Clinical sequencing startup Parabase Genomics announced this month that it is developing a targeted sequencing test for neonates suspected to be suffering from genetic diseases.
Parabase's CEO Andy Bhattacharjee discussed the company's plans for what it calls the Lifetime test at the Consumer Genetics Conference earlier this month.
Bhattacharjee told Clinical Sequencing News that the company plans to offer the test first for patients in the neonatal intensive care unit, where it believes rapid-turnaround targeted sequencing can improve the diagnosis and treatment of sick infants right now. Eventually, though, as sequencing costs go down, Parabase hopes to move the test into the routine newborn screening space.
In the future, Bhattacharjee said, exome or whole-genome sequencing will likely replace the group's targeted approach. But, he said the company believes targeted sequencing is necessary for a feasible clinical test right now.
"You want a targeted panel for the most part, to tease apart the diseases that need to be tackled in the NICU … because with those we can put them on the right treatment path and actually rescue those babies," Bhattacharjee said.
"Whole-genome sequencing will be very useful when it gets there, but not that many people will be able to pay $13,000 in the NICU out of pocket to use this test." A $1,000 test, however, "as long as it is practical and can be processed quickly, would give much faster commercial traction."
A group from Children's Mercy Hospital led by Stephen Kingsmore is also doing clinical sequencing in the NICU, but is going with a whole-genome approach. Kingsmore's team recently published a proof-of-principle study in Science Translational Medicine describing the first cases that have gone through the process, which they call STAT-seq (CSN 10/3/2012).
Parabase intends to launch its targeted Lifetime test by the second half of 2013. The test will cover about 1,000 genetic disorders that affect neonates — many more than current single-gene tests, but less than would be possible with whole-genome sequencing.
According to Bhattacharjee, if initial testing using the targeted Lifetime assay fails to offer a diagnosis, Parabase will offer an option to reflex to exome or whole-genome sequencing. "And a few years down the road, we will offer one single test, and offer the choice to the doctor whether he wants to use an in silico panel or the [whole genome.]"
The company has been developing Lifetime using the Illumina HiSeq 2000 with the goal to move to the HiSeq 2500 or the MiSeq when the test is commercialized. However, Dana Alexandrunas, Parabase's director of sales and marketing, told CSN that the company's ultimate goal is to be platform agnostic.
According to Bhattacharjee, the team has a good idea of everything that will be targeted by the test. We have done some pilot testing … [And] by next year, we should have some good early product that we can deploy," he said.
He said the company's goal is to reduce the sequencing turnaround time to less than three days with no more than a week from when a patient is sampled to when they receive a result.
As Parabase works toward releasing Lifetime next year, Alexandrunas said the company has launched a three-tiered exome sequencing service.
"At a higher level we believe we need to offer the full complement of technologies available, so we will offer whole-genome and whole-exome and targeted sequencing," she explained.
"There are kids who are already sick who need help, who have been poked and prodded for years and still have no answers – so that's where the exome [sequencing] fits in. We can help them now, while we work on the targeted NICU test," she said.
According to Alexandrunas, Parabase is offering three tiers of what the company calls the Lifetime Exome. The first is a clinical exome for $7,500, run in a CLIA-certified lab, which will be presented to customers as a medically actionable report and can be submitted for reimbursement, she said. The second is a "clinical research exome," priced at $4,500, for researchers who don't need the information to drive patient care. This service will include genome analysis from bioinformatics firm Omicia. The third tier, with a $1,200 list price, is a straight research exome.
For the targeted Lifetime NICU test, Parabase is currently working through several research projects with partner groups focused on subsets of neonatal diseases to validate the targeted panel's ability to diagnose the disorders it will target.
"Unlike other [sequencing tests,] our panel is going to be really functionally validated," Alexandrunas said.
"With some of the grants and collaborations we have going on we have access to real live patient cases – so we are not just conceiving of this and saying theoretically this is a gene – we are taking samples from these babies and testing it out to make sure [we can identify known and new mutations, and correctly associate them with disease.]"
Bhattacharjee said that the company hopes to validate Lifetime beyond purely functional standards like CAP and CLIA.
"Testing labs have done exome sequencing tests, and everyone sells them. But no one tests to see if they are accurate. Typically SNP calls serve as proxy … but those are not really good assumptions to make. You really want to see how many times you catch cystic fibrosis, PKU, et cetera," he said.
"So that's the painful exercise we are going through with our collaborations, putting together grants, research projects to test the same story 1,000 times in each of these diseases to collect data and be sure the test will be robust."
The company's first projects have been with genes and diseases that are critical in the neonatal phase, and for which there is some opportunity for treatment, he said.
At the conference, Bhattacharjee said Parabase has submitted an application for a $200,000 SBIR grant to study hearing loss disorders that is currently in the final stages of review.
Other projects, like one working with Amish Mennonite patients, are being addressed with private funding.
"We get a lot more diseased samples [and information] out of populations like this so we are focusing our eggs into some of these endogamous groups, because in principle what is true for these groups is true for the [general] population," Bhattacharjee said.
According to Bhattacharjee, Parabase is initially targeting the NICU because it is "the nearest neighbor" to the well-baby nursery.
While the company believes its test can help NICU infants, it eventually hopes to be able to prevent some children from ever having to enter the NICU by offering Lifetime for widespread newborn screening.
"A couple of things will have to happen, [though,] before the test can be used for newborn screening," he said. "The first step may be more voluntary – some couples who know about [the test] may opt for it. But to move it to full newborn screening will require more [work and considerable effort.]"
"The big problem with WGS in asymptomatic babies is if you apply that to all babies, they are all going to turn out to be abnormal. Genomes have variations [and many are variants we have no clue about.]"
Targeted testing is relatively easier in this respect, he said. "But you will not be able to get a $1,000 test adopted as newborn screening, especially worldwide. That's half of some countries' GDP."
"If price goes down another order of magnitude … at that point, the pressure would be nothing to switch -- that's what current newborn screening costs [in some instances in the US]," he said.