By Monica Heger
This story has been updated from a version published Feb. 17 to correct pricing information.
Illumina has launched a cancer genome sequencing service that will incorporate an "optimized combined caller method" for improved accuracy of variant calls in heterogenous tumor samples.
For $14,000 the company will provide whole-genome sequencing of a matched tumor/normal pair at 80-fold and 40-fold coverage, respectively, as well as basic analysis. Discounts will be provided for larger orders and transcriptome and epigenome sequencing can also be ordered as add-on services.
Turnaround time will be about 10 weeks from the time the sample is received for up to 100 genomes.
According to Tanya Boyaniwsky, Illumina's senior market manager of genomic services, the company will initially offer the service through its research lab and its partners in the Illumina Genome Network. It plans to eventually move the service into its CLIA certified laboratory, but did not provide a timeline.
"Our goal is to verify and put together a robust protocol and technology and then transfer over to the CLIA lab when it's ready," she said.
Currently, the service is performed on the HiSeq 2000. However, it is "perfectly amenable for the [HiSeq] 2500," and will eventually be offered on that platform as well, Boyaniwsky told Clinical Sequencing News. The company has targeted a mid-year launch for the HiSeq 2500, which will have the capability to sequence a human genome to 30x coverage in a day, and has already started using it internally for its sequencing services business.
Illumina will use its TruSeq reagents for sequencing and will also do array-based genotyping to allow researchers to further validate and compare results across technologies.
All sequencing data, including both aligned and non-aligned reads, will be returned in archival BAM format to enable researchers to work with third parties for further analysis. Illumina will also return results of its own analysis, including all variant information on SNPs, indels, large insertions and deletions. It will also provide a summary report of the variants that displays the somatic calls graphically, Boyaniwsky said.
The new service further positions the company as a direct competitor to Complete Genomics, which launched a cancer-specific sequencing service last year (CSN 10/12/2011). Complete charges $12,000 for a tumor/normal sample at 80-fold coverage each, and $18,000 for a trio, such as a tumor, metastasis, and normal sample from the same individual.
While Illumina's sequencing services business contributes a small part to the company's overall revenues — about 7.7 percent of its 2011 fourth-quarter revenues — last quarter it beat Complete Genomics in terms of total genomes shipped, with 900 genomes delivered via IGN as compared to Complete's 600.
Boyaniwsky said that the new service is not indicative of a shift in priorities for the company, which will remain focused on its instrument business, but said that human whole-genome sequencing services will be "strategically important" for the firm in the future, particularly for the clinical market. Additionally, around 75 percent of the company's whole-genome sequencing customers are already sequencing cancer samples.
"It's very smart to outsource" services for human whole-genome sequencing, she added. But, "ultimately, Illumina is an instrument company."
The recent addition of the Broad Institute to the IGN as a provider of sample-prep techniques will further enhance the cancer sequencing service, Boyaniwsky said. The Broad plans to offer a proprietary technique that enables sample prep with as little as 500 nangograms of DNA, as well as methods for sample-prep from formalin-fixed, paraffin-embedded and other challenging samples, she said (see story, this issue).
Optimized Combined Calling
The main difference between Illumina's standard human whole-genome sequencing service and its cancer-specific sequencing service is the way in which the company analyzes the data, Boyaniwsky said. The so-called "optimized combined calling method," designed to contend with heterogeneous tumor samples, also sets the company's service apart from its competitors, she said.
Analyzing tumor genomic sequence data is challenging because the tumor sample is often a mixture of both tumor and normal cells, and even the tumor cells may contain multiple subclones.
"It's not easy to discern what's tumor and what's normal," said Boyaniwsky.
Typically, calling variants involves analyzing the normal genome and the tumor genome separately and then subtracting the normal from the tumor. Illumina's approach instead "models the tumor sample as a mixture of tumor cells and normal cells and then makes the somatic calls," Boyaniwsky said. The approach "gives us more accurate results."
An in-house comparison of the two methods found that the optimized combined caller was able to detect 97 percent of a list of well-known SNPs in samples that were 40 percent tumor. At the same tumor purity level, the subtractive method detected just 77 percent of those SNPs, she said.
"It precipitously drops off because of the tumor purity," she said.
Boyaniwksy said that the company has been honing its analytical method for about a year as part of a collaboration with several undisclosed pharmaceutical companies and Cancer Research UK.
Illumina began offering the cancer sequencing service to early-access customers in the fall, and has since incorporated feedback from those customers into the analysis, she said.
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