech works: https://www.mongodb.com/blog/post/oxford-nanopore-technologi...
[+] [-] aghillo|8 years ago|reply
[+] [-] danieltillett|8 years ago|reply
0. https://en.m.wikipedia.org/wiki/Sanger_sequencing
[+] [-] oliwarner|8 years ago|reply
[+] [-] rubidium|8 years ago|reply
It's remarkable the perverse economic rules that make disposables with vendor lockin a feature. Opex vs capex.
[+] [-] aghillo|8 years ago|reply
[+] [-] cgravill|8 years ago|reply
(note: I work at MSR, but on other projects)
[+] [-] rmp_|8 years ago|reply
[+] [-] bayesian_horse|8 years ago|reply
[+] [-] JPLeRouzic|8 years ago|reply
Many thanks
[+] [-] unknown|8 years ago|reply
[deleted]
[+] [-] brohee|8 years ago|reply
[+] [-] searine|8 years ago|reply
I've personally used the oxford nanopore to diagnose malaria subtypes from ~1ml blood draws. Though it took awhile to do so, well beyond clinically relevant time periods. Our best turn around was about 2 days for sequence, but analysis takes much longer.
[+] [-] bmcusick|8 years ago|reply
[+] [-] chrisamiller|8 years ago|reply
The enormous reads offer a different window into genomes, by spanning repetitive regions where short reads can't be accurately placed. For lots of applications, the sweet spot is to use long reads for "scaffolding", then build up coverage with short reads.
[+] [-] callesgg|8 years ago|reply
[+] [-] bayesian_horse|8 years ago|reply