Attending the Advances in Genome Biology and Technology (AGBT) meeting in June 2022 in Orlando, FL, was like drinking from a firehose of genomic information. Or rather, two firehoses. The first let loose a steady stream of information about progress in spatial biology. Speakers shared their excitement over new discoveries, and exhibitors included established companies that were intent on consolidating their positions, as well as newcomers determined to carve out their own niches. Attendees could not escape the multicolored images of labeled tissues—from figures neatly positioned on posters to marketing images splayed across entire walls of the conference center.
The focus on spatial was evident from the beginning of the conference, when two early talks included spatial data. William Hwang, MD, PhD, an assistant professor of radiation oncology at the Massachusetts General Hospital Cancer Center, described how spatial technology is being used to capture interactions among different cell types in treatment-resistant pancreatic cancer. Kevin King, MD, PhD, assistant professor of medicine/cardiology and bioengineering at the University of California, San Diego, discussed how spatial technology is being used to survey infarct and border zones in ischemic heart disease.
The other hose? New next-generation sequencing (NGS) technologies. Several new NGS platforms, including those developed by Singular Genomics, Element Biosciences, and Ultima Genomics, made entrances that could put pressure on Illumina. Indeed, James Hadfield, PhD, a genomics expert and the senior director of epigenomics, Oncology Translational Medicine, AstraZeneca, tweeted, “2022 could be as important as 2006.”
Which new technologies will stay afloat in a flooded NGS market? That remains to be seen. For new NGS companies, rising with the tide will become all the more challenging as veteran companies continue to innovate. (Illumina has introduced the Infinity and Chemistry X platforms, and Pacific Biosciences (PacBio) has developed new, highly accurate, short-read sequencing capabilities). One thing is certain—the entire NGS field is overflowing with new technology.
The 900-person conference, held a stone’s throw from Walt Disney World, was opened by Eric Green, MD, PhD, director of the National Human Genome Research Institute (NHGRI). Green said that AGBT meetings, which started in 2000, help establish the rhythm of the science of genomics because they register how technologies are coupled with scientific advances. The meetings, he explained, timestamp the announcements and launches that move the field in “seismic ways.”
Besides all the serious science, the AGBT meetings offer showmanship. This year’s meeting was no different. It was full of splashy talks and company swag. Here, GEN dispenses with the glitz to offer an inside look into the technologies, the talks (both the scripted on-stage statements and the casual off-stage chatter), and the genomics community’s interactions that made up the substance of “AGBT week” in Florida this year.
Advances in sequencing technology
In the run-up to AGBT, it was apparent to many genomics insiders that Element Biosciences, a silver sponsor, would be the new kid on the block. The company held a virtual launch in March because of AGBT’s COVID-19-induced postponement. (The meeting was originally scheduled for February 2022.) In addition, Element resolved to make a splash whenever AGBT was finally held. And finally, the company did make a splash, describing post-launch advances and future plans.
Sheila Dodge, general manager of genomics at the Broad Institute—an early-access user—described her team’s three-week experience as a beta testing group for Element’s AVITI sequencer. She noted that her team was impressed by the two independently operated flowcells. Each had a yield of 130–150 Gb. The Q30 exceeded 90% for all runs, and the average quality score was 39. Dodge noted that the Broad also liked the cost of the AVITI.
Economy is one area where
Element hopes to beat its competitors. Element announced a bundled pricing option: order three AVITIs for just $249K each. But Dodge did point out a couple of areas for improvement: the efficiency with which input is circularized, and the range of analytical services available from cloud vendors.
Element wasn’t the only new company to make a splash at AGBT. There was also a splash from Ultima Genomics. Indeed, the splash made by Ultima was somewhat splashier for having been unexpected. Only one attendee at the meeting told GEN that they had been aware of any specifics about Ultima’s debut at AGBT. It was only one week before the meeting that Ultima was revealed as the third silver sponsor.
NGS aficionados learned about Ultima over Memorial Day weekend, when the company posted four preprints on bioRxiv, including one describing the technology driving the company’s instrument—the UG-100. How does the UG-100 work? According to one of the preprints, the UG-100 utilizes a circular 200-mm silicon wafer as an “open flow-cell.”
