Researchers at the Oxford Biomedical Research Center in the UK are investigating how second-generation sequencing platforms from Roche’s 454 Life Sciences and from Illumina can be used for clinical diagnostic applications, In Sequence has learned.
The scientists believe the new technologies will eventually enable clinicians to test for many genes in multiple patients in parallel, though it remains unclear whether they are already robust and user-friendly enough for routine use in a clinical setting. Initially, the researchers plan to evaluate the platforms’ ability to test for cardiovascular and retinal diseases.
At present, clinical genetic tests usually cover only one or a few genes, either because existing technologies would be too labor-intensive or expensive, according to Jenny Taylor, program director for the Genetics and Pathology theme of the OxBRC, a partnership between the Oxford Radcliffe Hospitals NHS Trust and the University of Oxford.
The center, one of a handful of such programs throughout the UK that are funded by the UK’s National Institute of Health Research to focus on translational medicine, comprises research and clinical groups at various locations in Oxford.
“There are lots of conditions where we know many causative genes but we can’t test them because it is just not feasible in a diagnostic setting,” said Taylor, who is affiliated with the Wellcome Trust Center for Human Genetics in Oxford.
Second-generation sequencing technologies could offer a solution. “What high-throughput, next-gen sequencing offers is the ability to pick up multiple genes — anything from 20 to 200 and more — and sequence those in multiple patients,” Taylor said.
However, only actual research projects will show whether the new sequencing platforms are up to the task. “The issues are going to be the technical simplicity — how complicated the experimental protocols are — and how user-friendly the software is,” according to Taylor. “The endpoint that we are looking for is running it in a routine setting, so it’s got to be robust from both those points of views, as well as meeting demands for throughput and cost-effectiveness.”
Initially, the OxBRC researchers plan to use second-generation sequencers made by Roche’s 454 Life Sciences business and Illumina to develop new sequencing-based multiple-gene tests for a number of cardiovascular and retinal diseases, according to Taylor. They also intend to explore the ability of the technologies to identify mental retardation and to perform pathogen sequencing for real-time infection surveillance.
A new sequencing facility currently being set up at the WTCHG houses two 454 Genome Sequencer FLX instruments and three Illumina Genome Analyzers that will be used in these projects, though the facility “will expand, probably, quite rapidly,” according to Taylor.
“There are lots of conditions where we know many causative genes but we can’t test them because it is just not feasible in a diagnostic setting.”
In the future, it might also acquire second-generation sequencers from other vendors, such as Applied Biosystems, but ABI’s “SOLiD really came on the market after we had made the initial commitment for the Solexa and the 454,” Taylor said.
In July, Roche Diagnostics said that it will support OxBRC researchers developing new genetic and cytogenetic tests using its 454 platform as well as microarrays — used both for sequence capture and for copy number-variation analysis — from Roche NimbleGen (see In Sequence 7/22/2008).
The collaboration with Roche developed after OxBRC scientists, in the process of acquiring the 454 platform, told the company about possible applications they were considering.
“I think their original focus was on the research applications, but they had started to consider clinical diagnostic applications, and we could assist with that,” Taylor said.
Roche is providing an undisclosed amount of funding for pilot studies, according to Taylor. Also, if experimental protocols or software need to be adapted for clinical applications, Roche “will probably work with us in order to implement those,” she said.
The reason the OxBRC invested in 454’s technology is that “we anticipate that it might be better [than other platforms] for the clinical diagnostic market,” Taylor said. “It’s partly the long reads, and partly also the sense that the multiplexing options, and the software, are potentially further ahead for diagnostic use, although the experimental protocols may be more involved.”
However, OxBRC is not wedded to the technology. As part of the WTCHG, “we have access to both [the 454 and the Illumina] platforms, so ultimately, it’s whatever is best for the clinical diagnostic purpose,” Taylor said. “Until we really get into running these experiments on a regular basis, it’s difficult to comment on that.”
For example, the long 454 reads may simplify amplicon resequencing, but the short Solexa reads may not be a problem “if we are not trying to tile the whole genome,” she said.
She and her colleagues expect preliminary results from the first studies by the end of this year or early next year.
— Bernadette Toner contributed to this article.