This article has been updated with additional information from Pacific Biosciences.
DENVER – Pacific Biosciences has launched a new benchtop sequencer in a bid to make HiFi long-read sequencing more accessible to potential customers beyond the company's traditional clientele of well-resourced core facilities and genomics labs.
The company unveiled the platform, dubbed Vega, at a launch party in connection with the American Society of Human Genetics annual meeting here on Wednesday night. Despite the cool, stormy weather in Denver, the "Neon Après-ski-themed" party was attended by a sizeable crowd of genomic researchers turned party-goers, who came ready to dance to a live performance by Colorado-based pop rock band OneRepublic following the instrument's launch.
With a listing price of $169,000 and the size of a mini fridge, Vega is intended to help PacBio open the doors to smaller research labs that have not been able to afford its higher-throughput Revio platform, according to the company. Alternatively, researchers can purchase Vega for $79,000 with a reagent commitment for 152 runs. PacBio also said it plans to bring the instrument into the clinical market down the road.
"One of the challenges that we faced is that we haven't had a full portfolio of products, and a lot of customers haven't had the funding to be able to buy a Revio," PacBio CEO Christian Henry told GenomeWeb in an interview. "We wanted to create a system that any lab can afford and get access to HiFi sequencing."
Effectively a miniaturized version of the Revio system, Vega employs the same SMRT cell and existing HiFi workflow for library preparation and data analysis. With one SMRT cell per run, Vega purportedly can analyze 600 full-length RNA samples per year or 200 human genomes, according to PacBio. The sequencing run time remains the same as Revio, which is 24 hours.
According to Henry, one of the major innovations for Vega is the miniaturization of the light pen, a critical component within the sequencer that brings laser light to the SMRT cells for HiFi sequencing. By shrinking the size of the light pen, the company was able to "dramatically reduce" Vega's manufacturing cost while reducing the instrument's overall footprint, he noted.
In addition, new robotics designs and improved basecalling algorithms within Vega all play a role in "significantly" reducing the platform's cost, Henry added.
To make Vega more user-friendly, PacBio also "dramatically simplified" the platform's operational interface, Henry said. The instrument only requires users to handle two consumable components when loading a run: One includes pipette tips and the SMRT cell, while the other contains sequencing reagents and libraries.
"We expect to see more inexperienced or new users of long-read sequencing come to the platform, so we want to make it as easy as possible," Henry noted.
Because of the lower data output, Henry said Vega's per-run sequencing cost will be higher than that of Revio. By his estimate, the sequencing cost of a 20X human genome on the Vega will likely exceed $1,000. At launch, the platform is also not compatible with the new Sprq chemistry, which promises to cut Revio sequencing cost in half, but Henry said the company is working toward making the new chemistry available.
According to Henry, the instrument can be ideal for research applications such as isoform analysis, bacterial genome sequencing, or small-scale human genome studies.
But beyond such research purposes, Henry said PacBio hopes to deploy Vega into the clinical market for applications such as carrier testing, human leukocyte antigen (HLA) typing, and targeted sequencing assays. To that end, the company aims to seek regulatory approval for Vega for diagnostic use, Henry said, though the process will likely take several years.
It remains to be seen how well Vega will fare competitively against nanopore sequencers from Oxford Nanopore Technologies, which have thus far dominated the benchtop long-read sequencing market.
"I think this is a really nice-sized instrument for somebody who wants to get into long-read technologies and doesn't have a large budget," said Anoja Perera, director of sequencing and discovery genomics at the Stowers Institute for Medical Research.
Having installed a Revio platform in July, Perera said her lab is currently not interested in purchasing a Vega platform, but she noted there are some unique features for PacBio versus nanopore sequencing that may make it appealing to researchers. "One thing I love about PacBio is it's very standardized," said Perera, noting that nanopore sequencing, on the other hand, sometimes involves "more trial work" and protocol optimization, which can pose a challenge for a core lab.
At the same time, nanopore sequencing also has its unique advantages, Perera pointed out, such as the ability to perform direct RNA analysis and ultra-long read sequencing, which cannot be achieved by other technologies. As such, her lab also installed a PromethIon 2 Integrated (P2i) system from Oxford Nanopore in recent months.
"I think this is an interesting move," said Alexander Hoischen, a researcher at Radboud University Medical Center in the Netherlands. "It makes the technology more accessible."
A longtime PacBio customer, Hoischen's team currently operates four Revios and is working on validating HiFi whole-genome sequencing (WGS) as a first-line test for rare diseases. While much of his group's efforts have been focused on WGS, Hoischen said, his institution still operates two older PacBio Sequel IIe systems to perform targeted sequencing assays, which amount to 5,000 samples a year.
Covering up to 30 genes, these targeted assays can be powerful in analyzing genes with homologous sequences, which are difficult to profile using short-read Illumina sequencing, he said. Hoischen noted that Vega would also be a great candidate to perform targeted assays, though he said the team "may or may not shift" from the existing Sequel IIe systems.
During ASHG, PacBio also announced that it reduced the listing price for Revio from $779,000 to $599,000. Still, as Vega and Revio have significantly different throughput and cost, Henry believes the two platforms will not compete with each other but rather be complementary. PacBio is currently accepting orders for Vega and will start shipping instruments in the first quarter of 2025.
"My belief is that [Vega customers will] become so excited about long-read sequencing with PacBio and HiFi that over time, as their projects scale, they will switch to Revio," Henry said. "This will certainly be additive to our growth, not subtractive."