PacBio’s Pink Desktop Platform, $500 Genome Chemistry
By Allison Proffitt
November 7, 2024 | This week at the American Society of Human Genetics meeting, Pacific Biosciences unveiled both its new SPRQ chemistry—pronounced “spark”— and its newest sequencing platform, Vega, a desktop, long-read sequencer with all the compute on board. Also it’s pink.
The color is on brand, of course, but it’s also symbolic, Pacific Biosystems’ CEO Christian Henry told Bio-IT World earlier this week. “It’ll stand out in the lab, but it won’t be obnoxious,” he said. “It fits the instrument really well because it is… a very friendly instrument. You can come right up to it,” he said. “There’s virtually no training required to get runs started.”
Beyond the color, Vega and SPRQ both represent a new philosophy for PacBio, said Henry, who has been at the helm of PacBio since September 2020, but served on the company’s board since 2018. “PacBio historically built one product for the market. They would launch a product and then start working on the next product, which would be a direct replacement for the prior product,” Henry told Bio-IT World. “This serial development path really is difficult… you alienate certain classes of customers that perhaps can’t afford your offering.”
This week’s new product announcements, Henry said, “build a portfolio of sequencers that reach different kinds of customers, whether they’re capital constrained or they want the best running cost, all with the highest data quality possible [and] the maximum amount of interoperability between the different systems.”
Little Pink Box
It was clear to Henry that PacBio needed an instrument with, “a substantially lower capital cost so that we could get into all of the core labs, the smaller diagnostic labs, for example.” Vega aims to meet those needs: a $169,000 HiFi long-read sequencing platform for the benchtop.
Vega miniaturizes many components of Revio, Henry said, and uses the same SMRT cells, though only one per run. He reports R-squared values between Revio and Vega data of .996. “Our customers are going to be very confident that what they sequence on Vega is the same as what they could sequence on Revio,” he said.
Vega exchanges throughput for its smaller footprint. A 24-hour run generates 600 full-length RNA samples per year using the Kinnex full-length RNA kit, 9,600 samples using the PureTarget repeat expansion panel, or 200 human genomes. Henry noted that users can set up a second run about halfway through the first.
Henry expects Vega to serve the needs of a new customer base, including clinical settings where it may be used by technicians without a lot of genomics experience. Whole isoforms and transcriptomics are ideal applications for this long-read sequencing, Henry said, and Vega will perform really well for users of PacBio’s PureTarget panels of 20 hard-to-sequence genes that are clinically important. Henry expects diagnostics companies to jump at the opportunity to use Vega and the PureTarget panels to, “basically eliminate some of the old processes that they’ve been using like capillary electrophoresis and long-range PCR.” Customers have been buying Revio platforms to do that work thus far; Henry said such diagnostics have been a driver for Revio sales this year.
PacBio is now accepting orders for Vega systems, which it plans to begin shipping in the first quarter of 2025.
Spark Chemistry
While PacBio announced both Vega and the new SPRQ chemistry at ASHG, the two don’t yet work together. The new SPRQ chemistry instead represents an iteration for the Revio platform, Henry said, and the culmination of 18 months of R&D work. “In the long run, we want Revio to really have a long life and create more value for customers,” Henry said.
The SPRQ advance that Henry is most excited about is reduced DNA input requirements—from 2 micrograms to 500 nanograms—a four-fold improvement over the most recent requirements.
“This is important because it enables all kinds of different samples that could never get to Revio, never get to long-read sequencing to be able to be used and sequenced on our platform,” he said. “That’s going to open up the door to millions of samples that perhaps we couldn’t get to in the past.”
SPRQ also increases throughput by 33% per SMRT cell. “Now we can offer two whole genomes per run,” Henry said. Each Revio instrument can sequence up to 2,500 human whole genomes per year at a cost of just under $500 per human genome. “If you’re a high-volume user, you likely have a much better price than that,” Henry added.
In addition, a SMRT Link and instrument software upgrade paired with the release of SPRQ chemistry provides new DNA methylation callers that greatly increase the multiomics capabilities of every Revio run. The software brings improved accuracy for calling 5mC, making HiFi sequencing an attractive alternative to methylation arrays. “We haven’t quite had the best-in-class methylation caller, but now we’ve made some significant enhancements in our ability to call, and the algorithms that we use,” Henry said. “We do think it’s perhaps best-in-class in terms of its ability to call methyl.”
SPRQ also adds a new capability to call 6mA, which is used as a marker of open chromatin in the Fiber-seq assay, providing DNA, methylation, and chromatin accessibility all from a single DNA input and sequencing run.
The SPRQ chemistry and SMRT Link software are available for order starting immediately and will begin shipping in December 2024.
SPRQ chemistry is compatible with existing SMRT cells and any Revio system after a software update. SPRQ chemistry is not yet available for Vega, but Henry expects it will be, over the course of 2025, offering an “upgrade path” for Vega users. “Vega will likely get more powerful over the course of time,” he said.
“Historically, the sequencing market has been, there’s a technology and you have to try to fit every application into that technology. And my belief is that… different applications are going to require different technologies,” Henry said. “Meeting the customer where they are has to be a core tenant of what we’re trying to accomplish.”