Analytical validation of germline small variant detection using long-read HiFi genome sequencing.

ABSTRACT: Long-read sequencing has the capacity to interrogate difficult genomic regions and phase variants; however, short-read sequencing is more commonly implemented for clinical testing. Given the advances in long-read HiFi sequencing chemistry and variant calling, we analytically validated this technology for small variant detection (single nucleotide variants, insertions/deletions; SNVs/indels; <50 bp). HiFi genome sequencing was performed on DNA from reference materials and clinical specimen types, and accuracy results were compared to short-read genome sequencing data. HiFi genome sequencing recall and precision across Genome in a Bottle (GIAB)-defined non-difficult and difficult genomic regions (high confidence) for SNVs are >99.9% and >99.7%, respectively, and for indels are >99.8% and >99

SUBMITTER: Hammond N 

PROVIDER: S-EPMC12129021 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature