domingo, 16 de febrero de 2014

Oxford Nanopore unveils data from portable genome sequencer

MinION results are promising, but fall short of high expectations.

Oxford Nanopore

Oxford Nanopore's MinION sequencer can read DNA fragments up to 10 kilobases long.

A good first shot, but not a game-changer — yet. That seems to be the consensus among scientists after the first public release today of data produced by the MinION, an advanced and much-anticipated DNA sequencing device developed by Oxford Nanopore in the UK.

The MinION aims to be the first commercially available sequencer that uses nanopore technology, which has been in development for nearly two decades. The approach identifies bases of DNA by measuring the changes in electrical conductivity they generated as they pass through a biological pore. Oxford claims that its nanopore machines will be faster and cheaper than existing sequencing technologies, and will allow scientists to analyse regions of the genome that cannot be amplied.

The MinION is not yet for sale. But David Jaffe, a computational biologist at the Broad Institute in Cambridge, Massachusetts, used data produced by the device and provided by Oxford to aid in the assembly of two bacterial genomes — those of Escherichia coli and a bacterium from the genus Scardovia that is found in the human mouth. He presented his results today at the Advances in Genome Biology and Technology meeting in Marco Island, Florida.

It’s kind of a cute device,” Jaffe says of the MinION, which is roughly the size and shape of a pack of gum. “It has pretty lights and a fan that hums pleasantly, and plugs into a USB drive.” But his technical review is mixed.

The average length of the sequences generated on the MinION was 5.4 kilobases, with some as long as 10 kilobases. That is longer than the average read delivered by the current dominant technology, sold by San Diego, California-based Illumina, which delivers fragments of DNA that are hundreds of base pairs long. But the median length of the MinION’s reads is shorter than the target that Oxford announced in 2012.

Mixed picture
Jaffe also found that the MinION appeared to have difficulty sequencing particular parts of the bacterial genomes that he studied. That is worrisome to bioinformaticians, because it is more challenging to correct for systematic sequencing errors than random ones. In Jaffe's case, the recurring errors prevented him from assembling the complete genome sequences of the two bacteria from scratch using only MinION data; instead, he used MinION sequences to supplement data generated by Illumina machines.

Yet he sounded an optimistic note about the MinION's future. Oxford has said that higher-quality DNA or different preparation methods should increase the average read length. Jaffe says that the company can work to eliminate errors, perhaps by using a mix of pores with different properties. But even now, he says, the vast majority of long MinION reads had lengthy stretches without any mistakes. The systematic errors are “a temporary feature that we hope they'll figure out how to solve.

Other researchers will soon have a chance to form their own opinions about the new device, as Oxford today launched its early-access programme. Researchers who pay a US$1000 deposit, plus $250 for shipping costs, can receive MinIONs on which they can run their own experiments.

Isaac Ro, an analyst at the investment bank Goldman Sachs — which advised Illumina in 2012 when it fought off a takeover bid by the drug giant Roche — called Jaffe's presentation “underwhelming”. “Oxford Nanopore still appears to be in development mode and, in our view, is unlikely to threaten [Illumina’s] competitive position at this time,” he said in a research note.

But some scientists still think that the MinION has potential to shake up the sequencing industry. Geneticist Yaniv Erlich of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, says that the small, cheap and portable MinION is unlike the bulky, pricey sequencing machines that scientists are used to. If Oxford continues to improve the technology, he says, it will enable a range of applications that are not possible today, such as using sequencers in the field.

This reminds me of the early days of Illumina, when all we could get were 36-base-pair reads, and we were all very excited about that,” Erlich says. “I think we should give [Oxford] more time.
Nature doi:10.1038/nature.2014.14724

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By Erika Check Hayden
14 February 2014 

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