Ultima Genomics' ppmSeq™ Delivers Unmatched Combination of Sensitivity and Efficiency for Whole-Genome MRD Detection

New bioRxiv paper showcases:

• Tumor-informed ctDNA detection down to one-in-ten million (10^-7), which extends well beyond the limits of currently available clinical minimal residual disease (MRD) assays
• Superior double-stranded DNA (dsDNA) recovery rates versus other technologies, reducing sequencing requirements by 10- to 100-fold to achieve ultrasensitive detection levels and enabling a cost-effective whole-genome approach
• High efficiency and simple WGS workflow, yielding greater than 20x coverage per ng of cfDNA, reducing the amount of input material required for MRD and other liquid biopsy applications
• New highly sensitive approach to tumor-informed MRD as well as tumor-naive MRD and monitoring settings, where matched tumor tissue is not available

FREMONT, Calif., Aug. 14, 2025 /PRNewswire/ -- Ultima Genomics, a developer and manufacturer of an innovative ultra-high throughput sequencing architecture, announced a new publication, made available today in bioRxiv, showing the ultra-sensitive single-nucleotide variant (SNV) detection capabilities of its ppmSeq^™ technology, with error rates down to 8 x 10^-8. Led by researchers from the Landau Lab at Weill Cornell Medicine and the New York Genome Center, this pre-print also demonstrates ctDNA detection limits for ppmSeq which significantly extends beyond the limits of currently available MRD assays, while utilizing a simple whole genome sequencing workflow that requires 10- to 100-fold less sequencing coverage versus other error correction techniques. These researchers conclude that these key features make ppmSeq well suited for clinical applications where high accuracy is required for mutation identification, such as tumor informed and tumor agnostic MRD detection.

"With its unique combination of low-cost and high accuracy, ppmSeq marks a real breakthrough in sequencing technology," said Dan A. Landau, MD, PhD, a core member at the New York Genome Center, and Professor of Medicine & Professor of Physiology and Biophysics at Weill Cornell Medicine. "It opens new horizons in studying the somatic genome as a novel frontier in human genetics, and holds enormous promise for clinical applications, including sensitive detection of cancer residual disease."

While high-throughput sequencing has seen rapid adoption for genome-wide variant identification, distinguishing true biological variation in the form of SNVs from sequencing errors remains a key challenge. Traditional sequencing approaches are too error-prone for detection of low variant allele frequency variants and are blind to errors resulting from DNA degradation or damage during sample preparation. These challenges limit the ability of traditional NGS technologies to detect and identify rare variants, a feature which is important in emerging applications like MRD and somatic mosaicism.

To increase the ability to detect rare variants, current NGS approaches often rely on error-correction techniques, such as duplex sequencing, which involves sequencing both strands of a DNA molecule to filter out errors identified by discordant strands caused by single-stranded damage. While this reduces SNV error rates for dual-stranded reads, singleton reads must be discarded for these methods. As such, these methods require massive over sequencing to reliably capture sufficient duplex molecules, making whole-genome duplex sequencing prohibitively expensive.

In a Nature Methods paper published in 2025, researchers in the Landau Lab demonstrated the advantages of identifying SNVs with Ultima's flow-based sequencing by synthesis technology versus conventional SBS chemistry. Researchers identified that the ultra-low error profiles of Ultima's flow-based sequencing chemistry presented a foundation on which to build error correction techniques using duplex sequencing that could potentially enable ultra-low ctDNA detection levels, meaningful for applications that require rare mutation detection like MRD. 

In this new bioRxiv paper, researchers from the same group utilized ppmSeq, a technology developed by Ultima and native to the Ultima platform, to further improve upon the previously published low SNV detection limits. Building on Ultima's ultra-low error, flow-based sequencing, ppmSeq encodes both strands of DNA molecules in a single sequencing read to enable up to part-per-ten million (10^-7) accuracy (SNVQ70) for SNV calling. This exceptional accuracy provides extreme assay sensitivity for low frequency alleles while also requiring 10- to 100-fold less sequencing depth than other error correction techniques. 

