GenomeQuest this week said that the Emory Genetics Laboratory is using its GQ-Dx software to support a suite of sequencing-based diagnostic tests it offers through its CLIA-certified facility.
The lab is currently validating the software for use with gene panel tests for autism, X-linked intellectual disability, muscular dystrophy, and congenital disorders of glycosylation. It also plans to use the software to support upcoming gene panel tests for oncology, hearing loss, and cardiomyopathy, as well as a clinical exome sequencing service that it will launch in the first half of the year.
GenomeQuest CEO Richard Resnick told BioInform at Cambridge Healthtech Institute's Molecular Medicine Tri-Conference this week that Emory is the eighth lab to implement its software for clinical sequencing. Last summer, the University of Iowa's Molecular Otolaryngology and Renal Research Laboratory agreed to use GQ-Dx software for an NGS-based test for genetic hearing loss. More recently, the company awarded six labs $120,000 worth of software and services under its GenomeQuest Lab Grant Program, intended to help labs migrate multiple Sanger-based gene tests into a single, comprehensive NGS-based test (BI 1/13/12).
Resnick said that the clinical market still represents only about 20 percent of the privately held company's revenues, with the remainder coming from its IP sequence database business. He noted, however, that the breakdown in effort within the company between the two businesses is closer to 50/50 since it considers the clinical market to be a higher growth opportunity.
He said that in addition to seeking more agreements like the Emory deal, GenomeQuest is also looking to expand its presence in the clinical market through partnerships with large diagnostic firms. However, he declined to provide further details on that strategy.
The Emory agreement is a significant win for the company since the lab was among the first to adopt NGS-based testing, launching its first gene panels in 2010. Madhuri Hegde, associate professor at the Emory University School of Medicine Department of Human Genetics and the scientific director of the Emory Genetics Laboratory, is a member of GenomeQuest's clinical advisory board, but Resnick said that the fact that the lab is now a "paying customer" for the company's software validates its utility in the clinical setting.
Hegde told BioInform via e-mail that the lab has to date been using Softgenetics' NextGene software as the primary analysis tool for its NGS-based gene panels. "GQ-Dx will not replace NextGene," she said. Rather, "it will be used in parallel" for all samples.
She noted that the lab uses two software packages for analyzing Sanger sequencing data — Life Technologies' SeqScape and Softgenetics' Mutation Surveyor — which use different algorithms and therefore provide additional confidence when used in parallel. "It is known that bioinformatics tools in the NGS space are rapidly evolving and we hope to derive the same benefit from using two completely different programs in our laboratory," she said.
Hegde said that GQ-Dx's cloud-based model was a key feature in deciding to adopt the software since it reduces the lab's in-house data storage requirements, which can be a "significant investment." In particular, once the group begins offering clinical exome sequencing later in the year, "the storage needs are going to grow," she said.
In addition, Hegde said that GQ-Dx's reporting "can be formatted to clinical laboratory needs and will make it easier to manage data."
This ability is "impressive," she said, and could reduce the group's analysis time by as much as 50 percent.
Hegde noted that the software provides a number of helpful features out of the box, including the ability to link variants directly to existing databases such as dbSNP, HGMD, and locus-specific databases, and the ability to assess pathogenicity of variants via SIFT. It also allows the lab to integrate this information with its internal database and reporting software so it can ensure that any variants it reclassifies are included in final reports.
"Most importantly, the entire report format can be customized to laboratory needs," she said, allowing the group to run side-by-side comparisons with NextGene results.
There are currently no standard guidelines from CLIA or the College of American Pathologists regarding the best way to validate NGS analysis software in the clinical setting, so Emory has conducted internal validation for its diagnostic sequencing pipeline. Hegde said the lab will take the same validation steps for GQ-Dx as it did with NextGene "for all existing and new targeted panels and exomes."
The lab has had the software for about a month and has carried out an "extensive evaluation" by running samples that were previously used for validating NextGene, Hegde said.
For example, she noted that one of the group's validation samples, which it described in a recently published study on congenital disorders of glycosylation, has a point mutation on one allele and a 22-base deletion on the other. "It is known that it is not particularly easy to detect indels from exome [sequencing data,]" she said. Using this sample and others, "we have done such extensive evaluation of both NextGene and GQ-DX, compared them with other programs, and have established a relationship to improve the programs."
GenomeQuest this week also launched a new version of GQ-Dx with expanded content and new capabilities intended to improve clinical decision support.
The software now draws from an expanded base of variant associations from sources including GeneReviews, GeneTests, dbSNP, OMIM, COSMIC, SIFT, and Polyphen. The company has also licensed HGMD from Biobase so that it can offer that data under a sublicense.
Resnick noted that the company has improved the "knowledge engine" that integrates data across these resources with an eye toward the needs of clinical labs. For example, each variant includes information about whether it is pathogenetic or not as well as which drugs are associated with it. The software also has new capabilities to detect large insertions and deletions, he said.
He said that the company also improved the software's interface to make it easier for clinical geneticists and other users to interact with the data. The upgrade makes it easier for users to ask questions and also provides simpler results, he said. Rather than providing a list of all potential variants in a sample, for example, it provides users with a report about "the three variants that are known to be pathogenic, and the 30 that might be," he said.
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