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For several years there has been a nerdy debate in some labs about sequencing vs. genotyping (more precisely, doing genotyping-by-sequencing vs. going with an array). There are many pros and cons. If you are working on non-model organisms there may not be a good SNP array for you, so the decision is done. If you work on humans in contrast there are several options which are rather affordable. But at some point I assume that sequencing will get so cheap that that SNP array technology will be rendered obsolete, rather like what RNA-seq is doing to microarrays. Currently the cost of sequencing has not declined much for a few years, as Illumina basically squeezes de facto monopoly allowable price out of customers. At some point in the near future this monopoly will break, with the current bet being on a Nanopore driven disruption of the space. Then the collapse in cost by base genome will commence again, until the technology gets good enough that it’s not really the rate limiter in the pipeline.
With the announcement that 23andMe is increasing their price, from $99 to $199, it got me to thinking about comparing sequencing vs. genotyping. You see, 23andMe uses a SNP-chip. Last I checked just under one million markers, with a custom set of 30,000 added on to the standard Illumina set. They’ve got over one million people genotyped, so they’ve been at this for a long time. But is $199 worth it for a one million markers? As regular readers know I’ve been following the progress of the small start-up Full Genomes for a while. You can get WGS elsewhere, but this group has been very proactive about attempting to cultivate a retail presence (that is, direct-to-consumer). Their prices are on their website, but below is a comparison chart:
| Company | Service | Cost | Time | User-friendly | How much of genome? |
| Full Genomes | 30x coverage | $1,850 | Months | No | Medical grade accuracy of whole genome |
| Full Genomes | 10x coverage | $745 | Months | No | Not medical grade, but probably whole genome |
| Full Genomes | 4x coverage | $375 | Months | No | Will have gaps in genome, but most |
| Full Genomes | 2x coverage | $250 | Months | No | Lots of gaps in genome, but a lot of it |
| 23andMe | 1 million marker SNP | $199 | Weeks | Yes | Accurate genotype calls 1 million out of 5 million variants |
Basically coverage is telling you how many times a marker is going to come back in the raw results. If there an error in one particular position you can figure that out pretty easily if you expect to have sampled it 30 times. In contrast, if you have only one read to look at for a position then if it’s not matching the reference it is highly like you’re seeing a false positive. For evolutionary genomics work low coverage is really not a major issue, because you’re curious about population wide dynamics. But if you want to make accurate calls which are medically actionable, then you need to be confident, and for that you need to have high depth on your coverage. With >30x you’re catching almost all the variants in your genome, and so can pick up things like mutations novel to you, which wouldn’t come back on a SNP-array in most cases, since they’re ascertained on common variants.
Since I knew Full Genomes‘ cost chart I knew that their 2x sequencing is now approaching the genotyping results provided by 23andMe in terms of apples-to-oranges cost comparisons. I say apples-to-oranges, because the truth is that Full Genomes is providing a different service. It’s very much of a “rough cut,” while 23andMe is delivering turn-key personal genomics. But, if you are comfortable with .bam and .vcf files, then now is the time to actually consider sequencing (though from what I know Full Genomes‘ turnaround time is on the order of three to six months, while 23andMe is closer to one month). For me the sweet spot right now would be 10x, as 30x is probably overkill, especially if you already have genotype data and are comfortable with imputation….
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Yes, the Illumina monopoly plateaued prices for years, but that is over. Around last New Year’s they announced wholesale prices of $1000/genome (30x). Which is probably why the retail price you quote is under $2000, a lot less than it was a year ago.
But they’re still a monopoly; it’s not the competition that forced their hand. Maybe they’re expecting a deluge of demand at the new price point, but most people think the magic number is $1000 retail. Maybe they’re ramping up producing in preparation for when they hit that number?
I would pay $1850 for the medical grade sequence if I could do something useful for myself with the information. For example, if a full genome could point to dietary, exercise, or lifestyle changes that would reduce my risk of disease that would be great.
There is also the potential usefulness for mating. That’s already there in limited form with detection of genes that would be harmful if both prospective parents passed them along to their offspring. But it would be much more useful if IQ and other attributes of likely children could be reported.
So Razib, when are we going to get personally actionable information from whole genome sequencing?
The few times I read about an interesting new study on a gene, I used the 23andme lookup feature and every time it was included in their sequence.Replies: @Rick
Re 30x test. I emailed [email protected] with the following:
I can not find a document on your website relating to confidentiality and uses of the results of the test by your company or others. Could you please point me to such a document. Thank you.
they replied that don’t share user’s data with any other organization. (read currently)
They also sent a consent form covering them for legal liability re medical decisions.
