Oxford Gene Technology has introduced a new array that it claims can be used in combination with clinical exome sequencing to improve diagnostic yield.
The CytoSure Medical Exome Array is an exon-focused chip capable of detecting medically relevant microdeletions and duplications in approximately 4,600 genes. Oxford, UK-based OGT designed the array with collaborators at Emory Genetics Laboratory in Atlanta. OGT and EGL have in recent years developed a menu of CytoSure Molecular Arrays that target genes associated with two dozen diseases and disorders.
According to James Clough, executive vice president of commercial operations at OGT, the company's latest array was borne out of the MedicalExome Project, an effort involving researchers at EGL and other institutions to offer coverage of all medically relevant genes, about 4,600, from the 22,000 genes covered by exome sequencing.
Clough spoke with BioArray News about the development of the new array at the American College of Medical Genetics and Genomics meeting, held last week in Nashville, Tenn.
"In recognition that the clinical testing market is moving to exomes, although all of these products are research use only, there is a realization that if you do not do copy number, you are missing part of the jigsaw puzzle," said Clough.
While exome sequencing excels at delivering point mutations, the approach is "nowhere where it needs to be" when it comes to copy number data, said Clough, with a "great amount of false positives." At the same time, he maintained that it is "well known that arrays are very good at copy number detection." Therefore, EGL requested that OGT create the CytoSure Medical Exome Array to deliver CNV data that could be used together with exome sequencing data to deliver more comprehensive results.
"If you only do the exome, you miss significant diagnostic yield," said Clough.
In November BioArray News interviewed Madhuri Hegde, EGL's executive director, about the MedicalExome project, as well as her lab's relationship with OGT. At the time, she hinted that the creation of such an array might be necessary.
"It is possible that we will have to use complementary methods to detect those changes not currently detected by NGS," Hegde said at the time.
In addition to exon-focused coverage of 4,600 genes, OGT's CytoSure Medical Exome Array includes a backbone of probes similar to what is in its constitutional comparative genomic hybridization arrays, making it a "tool to capture as many of the copy number variants as you can." The array is manufactured by Agilent Technologies in its million-feature format.
Custom versions of the array are also available, including slides containing two 400,000-spot arrays; slides containing four 180,000-spot arrays; and slides containing eight 60,000-spot arrays. Clients can work with OGT to design thir own chips, which can be used with its CytoSure Interpret data analysis software.
"We've got 4,600 genes with all of the probes you can get within those genes that would perform well," said Clough. "It's a bit like a pick-and-mix sweet shop," he said. "That's all the sweets we've got."
In terms of the chips' place in genetic labs' workflows, Clough speculated that the array would be used as a reflex test, meaning that if exome sequencing does not produce significant findings, labs could use the Medical Exome Array to look at CNVs. And due the fact that the chip appeals to clinical genetic laboratories that run exome sequencing, Clough speculated that the greatest demand for the new tool would come from the US.
"If you look at the genetics testing market, North America leads," said Clough. "I don't know what the number of exomes being run clinically in the UK is, but it is a trivial number compared to the number run by large centers in the US," he said. "I have had people tell me they are going to do 10,000 exomes this year," Clough added. "There aren't 10,000 exomes being done in the whole of Europe."
OGT is better poised to capture some of that market having opened a US office outside New York City in 2012, said Clough.
"The interest is coming from the centers that are doing exome sequencing," he said. "They recognize the need."