Thursday, December 18, 2008
You gotta love the breakneck speed at which whole genome sequencing is proceeding. Hell, by the end of 2010 we will have a complete genome for 1000. But the big rub is......how accurate will it be?
I was just telling a partner at Burrill and Company about how the whole field of genetic esoteric testing goes out the window when you can have a genome for 1000 USD. But what I didn't say was, "That's assuming the data is valid"
You see, we can be pretty accurate when sequencing a gene or 2. But when it comes to whole genome sequencing the best these companies can get is 95% correct. So I say, what's 5% between friends..........For clarity, this is per read according to some companies. But I maintain that even with 30x coverage, you will still have too much error to trust this, at least when it comes to making healthcare decisions....
I say this in response to the "pinheads" selling SNP scans DTC and "claiming that they hold the keys to all disease.....That 0.1% difference is not all that matters, in fact I would guess it is merely one of approximately 7 or 8 factors that play heavily into common human disease.....That's why the SNP Chip companies dropped prices and may have destroyed the commercial market for this test....Slide pic brought to you by Andrew....Thanks Drew!
In fact, that is precisely why Coriell will be tremendously successful at recruiting volunteers for their study. People realize 2500 USD is not the cost of a 1 million SNP can, in fact by the end of the year it may very well be the cost of a complete genome....
But here's the question...how is the accuracy of that "Discount DNA" to quote the author David Ewing Duncan......
We know that Helicos actually kept their error rate quiet for some time. But then
"Initial commercial specifications for the Helicos™ Genetic Analysis Platform were set at 50 Mb per hour; 10 Gb per run in 8 days. Early adopters can expect 8 million reads at length-of-read from 25 to 50 bases in each of the 50 flow cell channels utilized, totaling 400 million reads per run. Aftermarket costs are approximately $1.80 per megabase sequenced or $45 per million reads. Additionally, performance is independent of template sizes anywhere from 25 b to 8 Kb. The total error rate is less than or equal to 5%, with a competitive 0.5% substitution error rate. Further, the error rate is independent of the read length. The HeliScope Sequencer is capable of accurately sequencing samples with 20% to 80% GC content. "
The dirty truth..........Yes, now those SNP scans are looking a heck of a lot more accurate than the wonderful complete genomes we may have....Hmmmmm...can some one do the math for me.....what's 5% of 3 billion? What about 6 billion? Even if not that high, what is 0.1%....isn't that what the SNP companies tell you can cause "all disease???"
Uh-Oh.....we may have a complete genome for 2500 USD, but whose genome is it? 0.1% makes us different, right? This problem will hamper the entire field for quite some time. Imagine all the false positive data that may be generated here. If you think GWAS needed replication, wait until you see W-GWAS studies. We are going to have so much false positive data out there until we can perfect the technology...I can't wait to see the next level of commercial ventures to arise prematurely from Complete Genomics....Have they said their error rate? I have a big problem with any company who says "Don't do the sequencing....we'll do the sequencing and give you the data.
In fact, there is a guy on house arrest in Manhattan for doing a similar thing. His name is Madoff. He said "I have a secret formula, trust me, I can give you fantastic returns.....Until my kids turn me in"
I wonder if Complete Genomics is the Genome's Ponzi scheme. I wouldn't assume so, since George Church is on their board and if anyone is a purist it's him. But hey, how will anyone know that without "double checking" the books???? Even if they have a dramatically lower error rate than Helicos.......
Unless the error rate gets to about 0.001% then we may have to wait a while before we can do most meaningful things with the "Whole Genome and nothing but the Genome"
The Sherpa Says: My take, we need to study how SNP scans AND whole genome scans may affect healthcare outcomes. If we aren't answering questions for clinicians and the public what are we doing? Providing neat websites based on false or lackluster data? We have to be serious here and figure what it all means before we start using this. That's precisely why 23andMe says that there scan shouldn't be used for healthcare....because they too know it is not ready for prime time.....I wonder how Complete Genomics feels about that? Because, I for one am a little concerned about the whole "black box" technology movement and applying it to my patients' care. But it is pretty obvious MDVIP doesn't care.
Posted by Steve Murphy MD at 5:59 AM