Tute Genomics has partnered with UniConnect to support next-generation sequencing-based newborn screening panels developed by Newborn Screening Ontario (NSO), a molecular testing laboratory at the Children's Hospital of Eastern Ontario.
The arrangement marks the first time Tute is putting the Knome technology to work after acquiring the company's assets in November for an undisclosed amount. Specifically, Tute is providing NSO with cloud-based pipelines for sequence alignment, variant calling, annotation, interpretation, and results reporting. Meantime, UniConnect is providing a local laboratory information management system that will be used for managing and tracking samples, tools, and projects. NSO will have tools to assess the quality of its data and projects, store multiple file types, and manage different datasets.
NSO's newborn screening program tests patients in Ontario for rare but treatable diseases. Since the lab opened in 2006, it has provided testing to more than 1 million newborns in the region, and diagnosed More than 1,250 newborns with rare diseases.
Tute and UniConnect's software will support two NGS-based panels for confirming the presence of rare but treatable conditions that have been diagnosed by biochemical testing. The first of these covers 412 nuclear encoded genes that are associated with various forms of mitochondrial disease. A second panel covers 51 genes that are responsible for 22 primary and 16 secondary inborn errors of metabolism and congenital adrenal hyperplasia, as well as 20 genes responsible for 80 percent to 90 percent of severe combined immunodeficiency cases. In the future NSO could develop a third panel to sequence the cystic fibrosis transmembrane conductance regulator protein directly from blood spots.
As part of a validation process, the NSO will initially test the panel on samples from newborns that tested positive using existing screening methods. They'll eventually expand it to screen all of the newborns that have screened positive in the province. Ultimately, the lab hopes that the panels will replace or be used in tandem with traditional biochemical screening to test the roughly 145,000 babies that are born in Ontario annually, according to Josh Forsythe, Tute's vice president of marketing.
The Ontario Ministry of Health and Long Term Care contracted the NSO to develop and offer the gene panels. The move is the latest in a series of provincial repatriation efforts aimed at increasing genetic testing capacity and lowering costs associated with outsourcing tests to facilities outside Canada.
"[It] expand[s] our ability to deliver high-quality results and will expand access to the latest genetic testing technology for children and adults within the province of Ontario," Dennis Bulman, senior molecular scientist at NSO, said in a statement. "Our ability to offer 'in-province' testing allows for more timely diagnosis and treatment for these rare diseases."
That decision to keep testing in house is a significant one given that many hospital labs typically outsource testing to third parties, according to Tute's Forsythe. For example, Ontario outsources some 85 percent of its genetic tests to partners in the US. "There's now pressure and incentives for these groups to bring clinical sequencing in house," he told GenomeWeb. "Bioinformatics is the critical piece to do that and that's what people are missing."
This partnership marks Tute's first full implementation of the interpretation software it acquired from Knome. Tute has tested the now cloud-based Knome tech as part of early-access pilots with unnamed users but this is the first time it will be fully implemented as part of a clinical workflow, Forsythe said.
It's also the first publicly announced pediatric project that the company is engaging in. Privately, Tute has worked with several Provo, Utah-based pediatric hospitals and patient advocacy groups such as Aware of Angels, which raises awareness for children with rare diseases, to provide sequencing for the littlest patients.
"The earlier a child is diagnosed, the better it is," he said. "If we can start sequencing newborns ... at birth [then] whether there is a problem that manifests at birth or at three years old, the data is there. As soon as there is a problem, that data can be interrogated to find the answer that child needs." Tute has also worked with UniConnect on a number of other unnamed projects in the Utah area — a partnership born out of the firms' proximity to each other, Forsythe said.
NSO provided the companies with a comprehensive list of requirements for its software infrastructure. The system that Tute put together combines variant interpretation capabilities from the legacy Knome system, which offers functionality for developing in silico panels and supporting sequencing assays, as well as some of Tute's own capabilities including Tute Drive, a tool that lets users automatically upload data from local servers to the cloud as well as launch data analysis pipelines as needed. Users can also check the quality of their sequences prior to uploading them to the cloud for interpretation and generate customized quality control reports for fastq, bam, or vcf files.
The analysis pipelines available in the system have also been customized to match the specific library prep kits, filtering routines, and other requirements of the NSO gene panels. These particular gene panels are designed to identify single nucleotide variants as well as small insertions and deletions that are associated with the genetic diseases that they are designed to test for. Forsythe declined to disclose specific details about the pipelines that Tute is providing for the NSO.
Managing a molecular lab
For its part, UniConnect is providing a customized version of Precision Molecular Diagnostics, an iteration of UniFlow, its laboratory process management system designed specifically for molecular diagnostics laboratories. UniConnect launched PrecisionMDx in 2014 with Exosome Diagnostics and Selah Genomics signing on as early-access customers. The system leverages the underlying UniFlow technology which offers a proprietary database scheme for representing relationships between objects in a way that provides complete traceability at all points in a process. It uses a tag-based language that automatically creates and maintains relationships in the database. The system supports molecular diagnostics lab workflows from sample entry through to final report. It includes tools to create customized workflows for assays, as well as modifiable reports that combine lab analysis with information from the literature and present results in an understandable fashion.
PMDx is a cut above existing LIMS and laboratory information systems (LIS) because it includes tailored capabilities for the needs of molecular labs like NSO. Standard LIS and LIMS support activities in many biomedical domains, "but when it comes to the realm of molecular analysis there are many, many lab steps involving a variety of different kinds of instrumentation, and in NGS this analysis can take place over days," said Richard Mandahl, UniConnect's vice president of business development. "That kind of capability is not what high-throughput, high-transaction, more shallow process elements of LIS systems were designed to do. Moreover, he added, "force-fitting that into a molecular realm is not working very well."
UniConnect's system, in contrast, was designed from the ground up to support omics-based labs and companies, Mandahl told GenomeWeb. The system has been used by customers such as Vivia Biotech, who selected UniFlow to manage patient samples and drug compounds. Like it is now doing with NSO, UniConnect has also deployed PMDx at the Children's Hospital Colorado's molecular diagnostics laboratory through a deal signed last year.
"We've continued to evolve and drive our capabilities to on the one hand meet the broad requirements of the molecular lab and at the same time be adaptable enough to go in and configure systems to be very tightly matched to the exact work that’s going on in a specific lab," Mandahl said.
UniConnect also offers both of its tools on the Google cloud, giving customers the option of using the software remotely or implementing either tool locally. The NSO is using a local installation of PMDx and so will keep all of protected health information in house. NSO is implementing the full PMDx system including a next-generation sequencing module that includes tailored implementations for Illumina MiSeq and Thermo Scientific Ion Torrent platforms as well as capabilities for tracking and controlling NGS analytic processes.
UniConnect is currently implementing PMDx at the NSO lab, customizing it to researchers needs and training authorized members of the NSO team so that they can make changes to the system as needed in future, he said.