“This wafer,” the preprint continues, “is patterned at micron scale generating a dense array of electrostatic landing pads to bind clonally amplified sequencing beads, which are separately produced by an automated emulsion PCR process. A spin-dispense system delivers reagents to the wafer by dispensing reagents from dedicated nozzles near the center of the rotating wafer and distributing the reagents rapidly and uniformly across the wafer by centrifugal force. … Optical measurement of the entire surface is performed during rotation of the wafer in a continuous process, analogous to reading a compact disc.”
This procedure relies on a sequencing chemistry approach Ultima calls mostly natural sequencing by synthesis, or mnSBS: “[Each] sequencing cycle [utilizes] a single base from a mostly natural nucleotide mix, which comprises a minority (<20%) of fluorescently labeled, nonterminated nucleotides and a majority of unlabeled, nonterminated (natural) nucleotides. The resulting synthesized DNA is mostly unmodified, yet incorporated bases can still be efficiently measured at the reaction endpoint via high-throughput optical scanning with a high signal-to-noise ratio.”
The UG-100 will be available to buy next year. This high-throughput sequencer is poised to compete with Illumina’s top-of-the-line NovaSeq.
Everything about Ultima seems big, from its 350 employees to the $600 million it has raised since its very stealthy launch in 2016. Even the size of the UG-100 drew attention. The model on display at the meeting was a very large box (roughly 6 feet tall) that would require at least one other box for sample prep. The UG-100’s size quickly became the fodder for coffee hour chatter, with people joking that it is big enough to fit 500 graduate students inside.
A more reserved presence at the AGBT was maintained by Singular, one of the meeting’s bronze sponsors. The company occupied a somewhat out-of-the-way spot on the 17th floor of the meeting’s hotel venue. But perhaps the company was confident that it could, as the saying goes, build a better mousetrap and have the world beat a path to its door.
In this case, the mousetrap is the G4 instrument, which offers faster run times than the competition and is poised to compete with the AVITI and Illumina’s NextSeq.
Singular announced three advances at AGBT. The first is Max Read (M Series) flow cells for short reads which will offer up to 4 billion reads/run at low prices. Singular also announced two partnerships, one to apply Olink’s sequencing-based proteomic readout to Singular’s max read kits, and another to incorporate TwinStrand Biosciences’ duplex sequencing technology. The latter partnership is meant to bring high-accuracy, high-efficiency sequencing solutions for the monitoring of measurable residual disease in translational research settings.
For its part, Illumina presented some iterative technological advances, including new (and longer) read lengths on the NextSeq P1 flowcell (2 × 50 bp and 2 × 300 bp). But details regarding the company’s mysterious “Chemistry X” project, which was announced at the J.P. Morgan Health Care Conference in January 2022, remained elusive.
Jonas Korlach, PhD, the chief scientific officer of PacBio, announced the company’s new short-read technology. Called “sequencing by binding,” or SBB, it is not to be confused with “sequencing by synthesis,” or SBS, the core technology found in Illumina’s and Element’s sequencers. PacBio acquired the short-read chemistry, which has an accuracy higher than that of its competitors, when it acquired Omniome. The platform does not have a name yet, or a price tag.
China’s MGI Tech (MGI) opted to issue a press release on the eve of the conference. The news, which had all the portent of a storm warning, was that MGI’s CoolMPS sequencing chemistry and instruments became commercially available in the United States last August. These medium-high-throughput sequencers are just the beginning for MGI coming stateside.
MGI was expected to reveal additional details about its launch plans when it participates in the American Society of Human Genetics conference in October. These plans—which pertain to the availability of library prep kits for whole genome sequencing, whole exome sequencing, RNA sequencing, metagenomics sequencing, and more—could change the competitive landscape for NGS veterans and startups alike.
Advances in spatial technology
Single-cell spatial analysis technologies, like characters at Disney World, were around every corner and, at times, hard to differentiate. Despite that, these technologies generated palpable excitement. They allow the ability to study RNA “where Mother Nature put it.” This observation was offered by Joe Beechem, PhD, chief science officer, NanoString Technologies.
