NEW YORK (GenomeWeb) – Earlier this week, the Garvan Institute of Medical Research unveiled a commercial clinical whole-genome sequencing service targeting rare and inherited diseases and disorders.
The test will be offered by Genome.One, a new company owned by and based at the Garvan Institute, which also said this week that it will use DNAnexus' platform to run the computational pipeline that it will use to analyze data from the new service.
It is a continuation of a partnership that began last year when Garvan tapped DNAnexus' platform to process, manage, analyze, and share sequence from its existing genomics-based research initiatives as well as to provide computational support for a planned commercial genome sequencing service.
"When we started working with [Garvan] a few years ago, they were involved in a number of research projects [but] one of their aspirations was to turn that expertise to use in the clinical setting," Andrew Lim, DNAnexus' vice president for Asia-Pacific, noted in a conversation with GenomeWeb this week. "They've gone through a process with DNAnexus to enable our platform to act as … their backbone for doing the bioinformatics and the analytics for their clinical testing activities."
In 2013, DNAnexus began offering cloud infrastructure specifically for use by clinical testing laboratories seeking a system to run their analysis pipelines and store data. The Amazon Web Services-based platform includes auditing capabilities, data and pipeline versioning, encryptions, and firewalls, and is equipped with application programming interfaces that labs can use to move testing algorithms and pipelines to the cloud and build customized workflows.
Since the launch, the company's platform has supported clinically-orientated initiatives in the US and abroad such as the Intensive Trial of Omics in Cancer (ITOMIC), which seeks to find more effective cancer therapies by analyzing multiple sources of information and tapping into a network of domain experts. A recent paper published in the Journal of the National Comprehensive Cancer Network this year describes the results of analyzing data from a single triple-negative breast cancer patient enrolled in the trial. Last year, Natera selected the company's platform to support data analysis, storage, and sharing for its non-invasive prenatal screening testing. DNAnexus also supports Baylor College of Medicine's Cohorts for Heart and Aging Research in Genomic Epidemiology project, which explores genes' contributions to heart disease and aging.
Over the last year, Garvan has used DNAnexus' platform to manage, analyze, and secure the massive quantities of genomic data generated by its Illumina HiSeq X Ten system — Garvan was one of the first three customers for the X Ten when the system was first launched in 2014. Marcel Dinger, head of the Garvan's Kinghorn Centre for Clinical Genomics, told GenomeWeb that in the years since the purchase, the institute has used X Ten to offer fee-for-service sequencing services for research purposes but it always intended to put the system to work for clinicians and their patients.
To that end, Garvan researchers spent the last 18 months getting both their sequencing system and computational pipeline certified for clinical use by the Australian National Association of Testing Authorities including drafting appropriate documentation for the pipeline, running repeated testing, and performing multiple quality checks.
"To operate the X Ten and make an impact in the clinical diagnostics space you need a lot of precision and automation," George Asimenos, DNAnexus' vice president, noted in a conversation with GenomeWeb. And the DNAnexus platform is well-suited for these tasks. "It can provide that level of automation, compliance, reproducibility, security, and peace of mind for everything that Garvan needs to do."
The Garvan pipeline, which runs on the DNAnexus platform, was named one of the winners in the precisionFDA Truth Challenge which took place earlier this year — it won the award for highest SNP precision of the submitted entries. The pipeline basically emulates the Broad Institute's Genome Analysis Toolkit BWA best practice workflow but it has been fine-tuned and optimized for more precise variant calling, Dinger said. Following sequencing, FastQ files are uploaded to the DNAnexus platform for the alignment and variant calling steps. They then take the data off the platform for the variant filtering and interpretation steps.
"All their protocols [are] HIPAA compliant which was very attractive for clinical use," Dinger said explaining Garvan's rationale for opting to use DNAnexus' platform for Genome.One. He also highlighted the company's expertise with cloud infrastructure and the fact that its cloud-based platform provides ample space to scale and expand sequencing services as needed. "For us, going to cloud was very attractive [because] it meant we didn't have to build out our own computing center here any further" which would have been costlier. Also, DNAnexus has implemented the necessary security measures, providing wrappers for pipelines among other features to enable its customers to best utilize cloud infrastructure, he added. They have done "a lot of the heavy lifting so that was attractive."
Genome.One's service will be an end-to-end test from blood samples or purified(?) DNA through to a fully interpreted pathology report with an initial turnaround time of 8-12 weeks, but Dinger believes they'll be able to eventually get those numbers down. Physicians can get either a paper or pdf version of the report. Clinicians do not receive any of the underlying sequence or variant call files; however, Garvan hopes to implement a mechanism where data from consented patients could potentially be made accessible to researchers for further study particularly in cases where no particular diagnosis is made.
The test is initially available for a reduced price of $4,360 per individual proband and $2,600 for each additional family member. Pricing for testing larger numbers of patients is open for negotiating. The company is focusing initially on rare genetic diseases because they believe that's where the greatest need is in the market and where whole-genome sequencing adds the most value, Dinger said. However, they do expect to expand the service into other areas in future. This includes testing for cardiovascular and renal diseases and assessing cancer predisposition, among other areas.
Garvan expects that the Genome.One service could triple the diagnosis rates for Australians living with rare and genetic conditions from around 20 percent to around 40 to 60 percent. An estimated two percent of Australians are affected with a rare disorder so capacity-wise, Dinger expects that Genome.One could sequence as many as 100 to 200 individuals a month initially. "The sequencing piece is actually the easy part," he said. "I think our clinical capacity" — how quickly clinical geneticists can review and sign out reports — "will be the rate-limiting step as we scale up."