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Nanopore MinION – $1k solid-state DNA sequencers

nanoporetech.com

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

#91

Post by bayesian_horse »

sdcuevas wrote: post #84
eggie wrote: post #63

Earlier quoted context omitted.

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.

Let's assume the company statements are true, they are shipping on time; what is the break even point for shipping $1,000 starter kits, flow cells, and sample prep items? How many devices are they shipping? What's their revenue? https://www.investopedia.com/terms/b/breakevenanalysis.asp Are they anywhere near break even or are they going to require another large infusion of venture capital and can Nanopore find these…

Their sales data is not available. The MinION program does not seem to be designed to finance the company, though it might actually be profitable. The PromethION on the other hand, is selling faster than they can ship the devices.

Their valuation is not about short term sales. Their technology really is somewhat of a holy grail. There is no "simpler" way to read DNA in terms of technology. Everything else involves complicated biochemistry. Illumina beats Nanopore Technologies right now because of the scale of their machines. But they can't scale them down much further without losing performance. The most efficient Illumina machines will always be cupboards or bigger.

No competitor can come up with something better than ONT. Nothing smaller, for certain. The only way to beat Oxford Nanopore in the future will be to implement a very similar nanopore sequencing scheme.

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

#92

Post by comstock »

bayesian_horse wrote: post #91
sdcuevas wrote: post #84

Earlier quoted context omitted.

Let's assume the company statements are true, they are shipping on time; what is the break even point for shipping $1,000 starter kits, flow cells, and sample prep items? How many devices are they shipping? What's their revenue? https://www.investopedia.com/terms/b/breakevenanalysis.asp Are they anywhere near break even or are they going to require another large infusion of venture capital and can Nanopore find these…

Their sales data is not available. The MinION program does not seem to be designed to finance the company, though it might actually be profitable. The PromethION on the other hand, is selling faster than they can ship the devices. Their valuation is not about short term sales. Their technology really is somewhat of a holy grail. There is no "simpler" way to read DNA in terms of technology. Everything else involves co…

The accounts of all UK companies are filed publicly. They had about 1M GBP of sales in 2016 from memory. I would guess with overheads, each unit is currently sold at a loss.

Illumina doesn’t beat nanopore because of the “scale” it beats it because the technology produces fundamentally higher accuracy data. The error rate on Nanopore reads is >10%. Even on first generation Illumina machines the error rate was 1%, and is now significantly lower.

Oxford Nanopore have been working on this for 15 years, this is the best they can do. It might be possible to create a Nanopore (maybe solid state, not protein) system with a lower error rate, but I think they have little hope of doing it.

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

#93

Post by aroch »

burfog wrote: post #25
aFLH7U2daj wrote: post #12

Earlier quoted context omitted.

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…

If you want to do a human or a dozen related humans, and then discard the equipment, is there anything cheaper? That is, without handing the DNA over to somebody else.

A MiniSeq or MiSeq would be cheaper by the time you do the 3 flow cell/person (minimum -- they claim 10-20GB/flow cell but that's bullshit -- so at least ~4K, probably closer to $8k of chemistry/person). You can get a used MiSeq and for ~$50k then its ~1500/person

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

#94

Post by comstock »

bayesian_horse wrote: post #56
sdcuevas wrote: post #54

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.

I would guess they currently make a loss on every device shipped. Most current sales are about generating press coverage/traction, not revenue.

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

#95

Post by comstock »

eggie wrote: post #63
sdcuevas wrote: post #54

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...

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.

I think they like to say they have a patent monopoly, but I don’t believe they do. Genia (which also has issues) are developing a protein nanopore platform.

Illumina (see recent IP battle with Oxford Nanopore) also have key IP in this space (for mspA).

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

#96

Post by comstock »

sdcuevas wrote: post #84
eggie wrote: post #63

Earlier quoted context omitted.

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.

Let's assume the company statements are true, they are shipping on time; what is the break even point for shipping $1,000 starter kits, flow cells, and sample prep items? How many devices are they shipping? What's their revenue? https://www.investopedia.com/terms/b/breakevenanalysis.asp Are they anywhere near break even or are they going to require another large infusion of venture capital and can Nanopore find these…

They’re going to need more money.

I think they’d need to sell >10,000 units a month. That is if they are making any kind of profit. Unfortunately I don’t think there’s a market for anything like that number of flow cells.

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

#97

Post by daemonk »

burfog wrote: post #25
aFLH7U2daj wrote: post #12

Earlier quoted context omitted.

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…

If you want to do a human or a dozen related humans, and then discard the equipment, is there anything cheaper? That is, without handing the DNA over to somebody else.

If you want to do absolutely everything yourself from DNA extraction to sequencing and data analysis, then yes, this is probably the cheapest way.

But you also need to consider how you prepare your DNA to go into the Nanopore. It's a lot more investment than you might think. Extracting your DNA in a clean enough way for it to work with the Nanopore will require equipment/facilities that most people will not have access to (phenol/chloroform is the optimal way to extract DNA, which will require a fume hood and toxic chemical disposal). Depending on how you want to prep your DNA, you might need more specialized equipment/reagents (Ampure beads, ligation kits, end-prep/TA-tailing, etc).

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

#98

Post by rotexo »

daemonk wrote: post #90
rotexo wrote: post #76

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 Oxfo…

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…

The computational barriers are definitely an issue. I thought I had read rumors on twitter that ONT was trying to implement read-until on one of their larger-scale sequencers (one of the ones with compute integrated).

Barring that, the Cas9-mediated targeting method looks somewhat promising (https://www.youtube.com/watch?v=DGDH-FdoARM). No need for amplification! Though for applications with human DNA you might run into some issues with the copy number of a sequence of interest if you’re starting out with a normal amount of genomic DNA.

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

#99

Post by comstock »

bayesian_horse wrote: post #85
comstock wrote: post #53

Earlier quoted context omitted.

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?

Virtually all applications can benefit from long reads. There are already hybrid assemblers out there which take Illumina, Pacbio and Nanopore reads. The long reads tie the short reads together, whereas the short reads improve the accuracy. The area where DNA sequencing will first be revolutionizing clinical practice is in sequencing pathogens for sake of identification. In these instances nanopore sequencing rules,…

Most clinical applications don’t need long reads. Pathogen identification from short reads is easy. Blood tests for cancer, and NIPT (which will likely be the first big applications) both use fragmented DNA in the blood, so long reads are not useful. Depth (lots of sequencing) and quality are far more important.

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

#100

Post by comstock »

searine wrote: post #71
comstock wrote: post #35

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…

>The error rate is stupidly high (somewhere between 10 and 20%) The Insertion/deletion error rate is 20-30%. The point mutation error rate is something 0.1-1% (higher than HiSeq but not crazy high). This means with a semi-decent reference genome you should be able to do re-sequencing fairly accurately. It also means, that in conjunction with HiSeq reads you can do cheap genome assembly, using the HiSeq reads for cove…

Do you have a citation for this? Because this is not my understanding.
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