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Illumina to Launch Sequencing Module for iScan this Year; Other Techs in the Works

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As it continues to upgrade its existing Genome Analyzer platform, Illumina is developing new products and technologies for the $1.1 billion dollar sequencing market, which it estimates will grow to $1.5 billion by 2011.

"We are really excited about what's happening in the sequencing market," said Illumina President and CEO Jay Flatley in a presentation at the JPMorgan Healthcare Conference in San Francisco last week. "We think over the next few years, it's going to be the most exciting segment in life sciences tools, so we continue to make major investments in this space."

The company plans to launch a sequencing add-on module, called Harmonia, for its iScan genotyping platform in the second half of this year that targets Illumina's genotyping customers who want to give sequencing a try, according to Flatley.

Harmonia, which appears to be a stripped-down version of the Genome Analyzer, is expected to have between 10 and 20 percent of the throughput of the GA and represents an "inexpensive, low-risk way for array users to enter into now generation sequencing," according to Flatley's presentation.

Flatley said the module, which will be designed to scan BeadChips and sequencing flow cells, will be a "great transition product" that targets customers wanting to perform targeted resequencing studies to follow up on results from genome-wide association studies. Other customers would be those who want to migrate applications, such as gene expression analysis, from arrays to sequencing. He did not reveal the price of the product.

He also mentioned the Avantome sequencing technology, which Illumina acquired last year but did not reveal any specfic commercialization plans last week. "Avantome, we think, is going to become a very important product for us, one that targets very rapid sequencing and long, Sanger-range read length," he said.

Hedging its bets for future sequencing technologies, Illumina made an $18 million investment in UK-based startup Oxford Nanopore Technologies, a move it disclosed last week. Oxford's nanopore sequencing technology "holds tremendous promise to be one of the first technologies to reach the sub-$1,000 genome and become the cheapest and fastest way to sequence DNA," Flatley said during his presentation (see In Sequence 1/13/2009).

Illumina has also been working to improve its existing Genome Analyzer platform, which at the end of 2008 was capable of generating up to 3 gigabases of sequence data per day, based on paired-end reads of 100 base pairs each, a 51-minute cycle time, and 13 million clusters per lane, said Flatley.

This represents a 15-time improvement in output per run over the beginning of 2008, Flatley said, while the throughput has increased about threefold since early 2008, when it was 1.2 gigabases per day.

The most important recently launched applications are a sample multiplexing capability and a mate pair library prep kit, he said.

The sample multiplexing application lets users attach DNA barcodes to fragment libraries during the sample prep step, so they can sequence eight samples per lane, or 96 samples per flow cell, in the same run.

The mate pair library prep kit enables users to generate paired-end reads with inserts ranging from 2 kilobases to 10 kilobases in size. "This allows very large-range structural analysis of the genome, and this hasn't been possible on the Genome Analyzer until just recently," Flatley commented.

Enabled by the longer paired-end reads, the Genome Analyzer is now starting to be used for de novo genome sequencing projects, Flatley said, for example of bacterial and fungal genomes and of organisms important for agricultural research, "because we have tremendous cost advantages over alternative approaches."

Illumina competes in this area with Roche's 454 Life Sciences, whose Genome Sequencer FLX produces longer reads at a higher cost per base.

Flatley specifically mentioned a recent project in which researchers at the Beijing Genomics Institute in Shenzhen sequenced the panda genome, representing "the sequencing of the first mammalian genome de novo on our system."

For this project, which has yet to be published in a peer-reviewed journal, the researchers generated 150 gigabases of sequence data from 75-base pair paired-end reads and covered 95 percent of the panda's gene regions, according to Flatley (see also In Sequence 12/2/2009).

In addition to entering de novo sequencing, the Genome Analyzer is also increasingly displacing array-based and other methods, for example in ChIP-sequencing, digital gene expression analysis, and methylation sequencing, he said. "We are seeing application convergence from arrays and other technologies onto next-gen sequencing."

Sequencing is now driving a number of large-scale research projects, Flatley said, in which the Genome Analyzer plays a role. These include the 1,000 Genomes Project, the International Cancer Genome Consortium, and the Human Microbiome Project.

The 1000 Genomes Project has already generated 1,500 gigbases of sequence data in its pilot phase, he said, "the vast majority of which was generated and deposited from the Genome Analyzer."

Later this year, Illumina hopes to use rare sequence variants that were uncovered in the 1000 Genomes Project as content for new array products, he added.

Sequencing has already generated content for several new array products, two of which Illumina launched this month: the PorcineSNP60 BeadChip, which derives 65 percent of its content from the Genome Analyzer, and the OvineSNP50 BeadChip, which receives 30 percent of its content from the platform, he said.

According to Flatley, the Genome Analyzer continues to be adopted by users outside of genome centers. Seventy-five percent of Genome Analyzer sales went to non-genome center customers during the fourth quarter of 2008, and 85 percent in all of 2008.

As the Genome Analyzer finds wider applications and enters more labs, the cost of sequencing continues to decline, Flatley said, with pricing showing "dramatic elasticity."

"This is going to be very similar to what happened in whole-genome genotyping a few years ago: as prices go down, the number of samples that are going to be sequenced is going to go up rapidly," he said.

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