The appearance of a preprint over Memorial Day weekend, describing a new next-generation sequencing (NGS) technology, sparked curiosity within the genomic sequencing world. The authors are from Ultima Genomics, a 350-person company with a stealth mode kept tight enough to leave even NGS insiders guessing. Within 24 hours after posting the preprint, Ultima had emerged out of stealth with a claim that could not be missed—the $100 genome has arrived.

Layer in almost $600 million in fundraising, the curiosity had turned into news.

The preprint, “Cost-efficient whole genome-sequencing using novel mostly natural sequencing-by-synthesis chemistry and open fluidics platform,” introduces the technology underlying the company’s platform—the UG 100.

Taken broadly, the preprint noted that “the first implementation of this approach produces approximately 10 billion reads per run, with a turnaround time of under 20 hrs per run for 300 bp reads, and with base quality similar to existing platforms (Q30 >85%), at a price of $1/Gb.”

Ultima’s reads are longer than typical short reads. And, while long reads are gaining prominence in the field, it remains unclear how much of an improvement 300 bp is over 100 bp. Element Biosciences, which launched in March of this year, offers synthetic long reads that are as large as 10 kb or so. This is smaller than the “true” long-reads offered by companies such as Pacific Biosciences and Oxford Nanopore Technologies, but opens up analysis that cannot be achieved with fragments in the hundreds.

The 20-hour turnaround time is fast (the Next-seq takes roughly 48 hours) although not unheard of as Singular’s G4 runs in 19 hours. Ultima’s quality compares with its competitors. But one place where they have differentiated from others is in price, claiming a $1/Gb pricetag. For comparison, Illumina’s NextSeq is $20/Gb and Element’s AVITI is $5/Gb.

Tech at the top

Gilad Almogy, PhD, Ultima’s founder and CEO, is not, however, a geneticist or even a biologist. Almogy’s PhD is from CalTech in applied physics and his undergraduate degree is in mathematics and physics from the Hebrew University in Jerusalem.

Before he founded Ultima in 2016, he was the founder, president, and CEO at Fulfil Solutions—a company that manufactures custom automation robotics systems. He also founded and served as CEO of Cogenra, a company that manufactures economically-viable solar power.

What made Almogy bring his tech background to the world of genomics? On Ultima’s website, he says that he saw firsthand, in the semiconductor industry, “how the relentless drive to scale computing power transformed our lives, enabling applications no one could have ever foreseen.” Ultima, he says, aims to “unleash the same relentless scaling in sequencing, because we hold a deep-seated conviction that boundless genomic information will lead to scientific discoveries and improvements in human health far beyond what anyone can currently imagine.”

The company is not void of people with experience in the genomics world, however. Rob Tarbox, the vice president of Ultima, comes to the company from Genapsys, having spent five years at Illumina, and several years at Life Technologies. He also spent a year or two in marketing at both Berkeley Lights and 10x Genomics. Ultima’s CSO, Doron Lipson, PhD, comes from Foundation Medicine where he developed clinical assays for tissue and liquid biopsies.

Deep pockets

Ultima Genomics has disclosed that its “leading investors” include General Atlantic, Andreessen Horowitz, D1 Capital Partners, Khosla Ventures, Lightspeed Venture Partners, Marius Nacht, aMoon, Playground Global, and Founders Fund.

Nearly all those investors are firms specializing in venture capital and other funding for startups, noted Alex Philippidis, senior business editor at GEN. Nacht, the only individual investor named, is a pioneer cybersecurity entrepreneur who is co-founder and anchor investor of aMoon, a global health technology and life sciences investment fund based in Israel. Of the other investors, two are based in New York (General Atlantic, D1), while four are VC firms based in California’s Silicon Valley (Andreessen Horowitz, Khosla Ventures, Lightspeed, and Playground Global), and one is based in San Francisco (Founders Fund).

Founders Fund sums up its purpose in a “manifesto” that declares: “We invest in smart people solving difficult problems, often difficult scientific or engineering problems.” Founders Fund’s partners include PayPal co-founder Peter Thiel.

Preliminary data

The preprint describing the technology behind the UG 100 was one of four that Ultima posted on bioRxiv over the weekend.

The other three preprints, from collaborations with early access users, showcase the utility of the UG 100 and comparing it to existing technologies. The capabilities of the UG 100 to generate whole genome methylation data of pre-cancerous tissues are described in the preprint, “Ultra high-throughput whole-genome methylation sequencing reveals trajectories in precancerous polyps to early colorectal adenocarcinoma,” done in collaboration with Michael Snyder, PhD, professor of genetics at Stanford University School of Medicine. The work, the authors say, demonstrates the feasibility of generating large high-quality WGMS data using the Ultima platform.

Can the UG 100 be used to generate transcriptomic data? The preprint, “Single cell RNA-seq by mostly-natural sequencing by synthesis” describes how Josh Levin, PhD, senior group leader in the Stanley Center for Psychiatric Research and Klarman Cell Observatory at the Broad and collaborators adapted and benchmarked a “newly developed, mostly-natural sequencing by synthesis method for scRNA-seq.”

The third of the preprints presents a four million cell genome-wide PerturbSeq study. The research, done by the lab of Jonathan Weissman, PhD, member of the Whitehead Institute and HHMI investigator, presents genome-scale Perturb-seq data targeting all expressed genes with CRISPR interference (CRISPRi) across more than 2.5 million human cells. The preprint, titled, “Mapping information-rich genotype-phenotype landscapes with genome-scale Perturb-seq” presents an information-rich genotype-phenotype map

Hitting the beach

Members of the genomics community are busy this week practicing talks, printing posters, booking meetings, and packing luggage, in preparation to arrive in Orlando, FL, next week to attend one of the most notable meetings in the field—Advances in Genome Biology and Technology (AGBT).

Unlikely to be a coincidence, AGBT revealed on their website—on the same day that Ultima came out of stealth—that the company is among the three silver sponsors of the meeting, alongside 10X Genomics and Element Biosciences.

The timing of Ultima’s launch is well planned and their announcement this week has created waves in the community. Given the sponsorship, Ultima Genomics will not only be in attendance at the meeting next week, but they will also have a significant presence with a suite, a one-hour workshop, two additional talks, and several posters. Next week will bring an idea of just how big of a splash they will make in a field that is already full of very choppy waters.

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