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Illumina’s HiSeq 2000 Hits $10,000 Genome Mark

Illumina’s new HiSeq 2000 can generate 200 Gb in a single run.

March 16, 2010 | If Illumina’s new HiSeq 2000 proves even half as effective as the invisibility cloak that the San Diego firm deployed before dramatically revealing its existence, then it has a good shot to “redefine the trajectory of sequencing,” as Illumina CEO Jay Flatley told analysts at the JP Morgan Healthcare conference in San Francisco in January. “It is the culmination of the vision we had when we acquired Solexa,” said Flatley. The instrument, priced at $690,000, can generate 200 Gigabases (Gb) in a single run lasting eight days (paired 100 base reads) using dual flow cells. “The output is unprecedented,” said Flatley. He added that the HiSeq is “unmatched in cost effectiveness” and can “drive the cost of a genome under $10,000 and a transcriptome under $200.” Besides human genomes, it could sequence thousands of bacterial genomes simultaneously or unravel 16 transcriptomes in a mere four days.

BGI News

The HiSeq 2000 began shipping in February, with China’s Beijing Genomics Institute (BGI) ordering a staggering 128 instruments—the largest single order for next-gen sequencing systems to date. “The discussions we’ve had over the last few months have been centered on the GA,” said Omead Ostadan, Illumina’s VP marketing. BGI’s decision to switch to the HiSeq 2000 came very soon after Illumina disclosed the instrument.

Genome center managers were afforded previews of the HiSeq just days before Illumina announced the instrument. One staffer requesting anonymity told Bio•IT World that, “It’s going to be very hard for ABI or Complete [Genomics] to counter this move with a 4-5-fold improvement anytime soon.” Some centers might have trouble freeing up millions of dollars of surplus capital for such an unanticipated upgrade.

100 of the 128 HiSeq 2000 instruments will be deployed in Hong Kong, the remaining 28 in Shenzhen, together giving BGI the capacity to sequence about 11,000 human genomes a year. BGI stated it was not its intention to become the largest genome center in the world. The huge HiSeq order simply reflects “calculation about how many projects need to be done at BGI, and that needs over 100 instruments.”

New Standard

The name “HiSeq” was chosen, Ostadan says, because “this platform is going to set a new standard for high-performance sequencing.” The “-2000” suffix is, Ostadan admits, somewhat arbitrary, but made sense given the platform has two flow cells, each with two surfaces.

Illumina has no intention of abandoning the GA, affirmed Ostadan. Illumina also introduced the GA IIe, which will deliver about 40% output of its cousin, priced at just $250,000.

Like the SOLiD platform from Life Technologies, the HiSeq 2000 introduces two flow cells, completely independent of one another. “You can run different applications on both flow cells,” says Ostadan, such as different read lengths, stop/start times, or amount of reagents. The increase in throughput comes from the ingenious ability to image two surfaces of the flow cell using new optics, and Ostadan maintains there remains “tremendous headroom” in the sequence-by-synthesis chemistry.

Customer Compatibility

The new instrument offers some advances in transferring data—files sizes end up being an order of magnitude smaller in size (Gigabytes) but perfectly compatible with any users’ IT architecture around the GA IIx. Ostadan admits that the extended laboratory information management systems (LIMS) capabilities aren’t immediately ready, but stresses the major modifications to the plug-and-play base callers and aligners, variant detectors and visualization tools.

The HiSeq 2000 offers a simplified user interface and touch screen capability, real-time analysis and remote monitoring, which allows users to start a run, go home, and monitor all the quality metrics on their iPhone. The Genome Studio pipeline to process data and call variants is the same. But the quality tables are specific for the HiSeq 2000 base calls. The initial read length spec was set at 2x100 bases. “We don’t believe there’s any reason we can’t extend read length,” said Ostadan.

The drop in reagent costs for human genome sequencing to $10,000 makes it difficult for Illumina to justify a price of $48,000 for its personal genome sequencing service, which debuted last summer. Ostadan says there are no plans to reset the price in the near future, but acknowledged that the price of the sequencing service would come down. “There are number of factors that go into that [price calculation.] There’s a lot other than just the reagents involved in delivering that information,” he said.

This article also appeared in the March-April 2010 issue of Bio-IT World Magazine.
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