Cost-efficient whole genome-sequencing using novel mostly natural sequencing-by-synthesis chemistry and open fluidics platform

Almogy, G.; Pratt, M.; Oberstrass, F.; Lee, L.; Mazur, D.; Beckett, N.; Barad, O.; Soifer, I.; Perelman, E.; Etzioni, Y.; Sosa, M.; Jung, A.; Clark, T.; Lithwick-Yanai, G.; Pollock, S.; Hornung, G.; Levy, M.; Coole, M.; Howd, T.; Shand, M.; Farjoun, Y.; Emery, J.; Hall, G.; Lee, S. K.; Sato, T.; Magner, R.; Low, S.; Bernier, A.; Gandi, B.; Stohlman, J.; Nolet, C.; Donovan, S.; Blumenstiel, B.; Cipicchio, M.; Dodge, S.; Banks, E.; Lennon, N.; Gabriel, S.; Lipson, D.

doi:10.1101/2022.05.29.493900

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bioRxiv · 10.1101/2022.05.29.493900

Cost-efficient whole genome-sequencing using novel mostly natural sequencing-by-synthesis chemistry and open fluidics platform

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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 (<20hrs) with high base accuracy (Q30 > 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.

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Almogy, G., Pratt, M., Oberstrass, F., Lee, L., Mazur, D., Beckett, N., Barad, O., Soifer, I., Perelman, E., Etzioni, Y., Sosa, M., Jung, A., Clark, T., Lithwick-Yanai, G., Pollock, S., Hornung, G., Levy, M., Coole, M., Howd, T., Shand, M., Farjoun, Y., Emery, J., Hall, G., Lee, S. K., Sato, T., Magner, R., Low, S., Bernier, A., Gandi, B., Stohlman, J., Nolet, C., Donovan, S., Blumenstiel, B., Cipicchio, M., Dodge, S., Banks, E., Lennon, N., Gabriel, S., Lipson, D.. 2022-05-30. Cost-efficient whole genome-sequencing using novel mostly natural sequencing-by-synthesis chemistry and open fluidics platform. https://doi.org/10.1101/2022.05.29.493900

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