NEW YORK – Next-generation sequencing instrument makers went beyond traditional genomics in 2024, integrating new hardware and chemistries to enable multiomics.
In addition to making technological innovations, each NGS firm faced opportunities and challenges against the backdrop of a tough funding environment as well as geopolitical tensions.
Sequencing companies are "finding other growth vectors beyond just core sequencing," said TD Cowen analyst Dan Brennan, who closely follows the field. "I think the sequencer is becoming more of a ubiquitous tool."
Recovering from a tumultuous 2023, Illumina, for instance, made multiomics one of its priorities this year. Soon after it completed its divestment of Grail in June, the company announced the acquisition of single-cell technology firm Fluent BioSciences and integrated that firm's PIPseq instrument-free single-cell sample prep into its product portfolio.
While Illumina maintained that it will remain "an open NGS platform" and will continue to support its existing single-cell partnerships, the Fluent deal puts the firm in direct competition with other single-cell assay developers, such as 10x Genomics, which has optimized its technologies for Illumina sequencing.
In August, Illumina announced the so-called "5-base genome" and "comprehensive WGS" technologies (later branded as constellation mapped read), providing more details at the American Society of Human Genetics annual meeting in November.
The 5-base genome assay detects 5-methylcytosine(5mC) and DNA variants in parallel and will go into early-access testing at the beginning of next year.
Once commercialized, the assay will likely face competition from Biomodal’s epigenetic analysis products, including its Duet Multiomics Solution evoC, which is based on "six-letter seq" technology.
Illumina's constellation mapped read technology, meanwhile, which locates the position of short reads on longer DNA fragments, already has 10 early-access sites, including the Broad Institute, and the company plans to expand early access in the first half of 2025.
Illumina also highlighted its forthcoming proteomics assay at ASHG, developed in partnership with Standard BioTools. Dubbed Illumina Protein Prep, the assay will be able to analyze between 9,000 and 10,000 protein targets when it launches commercially in the first quarter of 2025.
As for PIPseq, Illumina will begin selling kits, which are currently offered by the legacy Fluent team, in the first quarter of 2025.
Illumina also overhauled its mid-throughput MiSeq platform in October. The new MiSeq i100 instrument has a list price of $109,900 and can generate between 5 million and 100 million reads per run, or 3 Gb to 30 Gb of data.
The platform has already gained some traction among researchers. "There are a few really nice features about this instrument such as footprint, ease of use, room temperature reagents, fast run time, etc.," said Anoja Perera, director of sequencing and discovery genomics at the Stowers Institute for Medical Research, whose lab has decided to purchase a MiSeq i100. "We will use this instrument for our amplicon sequencing work plus for small genomes and transcriptomes," she said.
At ASHG, Illumina said it is pushing for longer reads on the MiSeq i100 and is performing 2X500-base runs in its R&D lab.
During 2024, Illumina also lobbied the US Congress for the Biosecure Act, which explicitly targets its Chinese competitors BGI Group and MGI Tech, as well as MGI subsidiary Complete Genomics. The Chinese companies, meantime, separately lobbied against the bill.
First introduced in January by the House Select Committee on Strategic Competition between the United States and the Chinese Communist Party, the Biosecure Act aims to ban federally funded medical providers from using products manufactured or services provided by what it calls "foreign adversary biotech companies of concern."
In May, a new version of the bill extended the deadline to 2032 for existing customers to part way with China-related companies listed in the bill. The US House of Representatives eventually passed the Biosecure Act in September, though many genomics researchers voiced their concerns regarding the legislation.
So far, the US Senate has not formally voted on its version of the legislation, and the chance for the bill to pass before the end of the year is becoming slimmer.
Even if the bill doesn't pass this year, "the majority of investors are planning for this bill to become an eventuality," said Brennan, adding that the Biosecure Act has evidently "really hurt" BGI's and MGI's commercial opportunities in the US.
Still, Complete Genomics held onto the US market while making commercial and technological advancements throughout the year. The company opened a new manufacturing facility in San Jose, California, in the spring, for instance, to product its NGS platforms domestically.
At the Advances in Genome Biology and Technology annual meeting in February, Complete Genomics unveiled a new sequencing platform, DNBseq-G800, that runs the firm's antibody-based CoolMPS chemistry.
In an email, Rob Tarbox, VP of product and marketing, said the company is seeing "more interest" from customers in the G800 platform versus the sibling DNBseq-G400 because of its "longer reads, higher accuracy, and an improved instrument workflow," though he declined to comment on the installed base of either platform.
At ASHG, Complete Genomics also highlighted efforts to bring multiomics and spatial biology capabilities to its sequencing customers. The company has become the exclusive US distributor of products from STOmics Tech, a BGI Group subsidiary that has commercialized the Stereo-seq technology.
