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Pacific Biosciences Reveals Follow-up Sequencer to Sequel II, Timeline for Short-Read Platform

PacBio Revio sequencer

This story has been updated to include additional information from PacBio, Stacey Gabriel, and Fritz Sedlazeck.

LOS ANGELES — Pacific Biosciences has launched a successor to its Sequel II long-read sequencing instrument, called Revio, that promises higher throughput at lower cost. It also released a timeline for the commercialization of its new short-read sequencing-by-binding platform, named Onso.

Touting a large increase in the density of key technical components, the firm claimed the Revio will soon be able to sequence a human genome at 30X coverage for about $1,000 in sequencing reagent costs.

At a launch party Tuesday night in connection with the American Society of Human Genetics annual meeting, PacBio made Revio the warm-up act for Grammy-winning pop band Maroon 5.

The new instrument will carry over PacBio's HiFi protocol, which distills circular reads to reach accuracy of 99.9 percent. Where it outpaces the Sequel II is in throughput. Improvements to the process by which PacBio manufactures zero-mode waveguides (ZMWs), the nanotechnology features that enable its single-molecule, real-time sequencing method, have led to a threefold increase in density. Each SMRT cell will have approximately 25 million ZMWs, up from 8 million. With each Revio able to run four flow cells independently, that means customers can sequence 1,300 whole genomes per year at 30X coverage for less than $1,000 each.

With the addition of onboard Nvidia graphics processing units to handle the gush of HiFi data, run times on the new instrument will also be shorter, approximately 24 hours, down from about 30 hours. Technicians can also load libraries during the middle of a run, reducing instrument downtime. Overall, PacBio claims a fifteenfold increase in throughput.

PacBio is accepting orders for Revio now and intends to deliver the first instruments, listed at $779,000, in the first quarter of next year. Customers who recently purchased a Sequel II or IIe will be offered special upgrade packages, according to Mark Van Oene, PacBio's chief operating officer.

The company hopes Revio will be loved by the human genetics research community. "It's becoming the biggest market opportunity," for the firm, Van Oene said in an interview prior to the launch. He added that ASHG is "the biggest conference for what PacBio's doing today."

Revio could open up several new sequencing applications for long reads, including rapid sequencing of critically ill newborns and their parents, according to Tomi Pastinen, director of Children's Mercy Hospital's Genomic Medicine Center. The hospital has partnered with PacBio on long-read sequencing for several years. While he's "certainly interested" in the instrument, Pastinen said, his lab has not yet decided to submit a purchase order to replace their Sequel IIe fleet.

"It looks like one would be able to do more real-time patient genomics," he said. "The throughput and lower cost would enable those studies much better than the Sequel IIe would."

HiFi sequencing has driven a boom in long-read sequencing on PacBio instruments over the last several years, and it has proved invaluable for assembling higher-quality, more contiguous genomes. It is the data type of choice for the Human Pangenome Reference Project, and the National Institutes of Health's All of Us research program is processing thousands of genomes using HiFi reads.

In a Wednesday ASHG workshop sponsored by PacBio, Stacey Gabriel, director of the Broad Institute Genomics Platform, noted that her team plans to use lower coverage HiFi sequencing — about 8X to 10X — on 10,000 samples from the All of Us program. 

"For a lot of population genomics or research applications, you can choose the depth of coverage you want," Van Oene said. "It's not always going to be 30X." A lower-coverage HiFi-based genome, which also includes methylation calls, could approach the cost of a 30X short-read genome, he suggested. Coupled with the new throughput capabilities, that could unlock more of the population sequencing market for long reads. 

PacBio is eschewing an early-access program for Revio. "The system is mature enough that we're likely to go through beta testing and get some feedback and go straight into a full commercial launch," Van Oene said, adding that data quality from the instrument is "at least equivalent to what we're getting off the Sequel IIe."

In another workshop presentation on Wednesday, Baylor College of Medicine Professor Fritz Sedlazeck presented fresh data from cell line samples sequenced on Revio by PacBio. "It looks really good," he said, noting that he had received it just a day before. "We'll have to dig into it." Revio produced 51.43 Gb per SMRT Cell, with a mean read lengths of 5.5 kb and mean read quality of Q38, he said. 

Meanwhile, the Onso short-read platform is about to undergo beta testing at the Broad Institute, Corteva Agriscience — a company PacBio partnered with earlier this year to develop new workflows — and Weill Cornell Medicine before starting to ship commercially in the first half of 2023. Onso will launch with two reagent kits: a 200-cycle kit enabling 1x200 bp and 2x100 bp paired-end sequencing and a 300-cycle kit enabling 2x150 bp sequencing. There will also be a conversion kit for existing short-read libraries. PacBio said the Onso platform can generate between 400 million and 500 million clusters per flow cell.

Following the announcement of the Revio and Onso platforms, PacBio said it is withdrawing all prior financial guidance and will provide more information during its third quarter earnings call on Nov. 7. The firm had lowered its full-year revenue guidance this summer in response to weak sales in Europe and China.

Whether launch event attendees had primarily come to see the instrument or the band varied by the individual, but both played to a packed house. "It used to be at this meeting that people were trying to sign up for Illumina events," said Onuralp Soylemez, a rare disease researcher at Brigham and Women's Hospital, who listed Maroon 5 as his favorite band. "Now PacBio becomes the popular one."

This story includes additional reporting by Huanjia Zhang.