bioRxivGenomicsPreprint
Cost-efficient whole genome-sequencing using novel mostly natural sequencing-by-synthesis chemistry and open fluidics platform
Gilad Almogy, Mark Pratt, Florian C. Oberstrass, Linda LeeiD, Dan Mazur, Nate Beckett, Omer BaradiD, Ilya Soifer, Eddie Perelman, Yoav Etzioni, Martin Sosa, April Jung, Tyson A. ClarkiD, Eliane H. Trepagnier, Gila Lithwick‐YanaiiD, Sarah R. PollockiD, Gil Hornung, Maya LevyiD, Matthew Coole, Tom Howd, Megan ShandiD, Yossi FarjouniD, James Emery, Giles HalliD, Sam LeeiD, , Doron LipsoniD
Abstract
We introduce a massively parallel novel sequencing platform that combines an open flow cell design on a circular wafer with a large surface area and mostly natural nucleotides that allow optical end-point detection without reversible terminators. This platform enables sequencing billions of reads with longer read length ([~]300bp) and fast runs times ( 85%), at a low cost of $1/Gb. We establish system performance by whole-genome sequencing of the Genome-In-A-Bottle reference samples HG001-7, demonstrating high accuracy for SNPs (99.6%) and Indels in homopolymers up to length 10 (96.4%) across the vast majority (>98%) of the defined high-confidence regions of these samples. We demonstrate scalability of the whole-genome sequencing workflow by sequencing an additional 224 selected samples from the 1000 Genomes project achieving high concordance with reference data.
- organism: human
- assay: whole-genome sequencing
- research focus: variant calling
- approach: experimental assay
Abstract summary
Claude Opus 5.5 · xhigh effort · 18 Oct 2026 · from the abstract · CC BY-NC-ND 4.0
Open flow cell on a circular wafer with mostly natural nucleotides and no reversible terminators: about 300 bp reads at $1/Gb, 99.6% SNP accuracy on reference human genomes.
Sequencing cost and read length govern how widely whole genomes can be sequenced. This platform reads incorporation by optical end-point detection with mostly natural nucleotides, without reversible terminators, on an open large-area circular-wafer flow cell, at a reported cost of $1/Gb and read length around 300 bp.
Key results
ShownWhole-genome sequencing of the Genome-In-A-Bottle reference samples reached high small-variant accuracy, including for insertions and deletions inside homopolymer runs.
On samples HG001-7: 99.6% accuracy for SNPs and 96.4% for insertions and deletions in homopolymers up to length 10, covering more than 98% of the samples' defined high-confidence regions. · Abstract
ClaimedThe platform is reported to deliver billions of reads at read length around 300 bp and a cost of $1/Gb.
Stated as platform capability enabled by the open circular-wafer flow cell and terminator-free chemistry; no run-level throughput table, instrument time or comparison with other platforms is given in the abstract. · Abstract
ClaimedThe whole-genome workflow was run at a larger scale on population-genomics samples and reported to agree closely with existing reference calls.
224 further samples selected from the 1000 Genomes Project were sequenced; the concordance with reference data is asserted without a percentage, variant class breakdown or discordance analysis. · Abstract
Methods, data and reproducibility
A massively parallel sequencing-by-synthesis platform built on an open flow cell on a large-surface circular wafer, using mostly natural nucleotides so that base incorporation is detected optically at end point rather than through reversible terminators; performance was established by whole-genome sequencing of reference samples and then a larger panel of population samples.
- Genome-In-A-Bottle reference samples sequenced to whole-genome depth for accuracy benchmarking · human · n = HG001-7
- selected samples from the 1000 Genomes Project sequenced to test workflow scalability · human · n = 224
- Methods & tools
- sequencing-by-synthesis, Genome-In-A-Bottle (GIAB) reference samples, 1000 Genomes Project
Limitations (2)
- Accuracy is quoted only within the high-confidence regions defined for the reference samples, so behaviour in the harder remainder of the genome is not addressed. · noted in this summary
- No head-to-head comparison with an established sequencing platform is reported, and the concordance on the 224 population samples carries no number. · noted in this summary
Read this if you commission large-scale human whole-genome sequencing and want the accuracy and cost profile of a terminator-free chemistry.
- Citations
- 70
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