How SPRQ-Nx enables affordable long-read whole genome sequencing without added complexity

 

Long-read whole genome sequencing is starting to show up in places it rarely could before. With the introduction of SPRQ-Nx, HiFi sequencing has now become the most affordable long-read sequencing technology to date. This revolutionary development is prompting many researchers to ask: with long reads at nearly the same cost as short reads, why not attain the most complete and accurate genomes with HiFi?

Newly released WGS datasets generated with SPRQ-Nx put that question into practice by showing how affordability and data quality coexist across human, plant, and animal genomes. The release includes the well-studied HG002 human genome alongside a curated set of plant and animal genomes chosen for their range of size and complexity. Together, these datasets show that lowering the cost of long-read sequencing does not require sacrificing data quality or changing workflows.

 

How SPRQ-Nx saves up to 40% in reagent costs

SPRQ-Nx is an update to HiFi sequencing chemistry that lowers the cost per genome by enabling SMRT Cell reuse. With SPRQ-Nx, a single SMRT Cell can support multiple sequencing runs, reducing reagent cost per genome by up to 40 percent compared to the current SPRQ iteration. As low as $300 per human genome and roughly $100 per 1 Gb genome at scale, HiFi genome costs are approaching those of short reads while delivering deeper insights through more complete characterization of the genome and integrated epigenome.

This improved affordability is what makes scaling HiFi sequencing more accessible. Instead of reserving long read WGS for a small number of samples, SPRQ-Nx allows projects to expand in size while maintaining consistent, excellent performance. As projects grow, the economics of HiFi sequencing allow that scale without disrupting established experimental approaches.

 

Lower genome costs built into existing workflows

The value of SPRQ-Nx comes from pairing chemistry performance with more efficient use of sequencing consumables. By performing multiple runs on the same SMRT Cell, labs can reduce per genome sequencing costs without adding steps or operational burden.

Importantly, this is effectively the same workflow. Library preparation stays the same, instrument interactions stay the same, and data analysis pipelines remain unchanged. SMRT Cells stay on the instrument and are managed by software, with automatic washing and handling built in. This chemistry update improves access to HiFi sequencing while keeping the day-to-day user experience unchanged.

 

SPRQ-Nx shows reliably high quality human whole genomes

The HG002 human dataset highlights how SPRQ-Nx performs in a well-benchmarked WGS context. The dataset includes 8 runs across 4 SMRT Cells and shows that SPRQ-Nx delivers consistent performance across uses, and matches or exceeds the yield and quality of the popular SPRQ chemistry. SPRQ-Nx demonstrates excellent performance at 20x for SNVs, indels, and structural variants as well.

 

 

 

 

Genome assembly quality is similarly consistent. Assemblies generated across uses show comparable contiguity and completeness, reinforcing that reuse does not introduce variability in data quality. This level of repeatability is especially important for population scale studies and benchmarking efforts where uniformity across samples matters.

 

Consistent multiomic performance across reuse

In addition to sequence and variants, the inclusion of kinetic analysis of modified bases to detect methylation markers automatically brings a multiomic perspective to every HiFi run with no extra treatment, equipment, or cost. In addition to more established epigenetic signals like 5mC and 6mA, SPRQ-Nx additionally enables detection of 5hmC as part of the same experiment, adding an additional epigenetic dimension without requiring changes to sample preparation or sequencing workflows.

SPRQ-Nx maintains detection of these epigenetic signals across SMRT Cell reuse, with comparable 5mC and 6mA performance across uses, matching expectations from standard HiFi workflows. Fiber-seq results also remain highly reproducible between uses, with stable chromatin architecture patterns and consistent detection of accessibility features.

 

Affordable plant and animal WGS with SPRQ-Nx

The plant and animal datasets extend this demonstration across multiple species, including meadowfoam, sea otter, spotted owl, and rice, using SPRQ-Nx across repeated SMRT Cell uses.

Across all four species, SPRQ-Nx delivers consistent yield and accuracy between uses, with performance comparable to SPRQ benchmarks. Assemblies show strong contiguity relative to genome size and complexity, and coverage remains stable across runs. Together, these datasets show that SMRT Cell reuse supports high quality WGS across a wide range of biological contexts.

 

 

Expanding access to long-read whole genome sequencing

SPRQ-Nx expands who can use HiFi sequencing and the types of projects it can support, making larger studies more practical and easier to plan. With increased scale, long-read data can be incorporated earlier in population-level projects rather than reserved for follow-up analysis. As these datasets grow in size, diversity, and multiomic richness, they also become more valuable for downstream work, both linking variants to phenotype and training AI models to understand the genome. What will you do with SPRQ-Nx?

 

Explore the SPRQ-Nx datasets

Want to see it for yourself? Explore the datasets and join the upcoming SPRQ-Nx webinar.