A DNA Sequencer Cheap Enough For (Some) Doctors' Offices

cylonlover writes "Until recently, DNA decoding machines — fitting in the US$500,000 to $750,000 price range — would take weeks or even months to sequence a human genome, and the whole procedure would cost $5,000 to $10,000. That could be about to change, however, as Life Technologies introduces the Benchtop Ion Proton Sequencer — a machine that may finally deliver the power of genetics into the hands of ordinary doctors thanks to its $149,000 price tag and ability to decode a human genome in one day at a cost of $1,000."

Comments

Don't believe the hype

[Anonymous Coward]

There are two unfortunate challenges that the Ion Proton approach hasn't yet solved. The first is that the steps required to get the DNA out of human cells and into the sequencer (DNA extraction and especially library preparation) are still frustratingly complex. Their OneTouch device simplifies parts of the library prep but there are still many steps that require highly skilled people doing hours to days of work.
The second major issue is that the genome is being read out in fragments of 200-400 nucleotides, then needs to be assembled. The human genome is full of repetitive regions that are much longer than 200-400nt and when one gets a sequence read from one of these regions, it's can be very difficult to determine which of the copies of the repeat region that sequence came from. Better statistical models and algorithms for genome assembly may solve this to some extent, but there are fundamental limits to what can be done with short sequence reads. Other sequencing technologies don't suffer the short read problem, Pacific Biosciences' hardware for example can read several thousand nucleotide fragments. Mate pairing strategies might be used on the Ion instrument but the library prep for these involves considerably more challenging and manual lab work.

Re:Don't believe the hype

[Samantha Wright]

Pacbio promises a trillion unicorn farts per second. It's hard to take them seriously. As far as medical applications are concerned, the read length in the Ion Torrent system is ten times the size it needs to be, since most (known) diseases occur due to mutations in the very specific and non-repetitive exome, or in its close vicinity. No one (that I know of) has ever seriously proposed using this hardware for de novo sequencing of large eukaryotes, especially since the machine currently on offer doesn't have the well capacity to sequence the whole human genome!

That being said, there's always paired-end reads. I'm guessing the protocol for doing so with this system doesn't exist yet, but they tend to solve most of the repetitiveness problems for shorter read lengths.

Re:Don't believe the hype

[Samantha Wright]

You archive it until you need it. A situation-specific microarray might cost a hundred dollars; those tend to stack up with every hospital visit. With whole exome sequencing like this, you pay the fee once, and have all* the data medical science will ever need about you.

* Not counting repetitive elements, promoter regions, UTRs, spacer DNA, or the epigenome, all of which are known to describe at least a few diseases.

Re:Don't believe the hype

[Anonymous Coward]

The third problem (once you solve the first two) is what the hell you do with all that information. But it's a long way to clinical utility.

Well, if by "long way" you mean five years, then yes, it's a long way.

On the other hand, in five year when this technology gets of the ground, it will transform diagnostic medicine in the same way that the automobile transformed personal transportation.

One huge application is diagnosis of infectious disease. Not only will you know whether what you have is viral or bacterial, if it's bacterial you'll know exactly which antibiotics will work. And you'll probably even be able to correlate you infection with known outbreaks: "There's been 50 other infections with this pathogens in the northeast corner of this city over the last two weeks."

The other huge application is birth defects. Many birth defects are recessive and this technology will tell couple which birth defects they are both carriers for - and could pass on to their children. Also, in the case of most mental retardation, the actual causative mutation isn't known (it doesn't have distinct symptoms) but when the comprehensive databases of human mutations start coming online, it will be possible to know exactly which mutation is causing the problems. And, in rare cases, that will even lead to successful therapy (the other cases will have to wait for general gene therapy).

Bottom line: high throughput sequencing for medical diagnosis is going to be one of major advances of this century.

Re:Hospitals

[Samantha Wright]

Gene hacking already is the next nerd occupation (I should know; I'm in the middle of it. Mozilla even funds projects for it.) Here's one starting place if you're really interested.

About the read/write thing: synthesizing large amounts of DNA from scratch still costs ungodly amounts of money. Further, the ABI IonTorrent system being advertised here is a destructive read; you have to treat a blood sample with a large number of chemicals and then stuff it in a big machine. It's no Star Trek scanner.

Re:Hospitals

[Samantha Wright]

Yes, but it's fraught with errors, and making a single molecule longer than a few thousand bases costs a great deal. A bacterial genome is 0.4-3 million bases; humans are 3.1 billion in total. That's why only the Venter Institute has done it.

Re:Another medical money-grubbing bullshit

[Samantha Wright]

The term "junk DNA" is now only used by shoddy science journalism. We're quite comfortable with how DNA and RNA do what they do. There's a mystery about what happens on the protein side, and the question about what functional bits of RNA (called microRNA) interact with what genes is sheerly a matter of ridiculously obtuse combinatorics. Say whatever else you will about them, fat cancer research budgets have taught us a lot about the essentials.