A year and a half after offering its first inherited disease panel on Life Technologies' SOLiD platform, Spanish molecular diagnostics and research services company Sistemas Genómicos has increased the size of that panel and has added new panels for a number of indications. The company has also adopted the Roche 454 GS Junior platform for BRCA testing and recently brought in the Illumina MiSeq for evaluation.
Sistemas started offering a diagnostic cardiology gene panel on the SOLiD 4 in early 2011. That panel comprises a number of sub-panels that range in size from three to 72 genes (IS 2/1/2011).
Since then, the Valencia-based firm has expanded the total number of genes in its cardiology panel to 90 and plans another upgrade, to nearly 200 genes, in the near future, according to David Garcia, the company's business development manager.
Sistemas has also added a 22-gene oncology panel with subpanels for a number of hereditary cancers, including breast, ovarian, and colorectal cancer. While most of these subpanels also run on the SOLiD platform, the firm provides testing for the BRCA1 and BRCA2 genes alone on the 454 GS Junior, which Garcia said is more efficient than using the SOLiD and has a faster turnaround time — 15 days instead of 90 days. The company is also working on additional tests to run on the 454, for example for colorectal cancer, that are currently being validated.
In June, the company added a hearing loss panel on SOLiD that covers 67 genes associated with syndromic and non-syndromic hearing impairment. While conventional sequencing has a success rate of about 40 percent for diagnosing hearing loss, Sistemas expects its test, called the OTOGeneProfile, will bring this rate up to 70 percent.
And earlier this month, Sistemas launched a neurology disease panel, called NEURO GeneProfile that includes 285 genes related to a variety of neurological diseases, including Charcot-Marie-Tooth disease; hereditary ataxias; hereditary spastic paraplegias; myasthenia and myasthenic syndromes; young onset Parkinson's disease; and myopathies, muscular dystrophies, and spinal cord atrophies.
The company intends to launch additional gene panels in other disease areas in the future but has no immediate plans to do so. "Our idea is to include all diseases for which it would make sense from an economic standpoint to sequence many genes at the same time," Garcia said. In the long term, he added, the firm might also broaden its scope from inherited disease testing to tumor analysis.
Exome sequencing is not offered by Sistemas for diagnostics but only for research purposes. "We're still not completely sure what the clinical indication would be," Garcia explained.
Along with expanding its testing menu, Sistemas has increased its sequencing capacity by adding a SOLiD 5500xl to its SOLiD 4, complemented by its 454 GS Junior.
In addition, the firm just brought in the Illumina MiSeq for in-house testing. While this platform could potentially reduce the turnaround time of tests, Garcia stressed that the company has no hands-on experience with it yet. "Probably in three to four months, we will have a clearer idea about what we will be doing with the MiSeq. But of course our intent is to use this technology for diagnosis," Garcia said. "If it works well, we may run some panels on the MiSeq, or some other diagnostics."
For the time being, large gene panels will remain on the SOLiD, and the company intends to keep that platform as long as it is supported well by Life Technologies. "If they provide a good service and keep improving, we'll probably stick to the SOLiD until we have something that is better in some aspects," Garcia said. "There is still no technology that we can say, 'it's the best,' … they all have their strengths and their weaknesses." He added that the firm has not been testing Life Tech's PGM or Ion Proton platforms.
Sistemas uses a variety of tools to analyze and interpret variants. These include Align GVGD, SIFT, and PolyPhen-2, which help to prioritize variants of unknown significance according to their pathogenicity; conservation scores to assess whether a variant is in a functional domain of a protein; and several public and private databases, including disease-specific ones.
The company provides doctors with a report, prepared by a group of geneticists with expertise in different medical areas, that contains clinical information associated with any mutations detected and is intended to help doctors make a diagnosis. The report also includes recommendations for clinical management of patients. In addition, Sistemas allows doctors to consult with its team of geneticists directly on the interpretation of the results.
"This customized approach is necessary as doctors are increasingly aware of genetics and want to understand and control the different parameters of the analytic process," Garcia said. For example, some doctors ask that the PSEN1 and PSEN2 genes, which are part of Sistemas' cardiology panel, be excluded from the report because they are also associated with Alzheimer's disease. "It is up to the doctors to instruct us if it is appropriate to report the incidental findings on these genes on a case by case basis," he said.
According to Garcia, the bottleneck for providing testing "is now interpretation of the data, not generation of the data." Sequencing has become less and less expensive, "but it cannot become much cheaper," he said.
The company has already expanded its team of bioinformaticians, and will likely continue to do so. "This is one of the ways our company will have to grow in the future if we want to provide a good service," he said.
Overall, the company has provided several hundred next-gen sequencing diagnostic tests so far. Most patient samples come from Europe, South America, and Canada, though Sistemas offers testing worldwide and has analyzed samples from other countries as well.
Its US customers have been using the panels only in research studies, but the company hopes to expand its diagnostic services to the US market once it receives CLIA certification for its laboratory, which is currently pending.
Through economies of scale, the 5500xl upgrade, and streamlined bioinformatics, the firm has been able to cut its prices, from €3,500 ($4,500) for its most expensive cardiology panel in 2011 to less than €2,000 ($2,500) for its most expensive panel today. Turnaround time for the SOLiD panels is still 90 days, and any clinically interesting variants are still confirmed by Sanger sequencing.