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.
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).
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.
NextSeq is expensive, but there are cheaper options (from 30k) and you can just send your samples to a sequencing service. I’ve seen costs for a whole human genome at high coverage of between 1 and 3000USD.
Be careful about defining "high coverage" as 30x. Many applications (especially cancer) really require 100x or more to overcome purity and ploidy, or to identify subclonal populations.
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.
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.
> 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 <50bp.
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
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.
I've participated in several large projects that worked to detect SVs from short reads in humans. The results, which remain best of class, are simply disappointing. A tiny fraction of the variants detected were actually resolvable to near-base pair resolution. The vast majority were described in approximate terms, using estimates of breakpoints and allelic structure.
Most structural variation I've seen based on whole genome assemblies is not even classifiable into neat categories like "deletion" or "insertion". If you think that "most" things are detected with short reads then you are deluded by the dominant technology.
"No human genome has ever been completely sequenced" https://news.ycombinator.com/item?id=15534325 There are a lot of gaps where the amount of repetition makes it impossible to reassemble a complete picture from tiny fragments.
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, because it can give answers in minutes.
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.
It's worth noting that those clinical applications were developed when technology didn't allow long reads, so "clinical applications don't need long reads" is at present a truism. There may be potential applications that require long reads that simply couldn't have been invented yet (albeit I haven't the slightest what those would be.)
Yes, but I would say quality is most important in almost all cases. Well, quality being defined as <1% error rate, which isn’t such a high bar.
The most compelling near term applications (NITP etc) use fragmented DNA, and long reads will have no benefit here.
So, yes. Long reads are useful, but you need to have at least reasonable performance in other respects. The same thing has been seen with PacBio, who have not played well in the market, despite having a read length advantage.
How long does it take to get the answer? Even if a big, expensive short read sequencing machine is in the building, it still takes a day or two to reach the necessary data.
The per base error rate is bad. In the case of pacbio, this error process approximates white noise, and so you can deal with it perfectly by increasing read coverage. Things are somewhat complicated with the nanopore tech described in this post, as errors may be correlated due to the way the basecalling is done, but in practice it's nearly as big a problem as you think it is.
For things approaching a read length the per-base error rate of a single read is simply irrelevant. In practice, with sufficient coverage (e.g. 20x) you simply don't care about the per base error rate of the reads.
>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 coverage, and the minion reads for scaffolding.
Can be useful when you’re looking after kids, you’re carrying a child/stuck away from your phone.
I’d guess voice assistance could be useful in other situations too. But for me the error rate still seems too high, and there are limited applications.
The last sentence really stuck home to me (edited for clarity):
While these Red Ocean ideas may not result in creating multibillion dollar companies they do offer opportunity that can lead to riches and personal autonomy.
It’s sad that we live in a world where the goal of personal autonomy is so lofty. We have an over abundance of resources in the West. And yet having the freedom to work on useful things under our own direction is rare. It’s a shame that having “autonomy” is such a difficult goal to obtain.
While is the US is moving slightly backwards... In most of the developed world we have never had as much free time, vacation and money as we do now.
You don't need to have your own business to have some degree of personal autonomy. In many ways you'll have fewer responsibilities if you're just an employee, and a larger degree of self-determination.
I'm not necessarily convinced doing your own business is a guide to happiness. That said, author has a point, if you do want to try, maybe avoid VC money. It's easier to become profitable if you're not dragged down by investors who needs to profit first.
You're underestimating how expensive that goal is. Providing every adult with basic income so that they can pursue their dreams would bankrupt the country.
I’m not really talking about providing a basic income.
What I’m saying is the barrier to having “personal autonomy” in a society where providing the essentials of life has to a high degree already been automated, is too high.
Work for a year then take two years off? Or retire earlier? Again, I didn’t say that people wouldn’t work at all. I said that the barrier to obtaining a personal autonomy is too high in a society where providing the essentials of life has been largely automated.
We keep people working by making it had to survive otherwise (high rents that don’t represent the maintainence/construction costs etc).
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.