Complete Genomics also showcased Go Spatial at ASHG, an automated sample processing platform for Stereo-seq, as well as FluoXpert, which promises to give its DNBSeq-G400 sequencer protein analysis capabilities with a software upgrade.
Also pursuing on-board multiomics capabilities is Element Biosciences, which opened the year by unveiling its new Aviti24 sequencer at the JP Morgan Healthcare Conference in January. Essentially an Aviti platform with hardware and software upgrades, Aviti24 enables in situ analysis of DNA, RNA, proteins, and cell morphology for up to 1.3 million cells per flow cell in a single sequencing run.
In July, Element raised more than $277 million in Series D funding, which will help the firm bring Aviti24 to market and potentially opens an IPO window for the company.
Meanwhile, another NGS newcomer, Singular Genomics Systems, revealed its G4X multiomic platform during this year's AGBT. An upgraded version of its original sequencer, G4X can do direct RNA sequencing, RNA detection, multiplex protein analysis, and digital H&E staining on human tissue sections, including formalin-fixed, paraffin-embedded (FFPE) samples.
In March, Singular cut its workforce by 20 percent due to financial distress, leading the company to pivot to spatial biology applications while deemphasizing its presence in the mid-throughput next-generation sequencing market.
However, things turned brighter for the company later in the year, with rivaling takeover bids from Deerfield Management and Tang Capital Partners, the outcome of which is unclear at present.
For Ultima Genomics, 2024 was a relatively quiet year as the company continued to gain foothold in the high-throughput short-read market dominated by Illumina.
At AGBT, the company fully launched its UG 100 sequencer, revealing several high-profile customers such as the Broad Institute, the New York Genome Center, Exact Sciences, Quest Diagnostics, South Korea's Macrogen, Inocras (formerly known as Genome Insight), and Regeneron.
Throughout the year, Ultima also announced several clinical sequencing partnerships, including one with Quest Diagnostics for minimal residual disease and pediatric rare disease testing, as well as another with Labcorp for cancer testing. At ASHG, Ultima named several certified service providers, such as Macrogen, Inocras, and the University of Minnesota Genomics Center, to make its technology more accessible to researchers.
For the long-read sequencing companies, 2024 was a year of continued technology improvement as the firms tried to expand into the clinical and translational markets.
Pacific Biosciences, which had a tough year financially, is hoping to attract more Revio customers with its new Sprq chemistry, while reducing the instrument's list price from $779,000 to $599,000. Launched at this year's ASHG meeting, Sprq promises to reduce sequencing costs for a 20X HiFi human genome to under $500, half the current cost on the Revio system. Additionally, DNA input decreased fourfold through more efficient sample loading onto the SMRT flow cell.
To entice customers with smaller labs, PacBio also launched a lower-throughput benchtop sequencer, called Vega, during the ASHG meeting. With a list price of $169,000, or $79,000 with a reagent commitment for 152 runs, Vega can purportedly analyze 600 full-length RNA samples per year or 200 human genomes.
For Oxford Nanopore Technologies, the goal for 2024 appeared clear — continuing to expand its presence in the applied, pharmaceutical, and clinical markets.
In May, the UK company announced Ampore-TB, a tuberculosis drug resistance sequencing assay that it expects to become its first in vitro diagnostic test developed in-house. Development of Ampore-TB is spearheaded by Oxford Nanopore Diagnostics, a subsidiary of the company established in 2022.
In addition, Oxford Nanopore forged partnerships with companies and academic institutions this year to expand applications for nanopore sequencing. These include collaborations with Wasatch BioLabs for direct whole-methylome sequencing, Twist Bioscience for pharmacogenomics tests, and Swiss biotech manufacturing firm Lonza for mRNA manufacturing quality control, to name a few.
Oxford Nanopore also encountered a new competitor this year: In August, China's BGI Research, a unit of BGI Group, unveiled its first nanopore sequencer, CycloneSeq. BGI later granted the exclusive rights to commercialize and distribute CycloneSeq globally to its affiliate MGI.
While its remains to be seen how much of a threat CycloneSeq will be to Oxford Nanopore's products, the UK company is already taking legal action. In December, Oxford Nanopore filed a lawsuit in the UK against BGI Group and its affiliates for "breach of contract, misuse of confidential information, and infringement of trade secrets."
Looking ahead to 2025, according to Brennan, there is "probably going to be restructuring" within the National Institutes of Health with the incoming Trump administration, which could potentially negatively impact the NGS tools market. In addition, retaliation from China is likely if the Trump administration decides to impose tariffs on Chinese goods, another risk factor for NGS firms with business in China.