Study showcases ppmSeq as a highly accurate, low-cost, high throughput method for dsDNA sequencing built on a simple WGS workflow with potential for robust clinical applications

Researchers from the Landau Lab at Weill Cornell Medicine and the New York Genome Center benchmarked ppmSeq assay performance and sensitivity against other technologies. Key findings demonstrate ppmSeq has:

1. Ultrasensitive SNV detection capabilities. ppmSeq demonstrated ultrasensitive SNV detection with error rates down to 0.8 x 10^-7 (0.8 parts-per-ten million) for gDNA and cell-free DNA.
2. Superior dsDNA recovery rates and lower sequencing requirements. ppmSeq demonstrated superior double-stranded DNA (dsDNA) recovery rates, reducing sequencing requirements by 10- to 100-fold and enabling a cost-effective whole genome approach.
3. Ability to sequence low-input samples. The ppmSeq workflow was shown to be highly efficient, yielding greater than 20x coverage per ng of cfDNA and reducing the amount of input material required.

Researchers also tested the capabilities of ppmSeq in clinical applications by assessing circulating tumor DNA (ctDNA) detection for disease monitoring in cancer patients. Key findings include:

1. Tumor-informed ctDNA detection down to one-in-ten million. ppmSeq enabled tumor-informed ctDNA detection of 10^-5 across multiple cancers, and up to 10^-7 in cancers with high mutation burden at 30x sequencing depth, which extends below the limits of current MRD assays.
2. ctDNA detection capabilities in tumor-naive disease monitoring. ppmSeq identified disease-specific signal in plasma cell-free DNA without the need for a matched tumor.

Together, these researchers conclude that ppmSeq is a highly accurate and cost-effective option for emerging clinical applications including tumor-informed MRD, tumor-naïve MRD and an opportunity to explore new whole-genome applications in cancer genomics, including somatic mosaicism.

"As a highly accurate, highly scalable WGS approach, ppmSeq can be a key building block for the next generation of tumor-informed and tumor-naive cancer monitoring applications" said Adam Widman, MD, a researcher and medical oncologist at Memorial Sloan Kettering Cancer Center and a co-author on the study.

"ppmSeq is a major step forward in high-accuracy sequencing," said Charles Swanton, Deputy Clinical Director at The Francis Crick Institute. "Its low error rate and high throughput could enable powerful new applications in liquid biopsy and beyond. This study showcases how ultra-low error, high-throughput sequencing with ppmSeq could transform applications in the field of MRD requiring very high accuracy — from bench to bedside."

Ultima's ppmSeq technology enables high-quality data and its published specifications provide part-per-million accuracy, or SNVQ60, for calling single nucleotide variants (SNVs). ppmSeq, designed for the UG 100 sequencing platform, is also compatible with the UG 100 Solaris Free workflow. Launched at AGBT 2025, the UG 100 Solaris workflows enabled an over 50% increase versus prior specifications in output to 10 to 12 billion reads per wafer and pricing reduced by 20% to $0.24 per million reads, enabling the $80 genome.

"Ultima's unique sequencing architecture was designed to specifically meet the needs of cost-effective, large-scale applications. It especially excels in applications like liquid biopsy that require extreme accuracy, and we are excited to see further validation of ppmSeq within the academic community," said Gilad Almogy, CEO and Founder of Ultima Genomics. "We believe that sensitivity, ease of workflow and low cost of ppmSeq will be transformational for applications requiring earlier detection such as MRD."

The full study, "Paired plus-minus sequencing is an ultra-high throughput and accurate method for dual strand sequencing of DNA molecules" is now available in bioRxiv.

About Ultima Genomics

Ultima Genomics is unleashing the power of genomics at scale. The Company's mission is to continuously drive the scale of genomic information to enable unprecedented advances in biology and improvements in human health. With humanity on the cusp of a biological revolution, there is a virtually endless need for more genomic information to address biology's complexity and dynamic change—and a further need to challenge conventional next-generation sequencing technologies. Ultima's revolutionary new sequencing architecture drives down the costs of sequencing to help overcome the tradeoffs that scientists and clinicians are forced to make between the breadth, depth and frequency with which they use genomic information. The new sequencing architecture was designed to scale far beyond conventional sequencing technologies, lower the cost of genomic information and catalyze the next phase of genomics in the 21st century. To learn more, visit www.ultimagenomics.com

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