IT LOOKS like an ordinary USB memory stick, but a little gadget that can sequence DNA while plugged into your laptop could have far-reaching effects on medicine and genetic research.
The UK company Oxford Nanopore Technologies built the device, called MinION, and claims it can sequence simple genomes 鈥� such as those of some viruses and bacteria 鈥� in a matter of seconds.
More complex genomes might not be practical at first, but MinION could also be useful for quickly sequencing DNA from cells in a biopsy to look for cancer, for example, or to determine the genetic identity of bone fragments at an archaeological site.
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MinION has already sequenced a simple virus called Phi X, which contains 5000 genetic base pairs, the company announced last week at the Advances in Genome Biology and Technology (AGBT) conference in Marco Island, Florida.
This was done as a proof of principle. 鈥淧hi X was the first genome ever to be sequenced,鈥� says Nick Loman, a bioinformatician with the Pallen research group at the University of Birmingham, UK, and author of the blog Pathogens: Genes and Genomes. It shows the technology works, he says. 鈥淚f you can sequence this genome you should be able to sequence larger genomes.鈥�
Oxford Nanopore is also building a larger device, called GridION, for lab use. Both GridION and MinION operate using the same technology: DNA is added to a solution containing enzymes that bind to the end of each strand. When a current is applied across the solution these enzymes and DNA are drawn to hundreds of wells in a membrane at the bottom of the solution, each just 10 micrometres across.
Within each well is a modified version of the protein alpha hemolysin (AHL), which has a hollow tube just 10 nanometres wide at its core (see diagram). As the DNA is drawn down towards to the protein, the enzyme attaches itself to the AHL and begins to unzip the DNA, threading one strand of the double helix through the pore.
Each of the four bases along a DNA strand has unique electrical characteristics, and each disrupts the current flowing through the pore in a slightly different way. This is enough to determine which of the four bases is passing through at any one time. Each disruption is read by the device, like a ticker-tape reader.
This approach has two key advantages over other sequencing techniques: first, the DNA does not need to be amplified 鈥� a time-consuming process that replicates the DNA in a sample to make it abundant enough to make a reliable measurement.
Second, the devices can sequence DNA strands as long as 10,000 bases continuously, whereas most other techniques require the DNA to be sheared into smaller fragments of at most a few hundred bases. Once they have been read, the results have to be painstakingly reassembled by software like pieces of a jigsaw. 鈥淲e just read the entire thing in one go,鈥� says Clive Brown, Oxford Nanopore鈥檚 chief technology officer.
鈥淚 think this is the most exciting news in DNA sequencing for a long time,鈥� says geneticist and blogger Daniel MacArthur.
Oxford Nanopore is set to face stiff competition, however. Jonathan Rothberg, a scientist and entrepreneur who founded rival firm 454 Life Sciences, also announced at the AGBT conference that his start-up company, Ion Torrent, will be launching a desktop sequencing machine. The Ion Proton identifies bases by using transistors to detect hydrogen ions as they are given off during the polymerisation of DNA.
This device will be capable of sequencing a human genome in 2 hours for around $1000, Rothberg claims. Nanopores are an 鈥渆legant鈥� technology, he says, but Ion Torrent already has a foot in the door. 鈥淎s we saw last summer with the E. coli outbreak in Germany, people are already using it,鈥� he says.
The GridION will take several hours to complete a human genome, by contrast. The MinION, while not designed for full human genome sequencing, will be marketed for use in shorter sequencing tasks like identifying pathogens, or screening for genetic mutations that can increase risk of certain diseases. Each MinION is expected to cost $900 when it goes on sale later this year.
鈥淭he biggest strength of nanopore sequencing is that it generates very long reads, which has been a limitation for most other technologies,鈥� says Loman.
As for clinical applications, David Rasko at the Institute for Genome Sciences at the University of Maryland in Baltimore, says the MinION could have huge benefits. 鈥淚t may have serious implications for public health and it could really change the way we do medicine,鈥� he says. 鈥淵ou can see every physician walking around the hospital with a pocketful of these things.鈥� It is likely to increase the number of scientists generating sequencing data, he adds.
Correction: When the article first appeared, it stated that the MinION could completely sequence a human genome in 6 hours, and that a GridION could do it in 15 minutes. This is incorrect 鈥� a single MinION cannot complete a human genome, and a single GridION would take several hours. The article has been amended to reflect this.
鈥淭his could change the way we do medicine. You could see every doctor walking around with these things鈥�
