Wednesday, 29 February 2012

Illumina: Aces in the hole?

The past two weeks have seen Oxford Nanopore reclaim the title of most talked-about sequencing technology and the wake of hyperbole, hope and suspicion left behind by the announcement that their GridION and MinION systems will be available this year has done some damage to the field's biggest players - Illumina and Life.

Not only did the announcement of the Oxford bred technology cause the dropping of many a scientist's jaw but it also led to 3.9 percent and 7.8 percent drops in share prices for Illumina and Life respectively.  The Web is awash with questions of what effect nanopore technology will have on the field as a whole but whilst the world awaits something tangible from Oxford Nanopore, let us not forget that Life and Illumina have each made some major announcements in early 2012.

Old toys improved
Illumina announced significant improvements to their desktop MiSeq system in the form of lower runtimes, 250bp paired-end reads, and a dramatic increase in throughput to 7GB per run.  Many had believed that the system's potential for improvement over release specs was limited but these announcements suggested the opposite.  James Hadfield at CRUK has even questioned if the system will in fact prove scalable to the level of human genome sequencing.

Life meanwhile released their 318 chip and its nominal 1GB output was quickly exceeded with internal data runs exceeding 2GB.  Meanwhile, throughput on the smaller 314 and 316 chips continued to increase at an even greater pace.  Plans to launch 2x200bp paired end reads and 400bp single end reads in 2012 were also announced at an AGBT meeting where Life's inventive marketing was impossible to escape.

Perhaps the biggest announcements however came in the form of...

Sparkly new toys

January saw Life's announcement of the Ion Torrent Proton, a $149,000 benchtop analyzer estimated to ship to early access customers in mid-2012 coupled with the Ion Proton I chip - said to be ideal for sequencing human exomes.  Human genome sequencing was predicted to come to Ion Torrent by 2013 with the Ion Proton II chip promising the holy grail of human genome sequencing for $1000, and in a day.

Illumina returned fire the same day by press releasing their HiSeq 2500 system which similarly promised the ability to sequence a human genome in a day (120Gb in 27 hours) but with a hefty $740,000 price tag or $50,000 as a field upgrade to the HiSeq 2000.  Full commercialization of the new system is expected in the second half of this year.

Consumer opinions
Regardless of the fact that each set of announcements could be argued to be equally important or advantageous, the buzz seems to have surrounded Ion Torrent.  Major acquisitions of Illumina sequencers have continued however there seems to be an increasing attitude of indifference and even caution directed at the Illumina technology despite its proven utility and ability.

One online poll shows only 50 percent of correspondents believing that purchase of Illumina technology is still a good idea with 25 percent classifying such purchases as 'very risky'.

These changing attitudes are no doubt partially due to our love of new toys and a superior marketing campaign by Ion Torrent, however less fickle motives also exist.

Illumina beaters

Currently, the PGM offers greater flexibility in terms of run-size.  The existence of the 314, 316 and 318 chips offers the user a level of control over run-size and cost that cannot be achieved on MiSeq.  The announcement of the Proton I and II chips would suggest that this advantage will translate to the higher-throughput sequencing, potentially threatening future HiSeq purchases.

The announcement of the Proton has shown us all that the chip is not necessarily the machine after all however the increases in throughput achieved on Ion Torrent technology have been impressive and there is a belief that this will continue to bring future improvements and advantages long after Illumina chemistry has hit its ceiling.

Both the PGM ($50k vs $125k for MiSeq) and Proton ($149k vs $740k for HiSeq 2500) are priced well below their Illumina-based counterparts.  These prices are based on sequencer only but the numbers speak for themselves.  There have also been reports of Life being more willing to negotiate on cost, despite lower list prices.

There is a growing belief that Life will continue to be the winner in these important areas and that Illumina represents the technology of yesterday.

Surprises in store?
Is this really the case though?  Or do those who write off Illumina as an old man playing a young man's game risk a shock?  Beyond January's announcements could Illumina have something else up their sleeve?

Whilst travelling home from AGBT, on the bus to the airport I had the pleasure of meeting Dan Koboldt who described speaking to a casually confident Jay Flatley during the meeting.  I can personally say that while the buzz at AGBT may have been around Life (and later Oxford Nanopore), Illumina were far from silent.

Talks and posters made it clear that Illumina is still the big player in the market, being used widely in traditional as well as increasingly clinical applications.  Roche's interest in the technology speaks volumes about its perceived clinical utility.

In and around the elegant Illumina lounge between distribution of drinks and genomes on USB sticks there were whisperings of potential new products.  There was talk of new kits that would add greater flexibility to run-size and cost.  Also, there were suggestions of entirely new sequencing technologies arriving within the calendar year.

Whilst the Oxford Nanopore announcement raised questions about the future of the field and the price of shares, it also raised another: how will Illumina's relationship with the company and its exonuclease sequencing technology  manifest in the market?  Beyond that how will it align with Illumina and Oxford Nanopore's other hardware offerings?

There is no doubt that Illumina's position is being increasingly challenged by the emergence of new, innovative technologies but the status of market leader was not achieved by accident.  The prowess that achieved sequencing dominance could still surprise the challengers with a reappearance.

In this market nothing is certain but I won't be writing off Illumina just yet.


  1. Hello Gavin.

    Very insightfull.

    Thanks. Best regards.


  2. Thanks a lot Ezequiel - comment appreciated!