Cost-efficient whole genome-sequencing using novel mostly natural sequencing-by-synthesis chemistry and open fluidics platform
Level 5 - mechanism / opinion, no new human data
Technological validation and bench platform development (level assigned by design analogy).
OpenAlex W4281715053 · doi:10.1101/2022.05.29.493900
What was done
The authors evaluated a novel sequencing platform combining an open flow cell design on a circular wafer with mostly natural nucleotides without reversible terminators. System performance was benchmarked via whole-genome sequencing across seven Genome-In-A-Bottle reference samples (HG001-7) to assess base accuracy, single-nucleotide polymorphism accuracy, and insertion-deletion accuracy in homopolymers. Scalability was assessed by sequencing 224 additional samples from the 1000 Genomes Project.
What was found
The platform demonstrated read lengths of approximately 300 bp, run times under 20 hours, base accuracy of Q30 > 85%, and sequencing cost of $1/Gb. In the reference samples, SNP accuracy was 99.6% and indel accuracy in homopolymers up to length 10 was 96.4% across >98% of high-confidence regions. High concordance was reported for the 224 samples from the 1000 Genomes Project, though specific numerical concordance metrics were not detailed in the abstract.
Why it matters
This work presents a low-cost alternative chemistry and open-fluidics hardware platform for high-throughput whole-genome sequencing without relying on standard reversible terminators.
Limits
Testing was limited to standard reference samples rather than diverse primary clinical samples. Accuracy in difficult or repetitive regions outside the >98% high-confidence benchmark regions was not reported. The abstract does not report specific quantitative concordance statistics for the 224 population samples.
Cited by
- supports The cost of whole genome sequencing has dropped from approximately one billion dollars historically to around $300.