I assume there are a lot of sides to the issue: political/legal/medical. I know this thing is in its infancy but these concerns might hold people back.
But it goes w/o saying that whenever you need a SNP-based assay, it’s already cheaper and faster to base it on targeted sequencing than on the arrays, and it’s been so for years, only now Torrent aggressively competes with Illumina on price in this huge market
FWIW, my father recently got a medical grade whole genome done for a medical trial and it took something on the order of 4-6 weeks. It could be that the trial had a particularly efficient work flow for their particular project in place or something, but going from months to a month or two seems like a trend. (It is also possible that it was actually not a whole genome and that he or his treating physician merely misunderstood that detail which wouldn’t have been very salient to them.)
Can’t help but feel kind of bad for 23andme. It’s tough to be first in this market…
Anyways, I’m aware of a startup that’s supposedly going to offer WGS at very subsidized rates — not much more than 23andMe’s new price! They’ll make money by selling your data to researchers but they actually share the bulk of the income with the user. Basically, they’re like an agent for your genome.
I’m wondering, what’s the average amount a researcher would pay for access to a single genome? Would the price vary based on the rarity of present variants? I have absolutely no point of reference for any of this — imagining numbers that range by orders of magnitude.
There is also the potential usefulness for mating. That's already there in limited form with detection of genes that would be harmful if both prospective parents passed them along to their offspring. But it would be much more useful if IQ and other attributes of likely children could be reported.
So Razib, when are we going to get personally actionable information from whole genome sequencing?Replies: @Lot
23andme is focused on the most useful and interesting genes, so for your question of utility, there is not too great an advantage in full genome.
The few times I read about an interesting new study on a gene, I used the 23andme lookup feature and every time it was included in their sequence.
23andme won't tell you that.Replies: @Lot
The few times I read about an interesting new study on a gene, I used the 23andme lookup feature and every time it was included in their sequence.Replies: @Rick
The difference is that a full sequence will tell you about mutations and insertions and deletions unique to you or your family.
23andme won’t tell you that.
My point is that 23andme is cheap and interesting, and the marginal benefit of spending at least 5 times more is very small for the average person. There are a lot of more interesting and fun technologies you can spend your money on and support as an early adopter. How about a top of the line desktop using Intel's brand new Skylake line for $1700? A self balancing scooter for 400?Replies: @Rick
“23andMe’s v4 chip introduced Dec 2013 greatly reduced the number of SNPs (by more than a third) compared to v3. It features just over 602,000 total SNPs instead of the previous version’s 967,000 SNPs.”
http://snpedia.com/index.php/23andMe_v4_differences
23andme won't tell you that.Replies: @Lot
And what does that get you today that is especially useful or interesting?
My point is that 23andme is cheap and interesting, and the marginal benefit of spending at least 5 times more is very small for the average person. There are a lot of more interesting and fun technologies you can spend your money on and support as an early adopter. How about a top of the line desktop using Intel’s brand new Skylake line for $1700? A self balancing scooter for 400?
Just as the simplest case, if you are interested in mutations in the BRCA1 gene that could lead to breast cancer, then genotyping will check for a few common variants. Sequencing, however, will tell you if you have any of the hundreds of described variants, or even a unique one.
Every person also carried inactivating mutations in about 100 genes. They might be important, or explain something about you or your family members' health that hadn't been considered.
Even ancestry will get a huge boost, but not until more people do it. You can find shared rare mutations in otherwise common haplotypes.
Looks like you get what you pay for.
My point is that 23andme is cheap and interesting, and the marginal benefit of spending at least 5 times more is very small for the average person. There are a lot of more interesting and fun technologies you can spend your money on and support as an early adopter. How about a top of the line desktop using Intel's brand new Skylake line for $1700? A self balancing scooter for 400?Replies: @Rick
“And what does that get you today that is especially useful or interesting?”
Just as the simplest case, if you are interested in mutations in the BRCA1 gene that could lead to breast cancer, then genotyping will check for a few common variants. Sequencing, however, will tell you if you have any of the hundreds of described variants, or even a unique one.
Every person also carried inactivating mutations in about 100 genes. They might be important, or explain something about you or your family members’ health that hadn’t been considered.
Even ancestry will get a huge boost, but not until more people do it. You can find shared rare mutations in otherwise common haplotypes.