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Singular Genomics Developing New Flow Cell Tech to Reduce Cost of Short Reads

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NEW YORK – Singular Genomics Systems, a soon-to-be competitor to Illumina in the short-read sequencing market, is working on new technology to reduce costs for sequencing applications using reads approximately 30 bp to 100 bp long.

"The cost per read doesn't get that much cheaper for short reads versus longer reads" right now, Singular Cofounder and CEO Drew Spaventa told investors on a conference call on Wednesday following the release of the firm's first quarter financial results. "That's a pain point. If someone is doing a 50-base or 70-base read versus a 300-base read, they're not getting a third of the price for that read. It's not even close. So how do you allow people to see real cost savings for short reads? And [that's] the technology we're working on."

The so-called Max Read, or M Series, flow cell could accommodate up to 1 billion reads, "which we think will be a big differentiator for a lot of the short-read applications," including counting-based ones such as noninvasive prenatal testing and single-cell RNA-seq. Max Read is one of several R&D programs that the San Diego-based company continues to work on as it prepares to ship its G4 mid-throughput next-generation sequencer later in the second quarter. The company also continues to improve its sequencing cycle time and has completed an internal study of RNA sequencing on the G4, company officials said.

Singular did not elaborate on how the technology works but said it will discuss Max Read more at next month's Advances in Genome Biology and Technology conference and in a forthcoming technical paper.

The company hopes Max Read can help differentiate its G4 platform, both from Illumina's dominant short-read NGS offerings and from a slew of other new entrants including Element Biosciences, Pacific Biosciences' short-read platform acquired with Omniome, and under-the-radar startups.

The firm remains on track to ship the G4 by the end of the quarter, Singular officials said, and continues to improve the specs on the instrument.

"We improved our cycle time throughout the year last year," Spaventa said, getting it down from around four minutes in early-access testing to under three minutes. The firm is also seeing some F2 flow cells, which are specified to produce 150 million reads each, generate more than 200 million reads.

Singular has also completed an application note for RNA-seq workflows, touting the G4's performance in comparison to Illumina's NextSeq 2000. Using 2X100 bp sequencing, each sample produced 25 million reads on both instruments. Replicate runs of universal human reference RNA samples on the G4 yielded between 37 million and 55 million paired-end reads, with Q30 base quality scores for all replicates exceeding 86 percent.

"The overall comparison was nearly identical across all secondary RNA-seq analysis metrics," Spaventa said, including for transcript counts, number of detected genes at two different expression levels, and read distribution across genic and intergenic regions.

Looking ahead, Spaventa said the company has "demonstrated greater than Q50 accuracy" with 150 bp paired reads and more than 100 million reads per flow cell for its HD-Seq kit for rare variant detection. It has also published data on XR-Seq, a library preparation method to help analyze longer molecules, approximately 1 kb to 3 kb in length, from short-read sequencing data.

In addition, the firm has assembled its first beta PX instruments for spatial, single-cell, and multiomic analysis, he said.

Singular did not immediately respond to requests for comment on when customer data might emerge to support its own internal studies.

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