CHICAGO (GenomeWeb) – As it gets its precision medicine program off the ground, Sanford Imagenetics, the molecular diagnostic laboratory of Sanford Health, is using a new product from Genoox to refine its test panels as well as improve interpretation of genomic sequences.
In July, Tel Aviv, Israel-based Genoox soft-launched Franklin, a classification tool that correlates medical evidence with an artificial intelligence engine to help geneticists and genetic counselors adhere to American College of Medical Genetics and Genomics guidelines.
"What we have developed here as a free tool for the community is the ability to classify variants using artificial intelligence … and still comply with the medical guidelines," said Genoox Cofounder and CEO Amir Trabelsi.
The new product, named after early DNA researcher Rosalind Franklin, addresses the challenge of keeping up with rapidly changing medical evidence when interpreting variant reports. In the process, it helps clinicians eliminate confusion around variants of unknown significance.
Franklin mines free text in scientific literature, looking for keywords that might correlate to variants found in sequencing reports.
"We see this as a free tool for the community to help with interpretation, to stay up to date with all the data that is out there," Trabelsi said. "You can classify a patient with a VUS variant, but one or two weeks after, the science [may have] changed and the literature has changed. You can get updates on that as well."
Trabelsi mentioned a case in which the diagnosis for a four-year-old child was delayed because the laboratory initially found variants of unknown significance. "We were able to alert the clinician that some of the evidence had changed. Based on that, they were able to provide the improved diagnosis," he said.
"We're not a replacement for the clinician. We're not taking the decision [away from them]," Trabelsi added. "We just help to clarify the evidence that exists and provide our prediction based on the clinical guidelines."
Michelle Moore, senior lab genetic counselor at Sioux Falls, South Dakota-based Sanford Imagenetics, learned about Genoox and Franklin at the ACMG annual meeting held earlier this year in Charlotte, North Carolina. At the time, Sanford Imagenetics was getting ready to release a laboratory-developed genotype screening array following the ACMG-59 gene list.
"We had to decide on variants from our platform to include on the screening platform," Moore said. Sanford quickly became an early adopter of Franklin as a way of determining which variants should be considered pathogenic and thus included on the array.
"I've been using Franklin to confirm that I'm getting the right spots, seeing what points from the ACMG guidelines that they think that those variants hit or don't hit, and using it to compare to other sources to see if I'm on the right track," Moore said.
"You don't want to be detecting something that means nothing, but also you don't want to be disclaiming and not detecting a variant that was a VUS, but now has significant evidence that it actually means something," she explained.
Sanford Imagenetics took advantage of the occasion and the new informatics technology to review all of its VUS.
The lab-developed test launched in March, branded as Sanford Chip. Primary care physicians there can order the screening, which involves analyzing a small blood sample to determine a patient's risk for various diseases as well as to create a pharmacogenomic profile, according to the health system.
Sanford right now is using Franklin only for its screening panel. "We are hoping that our lab will move forward to whole-exome and whole-genome sequencing at some point, and then it would be diagnostic testing," Moore said. "That's where a lot of the variant interpretation is for a lot of the bigger laboratories that could benefit from Franklin, but that's not how were using it currently."
Noting that the cost of whole-exome and whole-genome sequencing continues to fall rapidly, such tests are becoming more common. "It is actually under discussion that [WES and WGS] might become a first-tier test instead of the last-resort test as it is right now, so variant interpretation is the entire part of that test," Moore said.
Agreeing that WGS represents the next wave of genetic diagnostics, Trabelsi said that Genoox is marketing Franklin to large academic institutions and genomic labs for this purpose. "We see many panels for specific conditions, like epilepsy or developmental delays," he said.
"As we're seeing more and more applications going through first-tier exome and [next-generation sequencing], just the amount of work that's needed in order to evaluate and to interpret these variants grows," he said. "With whole-genome, you have more than 10 million variants that exist. There's just a growing demand for tools to help you with that. We see the need from the community for such offerings."