There were several spatial veterans at AGBT. Two of them are NanoString and 10x Genomics. Each presented its second spatial platform at AGBT this year. For either company, the first platform was introduced for discovery—looking at large amounts of genes, in large sections of tissues, with lower resolution. Now, each company has a complementary platform to look at fewer genes in more detail. The first allows discovery; the second can dig deeper into specific questions.
NanoString is building off its GeoMx platform, which was launched at AGBT two years ago. Associate director of research, Margaret Hoang, PhD, NanoString’s “NGS guru,” told GEN that it was great to see people excited about spatial. It reminded her of the NGS revolution more than a decade earlier, where even though there were different technologies, everyone knew the importance of high-throughput sequencing.
When NanoString launched the GeoMx, the aim was to look comprehensively at all genes. Now, NanoString is launching the CosMx platform. It analyzes only 1,000 genes, and it can look at subcellular localization. The idea is to get a big picture with the GeoMx and then dig deeper with the CosMx. The CosMx, which will ship later this year, is listed for $295,000 (the same as the GeoMx.)
The pioneers in the single-cell space, 10x Genomics, shared a similar sentiment about reliving the buzz being generated. Michael Schnall-Levin, PhD, co-founder and chief technology officer, says that it was similar in the early days of single-cell omics, but “maybe not the same fever pitch.” For him, the excitement validates that this area is exciting.
10x Genomics was out early with its spatial platform, the Visium, which has been widely adopted. Indeed, more institutions have published results generated on the Visium, to date, than on any other platform. The Visium however, is a low-resolution (not single-cell) system. Now, 10x Genomics is launching the Xenium, which can take a deep dive into 400 genes but should be able to go to 1,000.
The core of Xenium comes from technology that 10x Genomics acquired when it bought the companies Readcoor and Cartana a few years ago. At the time, Schnall-Levin recalls, 10x Genomics had been thinking about building its own high-resolution, single-cell, spatial instrument. The company took parts from Readcoor and Cartana and reinvented them into the Xenium.
For a small company of only 70 employees, Resolve Biosciences, the AGBT meeting’s Gold sponsor, had a big presence. Resolve’s name was visible on everything from chocolates to playing cards. The company’s technology—molecular cartography, which is a combinatorial single-molecule fluorescence in situ hybridization (smFISH)—originated in Germany at Qiagen in 2016. The smFISH technology has been at Resolve’s core since the company began in 2020. (At that time, Qiagen veteran Jason Gammack left Inscripta to co-found Resolve and become the company’s CEO.)
The technology was on full display in the Gold sponsor talk. This talk, which was given by Michael Snyder, PhD, professor in the department of genetics, Stanford University School of Medicine, was entitled, “Context matters: Spatial-temporal subcellular gene expression patterns in systems biology and human cell atlases through spatial genomics.”
It’s hard to find someone more excited about the spatial explosion than Niro Ramachandran, PhD, chief business officer, Akoya Biosciences. He predicts that in a few years, all spatial platforms will have multiomics capabilities, with the ability to run 100–1,000-plex assays, and will support single-cell (or perhaps subcellular) analyses.
Ramachandran’s vision has room for spatial companies of all kinds. It certainly includes the other spatial companies that had a presence at AGBT. These companies included the synthetic aperture optics (SAO)-based Rebus Biosystems, the MERFISH-based Vizgen, and the sequential fluorescence in situ hybridization (seqFISH)-based Spatial Genomics. They also included Veranome Biosystems—a wholly owned subsidiary of Applied Materials that applies the power of semiconductor chips to spatial biology.
Akoya has been, up until recently, known as a protein spatial company. But Akoya’s new system, the PhenoCycler-Fusion, moved squarely into the transcriptomic space with the RNA chemistry the company presented at AGBT. Akoya noted that its system has a faster turnaround than others and already has multiomic (protein and RNA) imaging capabilities.
In both the spatial and sequencing realms, the AGBT meeting lived up to its reputation as the prime venue for industry news and releases. The meeting presented a convergence of exciting new technologies and their applications to the discovery of biology. Were seismic shifts instigated? Time will tell as the genomics community finds new ways to adopt the technologies on display. Until it all plays out, there will be ample discussion, healthy skepticism, and lots of excitement for the future of genomics.