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]
