Startup Silicon Valley Biosystems is hoping to build a diagnostics business by offering genomic data interpretation and sequencing services to clinicians and healthcare providers.
The company, which is backed by Sequoia Capital and has been in stealth mode for the last 18 months, said this week that is offering genomic data interpretation services using an internally developed interpretation pipeline that identifies disease-causing genetic variants and provides this to health professionals data along with relevant information from published literature about the mutations.
The company has already used its analysis pipeline to provide a diagnosis in a case of two brothers thought to have autism spectrum disorder but who actually had a rare neurodegenerative disease.
In addition to its analysis capabilities, SV Bio also offers whole-genome and exome sequencing services on the Illumina and Life Technologies platforms through three CLIA-certified laboratories located in the US, Asia, and Europe.
According to founder and CEO Dietrich Stephan, SV Bio’s goal is to provide clinicians with the tools they need to make faster, more precise, and cost-saving decisions for their patients.
Stephan, who previously co-founded direct-to-consumer genetic testing firm Navigenics, told BioInform that his new venture seeks to provide diagnostic testing for customers that is “simple, accurate, and comprehensive.”
With SV Bio, “you don’t have to be an expert user or medical geneticist or a sub-specialist to get access to the genetic testing [and results], which has been a huge bottleneck in the field up until now," he said. "We are adding that expert knowledge into the system.”
He said that the company’s algorithms are able to analyze the data and generate results that have a “sensitivity and specificity … that [is] directly in line with gold-standard assays.”
SV Bio uses a combination of expert curation and mathematical algorithms to consolidate content from both public and private sources to ensure that its customers get the “correct set of genes every time you order the test,” Stephan said.
The company is initially focusing on diseases that have a strong genetic component, including Mendelian diseases, and patients concerned about heritable cancers based on family history.
Stephan noted that the firm ultimately aims to include most genetically linked ailments with two exceptions: chronic diseases where multiple genetic factors are at play, such as age-related macular degeneration and Alzheimer’s disease; and cancer cases where testing is required in order to select a course of chemotherapy.
In the first case, Stephan explained that because risk assessment for complex genetic traits typically isn’t reimbursed by health insurance companies, physicians aren’t likely to order such tests for patients who would have to pay for them out-of-pocket.
“Diagnostics companies make their money from health insurance companies, so if tests are not reimbursed, it becomes a difficult business case,” he said.
Working with tumors, on the other hand, means tackling a very “different beast” from both a workflow and analysis perspective, he said.
With tumors, “you either have to have a presence in the operating room or need to deal with formalin-fixed tissues as an input material and then you’re looking at different depths of sequencing coverage,” he said. In addition, such a service would require sequencing both the cancer and germline genomes as well as dealing with “mapping that information against drugs,” he said.
This strategy sets the firm apart from some other genomic interpretation firms in the market, such as Foundation Medicine, which have targeted oncology for their services. A number of other informatics-oriented firms, such as MolecularHealth, MediSapiens, Five3 Genomics, and Knome have also identified oncology as an initial market for their clinical genome analysis offerings.
Stephan said SV Bio would eventually like to take on tumor analysis as it pertains to treatment, but “we are not starting there.”
According to the company, its analysis platform uses a set of proprietary algorithms to analyze data from next-generation sequencers and to determine with “clinical-grade sensitivity and specificity” which genetic variants within the patient’s DNA sequence are influencing a disease or condition.
For example, it can identify large insertions and deletions in NGS data that are, in some cases, a major cause of human disease; an area where some gene panel-based tests fall short, Stephan told BioInform.
The pipeline then trims long lists of variants to find the most relevant ones by analyzing known polymorphisms and mutations in the context of public resources such as the 1000 Genomes project dataset, the Single Nucleotide Polymorphism database, as well as some undisclosed proprietary resources. It then applies an internally developed classification engine, which “assigns causality” to new variants based on more over 100 attributes, he said.
The system then outputs a three-page report that includes the causative variants; available evidence from published literature linking the mutation to a particular disease; and the quality control metrics used by the pipeline so that more experienced users can check to see whether the pipeline was run properly, he said.
Furthermore, the system keeps track of variants identified in previous patients and applies this information to its analysis of new patient data, he said.
SV Bio, also has a cadre of experts on hand to help clinicians interpret what the results mean for their patients, he said.
The company claims that it is able to provide clinical interpretation of genomic data at the point of care. According to Stephan, that’s true in cases where the patient’s genome or exome has already been sequenced.
Where the data is available, it “literally takes minutes” for SV Bio’s pipeline to complete the analysis and generate reports, he said.
Those who don’t have their genomes sequenced will have to wait longer — “a matter of weeks” — to get their results back, he said.
However, with sequencing costs continuing to drop, Stephan expects that increasingly larger swathes of the population will choose to get their DNA sequenced and that this information will be included in their electronic medical records where it can be incorporated into the diagnostic process.
SV Bio charges for its service on a per-test basis — with a price tag that ranges from the low to mid thousands — and offers variable pricing depending on “the amount of content the physician is interested in looking at,” as well as the complexity of the analysis required. Stephan added that the firm's fees are “within the range of current diagnostic testing services."
SV Bio said that its diagnostic testing services are being used by clinicians in hospitals and centers of excellence.
The platform has already been used in at least one case, the company said, involving a family with two boys who were thought to have an autism spectrum disorder.
In an email, Michael Chez, director of pediatric neurology at the Sutter Neuroscience Institute, explained that the older of the two siblings was experiencing loss of coordination seizures, as well as problems walking and eating. The younger child had worsening speech delays and also had seizures.
“Prior to seeing me [both children] had extensive genetic and imaging EEG and blood testing at UCSF Mayo Stanford and Sutter Sacramento,” he told BioInform. Since these tests didn’t show any defects, Chez said he decided to try whole-genome sequencing.
SV Bio analyzed genomic data from the patients and eventually identified genetic mutation in the tripeptidyl-peptidase 1, or TPP1, gene that causes a rare neurodegenerative disease called late-infantile neuronal ceroid lipofuscinosis as the culprit in both cases.
It did take a few months to get the results of the analysis back, according to Chez, but he said that was likely due in part to the fact that the procedure was still being tested at that time. The response time would “probably have been quicker otherwise,” he said.
However, SV Bio’s findings were “extremely” helpful for the patients, he said.
For one thing, it meant that the children could gain access to experimental treatments that would otherwise have been delayed.
“The boys are on a [treatment] protocol that we started and ... they are candidates now for other future drug trials as they become available,” he said.