NEW YORK – Pacific Biosciences has been making good progress as it attempts to enter the short-read sequencing market next year, still dominated by Illumina today.
After acquiring Omniome last year for $800 million, PacBio noted that it planned to develop a new clustering method for use with the firm's sequencing-by-binding (SBB) chemistry.
According to PacBio CEO Christian Henry, who presented at the JP Morgan Healthcare conference on Thursday, the company recently made a breakthrough that improves both read lengths and read accuracy, compared to the emulsion PCR-based method developed by Omniome.
Henry presented data that he said shows the company can get read lengths of up to 200 bp with greater than Q40 accuracy. "Most of the reads are approaching Q50," or one error in every 100,000 bases, he said. "It gives us a lot of confidence we’ll be able to deliver a very high-accuracy, easy-to-use workflow and a powerful sequencer," he said.
The SBB technology also has "mismatch error rates so low, it reaches the true level of variation between the sample and the reference genome," Henry said. In contrast to sequencing-by-synthesis platforms, where the number of mismatch errors goes up as the number of cycles increases, the SBB platform has a flat error profile over all cycles. "Our error rates are so low, we're more than 15 times better than what SBS players can do," he said.
This has implications for oncology sequencing applications, where higher accuracy means fewer false positive variant calls. Thus, customers could either sequence with less coverage, which would lower costs, or sequence even deeper to find otherwise undiscoverable rare variants.
Henry noted that PacBio recently extended its collaboration with Invitae to include an evaluation of its SBB platform in oncology applications. He also disclosed that PacBio has partnered with Canexia Health, a Canadian precision oncology company, though he did not provide any details on that deal.
In addition, Henry revealed the first image of the SBB instrument, a boxy, techno-brutalist design with sharp right angles and a two-tone grey and black color scheme.
As PacBio is moving into short reads, its main rival Illumina is moving into long reads. During the Q&A session, JP Morgan analyst Tycho Peterson asked Henry to react to Illumina's announcement on Monday of a new product, codenamed "Infinity," which it says will offer data on genomic regions up to 10 kb long. Peterson suggested that the technology was acquired by Illumina from Longas Technologies, an Australian startup that developed a "virtual long read" library preparation method that computationally increases read length on short-read next-generation sequencing platforms.
"We've been doing homework to piece together exactly what this is," Henry said, suggesting it is "short reads linked together through sample preparation and software to emulate what a long read would be."
"The challenge is that this has been tried several times and never really gained any traction … you're still fragmenting the DNA and losing information," he said. "It demonstrates that competitors believe long reads are important." He added that applications are "probably more in bacteriology and with smaller genomes."
The idea is reminiscent of Moleculo, and its synthetic long reads, for example, which Illumina acquired in 2013.
In 2022, PacBio hopes to build on a strong year driven by the popularity of its HiFi sequencing protocol. The firm reported preliminary revenues of $130.5 million, up 65 percent year over year. It installed 171 Sequel II or IIe systems, an 84 percent increase from 2020.
It will launch new kits for the Sequel IIe that reduce DNA input requirements and reduce hands-on time. Henry said the company will also release new software this year that allows the instrument to directly call methylated bases on the instrument. "Every sequencing run will be able to call methylation directly, without any additional sample prep or informatics," he said, turning the Sequel IIe essentially into a five-base sequencer.
A partnership with Twist Bioscience will develop target enrichment for HiFi sequencing, and the Broad Institute is developing single-cell RNA isoform sequencing methods to increase the number of reads per run, from approximately 1.6 million to 33 million.
With more than double the number of sales reps than it had at the beginning of 2021, PacBio can push sales in more than 40 countries.