14 March 2013

NGS Year in Review Part 1: Promises, Promises

In an annual ritual, the various NGS vendors gathered in Marco Island at AGBT to sell their wares and tout their technology to the eager attendees. I figured this makes it a good time to review what's happened over the past year. I’ll start by covering which promises were kept and which were broken, and follow up with subsequent posts on a more general overview of the progress we’ve seen, another one on the mergers that did and didn’t happen, and finish up with a post where I take a stab at what we'll see over the coming year.

2012 was a year of hope and promises. The NGS market is brutally competitive, with all the vendors trying to outdo each other, and 2012 was no exception. The major cycle of announcements that gives us a hint at what we were to see in the upcoming year starts with the JPMorgan Healthcare Conference and finishes with AGBT on Marco Island. 

Last year Ion Torrent (Life Technologies) kicked everything off by announcing their new machine, the Proton. While many, myself included, groused that this new machine made a mockery of their slogan 'The chip is the machine', it was necessary for them to keep pace with their previous promise of improving outputs 10-fold every 6 months. The first Proton chip, the PI, was slated for mid-2012 and would generate 10Gb/run. Not bad, but it was the following PII chip, slated for the end of 2012, that caught everyone's attention. If it were to keep up the trend of 10-fold improvements, it would generate 100Gb of data in a few hours. Better yet, it would finally achieve the holy grail of NGS - the $1000 genome! But Ion Torrent didn’t quite pull it off. Despite making progress, their schedule has started to slip and the output specs are starting to look more meager. Combined, it means they didn’t hit the fabled $1000 genome in a day. Not even close. By the end of 2012 (and through AGBT 2013), their most advanced commercially available chip, the PI, generates around 10Gb of output per run. At $1000 per chip, it would cost around $9k and take up to a week to sequence a human genome. Getting better, but still not there. The chip they said would reach the goal, the PII, was first delayed to March 2013 and now to ‘mid-2013’. Also, rather than generating 100Gb at launch, they’re now talking about 32Gb/run at launch, climbing to 64Gb over time (probably about 12 months). So we might not see the “$1000 genome in a day” from Ion Torrent until mid-2014, or even a bit later.

Illumina got much closer to fulfilling their promises, but that’s partially because they weren’t so bold. While they did claim they’d have the ‘genome in a day’ by the end of 2012, they never said anything about what it would cost. The machine to perform this trick, the HiSeq 2500, was released and the official specs at the end of 2012 were pretty close – 27 hours for a 30X genome (90Gb). With recent improvements (especially on sample prep and analysis), they should be able to go from DNA to analyzed sequence in under 24 hours.

Ion Torrent and Illumina made their big announcements at the JP Morgan Healthcare conference, but Oxford Nanopore (ONT) saved their news for the more scientifically oriented AGBT meeting. And by all accounts, their short presentation stole the show and set Twitter afire. While they had already given us a peak at their upcoming GridION system, they started putting some specific numbers behind it, with the most dramatic being a 20-node system that by 2013 would sequence a genome in 15 min for ~$1000 ($10/Gb). Oh, and they gave a peak at some really intriguing data – 50kb reads with a 4% error rate (that would drop to 1% by the launch). But then they really stirred things up when they unveiled the MinION, a disposable handheld nanopore sequencer the size of a large USB stick, suitable for field work (including no need for sample prep), that would cost under $900 and generate over 1Gb of data. And both the GridION and MinION would launch in 2012.  Nanopores were finally here! These claims were met with incredible excitement and even appeared to shake up the emerging NGS space by, allegedly, prompting Halcyon Molecular to close up shop.
Almost immediately, however, the cries of “Show me the data!” started to emerge from the ranks of scientists. As mid 2012 approached with no new data, the shouts became stronger. Some, myself included, held out hope when ONT was scheduled to appear at ASHG. A booth with pretty but non-functional demo units was all we got – still no data. When the agenda for AGBT 2013 came out, ONT was nowhere to be seen, so any hope of a last minute nanopore miracle vanished. But ONT did attend the show, and CTO Clive Brown gave an impromptu interview to noted blogger Nick Loman that seemed to reveal some of the issues that they were running into and a maybe/sorta indication of a 2013 launch (or at least data from early access customers). While many feel burned by ONT's undelivered promises, the truth is that all will be forgiven once they get their hands on a functioning nanopore sequencer. Book your tickets now for AGBT 2014. 

[If you’d rather listen to me speak than read my words, Theral Timpson interviewed me about this over at Mendelspod.com]