By Monica Heger
Microarray company Oxford Gene Technologies is moving into the next-gen sequencing space, offering targeted capture and sequencing services on Illumina's HiSeq, Life Technologies' SOLiD, and Roche's 454 GS FLX.
OGT does not currently own any sequencing machines, but is looking to purchase one by the end of the year. For the time being, it is contracting out its sequencing to academic and commercial partners while doing the capture and bioinformatics in house.
"We recognize that there's been a move toward looking at patient cohorts using next-generation sequencing," James Clough, OGT's vice president of clinical and genomic solutions, told In Sequence.
The service is an expansion of the company’s Genefficiency microarray service and is intended to appeal to customers of that service who require follow-on sequencing studies
Clough said that the company has not yet purchased a sequencer because "we want to get guidance from the market on what is the most appropriate platform" for the types of projects its customers will be doing.
Turnaround time and cost are both moving targets, said Clough, depending on the number of samples, the size of the target, the amount of sequencing, and the level of analysis a customer requires.
The company offers an "entry-level" service, which includes 2 x 100 base paired-end sequencing on the HiSeq to a minimum 30-fold average depth with analysis that includes filtering and prioritization of variants, mapping, annotation, and quality control. Price varies according to the size of the region covered, but is around £1,500 ($2,500) for custom capture, and £3,000 ($4,950) for the whole exome. Turnaround time is about six weeks, but can also vary.
Focus on the Front and Back End
OGT will have to compete with established sequencing service providers such as BGI and Illumina, both of which provide targeted sequencing in addition to whole-genome sequencing, as well as new-comer to the sequencing field Perkin Elmer, which began offering human and mouse exome sequencing services on the HiSeq 2000 earlier this year (IS 1/25/2011).
In order to distinguish itself from competitors, Clough said OGT's niche will be on the front and back end of the sequencing process.
"There's a significant gap in terms of what people are getting when they're having next-gen sequencing done," he said.
A lot of researchers are doing custom capture, but it's not always straightforward to do probe design, he noted. However, OGT already has expertise in designing probes from its microarray business, and is also a certified service provider for Agilent, whose custom in-solution Sure Select capture technology it will use for the service.
Additionally, said Clough, "a lot of our potential customers were having next-gen sequencing done and then struggling with the data."
Clough said OGT will provide as little or as much data analysis as the customer needs, up to doing functional analyses of the different mutations that are called.
Additionally, said Clough, the company has a well-established laboratory information management system that it uses to track data quality metrics for its arrays, and which it will now deploy for the sequencing business.
He said the company is focused on targeted sequencing for the moment because those are the projects its customers are pursuing due to cost constraints and the difficulty of analyzing data from whole-genome sequencing.
Even though the costs are coming down, Clough said the researchers he's talked to that have done whole-genome sequencing are struggling with the data analysis.
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Tapping the Clinical Research Market
Another reason for only offering targeted sequencing services is that Clough expects that the company's customers will be mainly clinical and translational medicine researchers.
"Whole-genome sequencing is being done, but that's primarily a focus of the major genome centers, and the majority of clinical and translational researchers are not in a genome center," he said.
OGT's early-access program for the service includes existing customers who are complementing array-based studies with next-gen sequencing, as well as new customers.
For the most part, Clough expects its customers to be in the medical genetics space, including molecular genetics and cytogenetics, from clinical research labs and the translational medicine field.
For instance, a group will "have a patient cohort that's likely to have a genetic change that's causative," and more and more, those clinical researchers are using next-gen sequencing to "find a range of unique mutations that are in the same regions" of those patients, he said.
Additionally, groups looking for genetic links to common diseases such as diabetes are increasingly using next-gen sequencing to find relevant variants.
Targeted sequencing makes particularly good sense for the clinical research market because not only is interpreting whole-genome data difficult, but sequencing patients' whole genomes raises a host of ethical questions as well.
As researchers' understanding of how to interpret whole-genome sequence data matures, the likelihood of finding variants that are clinically significant increases, and that "causes problems in terms of ethics and what to do if you find particular variants," said Clough.
Eventually, Clough said, the company would offer sequencing services in an accredited lab. Its array-CGH service already has ISO 17025 accreditation, meaning the results can be delivered to a physician for clinical interpretation. And the company is moving toward making its entire standard operating procedures fully compliant with ISO 17025.
"We're aiming to have that accreditation for our next-gen sequencing service," said Clough. With that, "we'd be able to provide sequence information back to the clinician, but they would have to make the interpretation," he added.
Making next-gen sequencing clinically applicable would require not only the accreditation, but also reducing the amount of time it takes to do the sequencing and interpretation, said Clough.
Oncology would likely be the first area where next-gen sequencing is applicable, and he noted that researchers and clinicians are already using sequencing to profile tumors and make clinical decisions.
Sequencing makes the most sense in oncology because treatment options are limited, costly, and not effective in certain subsets of patients. So, sequencing tumors is a cost-effective way to determine whether a patient should go on a certain drug regimen. As the costs of sequencing fall, it will become relevant for other diseases as well.
"It's definitely an area that is evolving very rapidly," he said.
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