NEW YORK – A year after rolling out its UG 100 high-throughput sequencer, Ultima Genomics announced a number of upgrades to the platform this week that boost data output by 50 percent while reducing costs by 20 percent, allowing customers to sequence a human genome at 30X coverage for as little as $80.
During a company-sponsored workshop at the Advances in Genome Biology and Technology annual meeting on Tuesday, Gilad Almogy, Ultima's founder and CEO, said that the $100 genome the company announced a year ago was "just a start" because of the many "data-hungry applications," such as cancer liquid biopsy testing, transcriptomics, and proteomics projects, where the sequencer serves as a "barcode reader," as well as large-scale whole-genome sequencing programs.
The updated platform, called UG 100 Solaris, combines a number of chemistry, software, and workflow improvements — with no changes to the hardware — that increase its output per wafer to 10 billion to 12 billion reads, reducing cost to $.24 per million reads. This was achieved in part by packing beads more densely onto the wafer, David Peoples, Ultima's chief financial and business officer, told GenomeWeb. As a result, customers can now sequence more than 30,000 human genomes per year on the machine.
Two different workflows are available for the updated version: Solaris Free for PCR-free libraries and Solaris Flex for amplified and converted libraries.
Solaris Free allows users to sequence a human genome at 30X coverage from as little as 2 ng of DNA using the firm's ppmSeq mode, a duplex sequencing method that enables Q60 accuracy for more than 80 percent of single-nucleotide variants. Accuracy for indels, which Almogy said was "not a strong suit when we started," has gone up to 99.81 percent precision.
Solaris Flex is meant for "almost everything else," he said, including single-cell and spatial, proteomics, and epigenetics sequencing applications.
The UG 100 Solaris updates have already been implemented at more than 15 customer sites, including the Broad Institute, and are immediately available to new customers.
In addition, Ultima launched early access for a high-throughput sequencing operating mode called UG 100 Solaris Boost this week that reduces sequencing run times even further, increasing throughput to up to 100 billion reads in 24 hours for certain short-read applications. Solaris Boost will be commercially available later this year.
Niall Lennon, senior director of the Broad Institute's genomics platform and CSO of Broad Clinical Labs, said the Broad Institute has had an early prototype of the Ultima sequencer in-house since 2019 and currently runs two UG 100 machines, which were recently updated to Solaris and routinely produce 10 billion to 12 billion reads per wafer as advertised. Altogether, the Broad has performed more than 1,500 Ultima runs in-house so far.
The Solaris Boost mode, which his team refers to as "beast mode," was just implemented at the Broad for a week and increased throughput from 20 to 32 wafers, he said, without the need for additional personnel. If it was running all the time, weekly throughput could go up to more than 1,000 human genomes at 30X coverage, he added.
In a collaboration with David Reich's group at Harvard, the Broad has embarked on a project to shotgun-sequence 25,000 ancient DNA samples on the Ultima sequencer — a 7.5-trillion-read project. This replaces a targeted hybrid capture approach and lowers costs. "When you have a really sequencing-hungry application, where you just need a lot of reads, having a really high-throughput platform like an Ultima machine allows you to churn through and generate that data in a very easy manner," Lennon said.
Other applications of the Ultima platform at the Broad include an Olink proteome project to discover novel biomarkers for diabetes and heart disease, a single-cell sequencing project for aging profiling, and ppmSeq projects to characterize tumor evolution or anything "where you really need super low error rates to get to the very lowest allele fractions of variant types," he said.
According to Almogy, over the past year, Ultima's sequencing platform has been adopted by a number of labs in the oncology space including Exact Sciences, Inocras, Labcorp, Quest Diagnostics, and Myriad Genetics.
During the workshop, Taylor Jensen, VP and head of oncology science at Labcorp, shared some data from an evaluation of the Ultima platform for possible use in a molecular residual disease (MRD) assay. Such an assay, he said, needs to have high sensitivity and specificity, short turnaround time, and be cost-effective so it can be accessible to patients.
His team first sent cell-free DNA (cfDNA) from noncancerous donors to Ultima for sequencing and subsequently sequenced samples in their own lab in Baltimore using ppmSeq on the UG 100 Solaris platform, finding that Solaris significantly increased coverage and decreased cost per sample. In addition, they compared cfDNA Solaris sequencing data from 30 noncancerous individuals to 111 unique tumor fingerprints, creating 3,300 measurements to assess the platform's analytical specificity. They found that Solaris Free produced low levels of background noise that could potentially be further reduced bioinformatically.
"This gave us a lot of confidence in terms of the specificity that's afforded through ppmSeq and through the Solaris platform, when coupled with that SNVQ60 score and a proprietary, very early, preliminary machine-learning algorithm that we applied here," he said. "As we look towards the future of what our ideal MRD assay should look like, I think that the scalability, the throughput, the cost, and the performance of what we're seeing early in an evaluation of the Solaris platform aligns very well with that vision."
Ultima was also recently chosen as the sequencing technology provider for the UK Biobank Pharma Proteomics Project (UKB-PPP), which is run by a consortium of 14 biopharmaceutical companies and aims to measure 5,400 proteins in 600,000 blood samples from half a million UKB participants. The Regeneron Genetics Center will analyze the samples for the project using the Olink Explore HT affinity proteomics assay and Ultima's sequencing platform.
Chris Whelan, director at Johnson & Johnson Innovative Medicine, provided some insights during the workshop into how the project selected the Ultima platform for sequencing. He said an initial comparison between Illumina and Ultima by both Olink and Regeneron showed that "the correlation between normalized protein expression values generated using Illumina instruments versus the Ultima UG 100 was very high." Additionally, inter-sequencing correlation from Ultima was also very high, "and the precision was virtually identical between Ultima and Illumina."
On cost, the two platform providers were also on par, with "very, very attractive offers from both companies, essentially identical offers in terms of price point," he said. "But what set Ultima apart was that they committed to having a similar economic dynamic for future projects," he added. "So, let's say if we want to work with Our Future Health or FinnGen or another big biobank, Ultima gave a commitment to similar economics."
Finally, Whelan said, some of the pharma companies "felt that competition is good" and would lead to more innovation down the road, tipping the scale toward Ultima, a recent competitor of Illumina.
Besides the UKB-PPP, Ultima is involved in three recent large-scale single-cell endeavors: the Billion Cells Project, a collaboration among the Chan Zuckerberg Initiative, 10x Genomics, and Ultima, which aims to generate a dataset to train AI models; a "100 Million Cell Challenge" grant program run by Scale Biosciences, Nvidia, and Ultima; and Tahoe-100M, a 100-million-single-cell perturbation project in collaboration with Parse Biosciences and Vevo Therapeutics that just released its results as a preprint this week.
Jonah Cool, science program officer at the Chan Zuckerberg Initiative, said during the workshop that "already, the first samples are being sequenced" for the Billion Cells Project.
For sequencing users who don't have high enough sequencing needs to justify bringing an Ultima platform in-house, there is a growing network of service providers available, Almogy said. It now includes Broad Clinical Labs, Eurofins, Inocras, Macrogen, Novogene, Psomagen, the Ontario Institute for Cancer Research, and the University of Minnesota Genomics Center.
"Now, whether you are in the US or in Asia or in Europe, you have access to the best sequencing centers out there, where you can send your samples to be sequenced at extremely low cost," he said. "And does cost matter? Well, I think I heard the word 'NIH' a few times this week, and 'funding.'"