The Long and Short of It: PacBio Gives Updates on Separate New Long-Read, Short-Read Platforms

October 26, 2022

By Allison Proffitt 

October 26, 2022 | At the American Society of Human Genetics meeting last night, Pacific Biosciences planned to host a “celebration of genomics” Mark Van Oene, PacBio’s Chief Operating Officer, told Bio-IT World in a pre-briefing—sadly without a live Maroon 5 track as is planned for the event. “We’re hoping this really does enable the genomics community,” Van Oene said.  

Among the enabling announcements, PacBio will give updates on its two new sequencing platforms: the Onso Sequencing System, a benchtop short-read DNA sequencing platform entering beta testing; and the Revio long-read sequencing system, for which the company began taking orders last night.  

PacBio Coming Up Short 

The Onso short-read platform uses the sequencing-by-binding (SBB) chemistry that PacBio acquired with Omniome in July 2021. With this announcement, Van Oene said, PacBio is sharing an update on the performance the company is seeing with the Onso system.  

He reports that the Onso platform will support 500 million reads per run and offer 200 and 300 cycle kits enabling paired and single-end reads. For accuracy, Van Oene said, “We’re still expecting this to be a Q40 sequencer—at least 90% of the bases at Q40 or above,” he said, referring to a Phred quality score for the sequencing. Q40 aligns with a 1 in 10,000 probability of an incorrect base call, or 99.99% accuracy.  

“We continue to make advancements on pushing that accuracy up even further past Q40, which is really exciting,” he said, while admitting that we are not even quite sure yet what that level of accuracy can accomplish. “We’re seeing excitement in plants, and animals, and microbes; we’re seeing a lot of excitement in oncology applications. We really do think this will enable oncology as a primary choice of applications.”   

PacBio announced three beta testing sites for the Onso Sequencing System: The Broad Institute of MIT and Harvard, Corteva Agriscience, and Weill Cornell Medicine. Thus far, those beta testers have sent samples to PacBio, and “a couple have already come into our offices and labs to run their own samples and give us some feedback,” Van Oene said. PacBio plans to ship platforms to beta testers’ own labs in the “coming weeks”.  

It’s early, Van Oene conceded, but he maintained that the platform is performing well with impressive accuracy, and the commercialization timeline is on track. PacBio expects to begin taking orders for Onso in the first quarter of 2023 and expects to begin shipments of the system in the first half of 2023. Onso’s list price will be $259,000 per system.  

“We still have six-eight months before first commercial ship next year, and we’re at a point where we can start to get some really good insight from some of these different labs for different applications and sample types,” he said.  

HiFi Happenings 

While Onso announcements are “updates”, Van Oene called Revio, the “big news” of the week. Revio is PacBio’s new HiFi sequencing platform which promises to dramatically increase the scale of long-read studies, decrease the prices, and let users “really start to go after large opportunities for long-read sequencing applications and really start to transform the world of human genomics as it pertains to whole genomics sequencing.”  

The innovation lies in a new SMRT Cell, Van Oene said. “We’ve increased the density of zero-mode waveguides from eight million ZMWs on the current Sequel IIe product to 25 million ZMWs in the same surface area on Revio.” This gives the equivalent of a full 30x human genome per SMRT Cell, Van Oene said, and each SMRT Cell is priced under $1,000.  

Revio includes compute improvements as well—namely the incorporation of NVIDIA GPUs, providing a 20-fold increase in computing power compared to the Sequel IIe system. Van Oene points out at the GPU-powered platform can process four of the new SMRT Cells at once, “the equivalent of 100 million ZMWs sequencing single molecules of long-read DNA.” That output, he adds, gets users to 1,300 genomes per year.  

In addition to providing accelerated basecalling to meet Revio’s higher throughput, the AI-enabled compute will integrate deep learning algorithms to detect DNA methylation from standard sequencing libraries, and DeepConsensus, a deep learning method developed with Google Health to improve the yield and accuracy of HiFi sequencing. 

Not everything is new. The HiFi chemistry itself hasn’t changed; library prep and infrastructure are the same. Yet the new scale and algorithms, PacBio believes, will drive further insights beyond just small variants and insertions/deletions, to include phased sequencing, structural variants, tandem repeats, centromeres and telomeres, and epigenetics.  

PacBio began taking public orders for the Revio yesterday, but Van Oene reported that large customers—Broad, Berry Genomics, and Macrogen officially—have already submitted purchase orders for multiple systems each. PacBio is seeing a shift toward human genetics applications for the HiFi sequencing, he added. “Now the majority of our long-read business is actually in human genetics, and not in plant or animal,” he said. “But both are critical to the success of Revio.”