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

Automated library preparation validation with low depth HiFi genome sequencing. Two Miro Canvas instruments were validated using a single SMRTcell of data (∼9× each) with small variant (SNV/indel) benchmarking of NA12878 and fitting results to reference curves defined by manual library preparation of three GIAB reference samples (NA12878, NA24385, NA24631). Error bars represent standard deviations. Automated library preparation results were considered acceptable if Miro Canvas recall (A) and precision (B) values were equivalent or greater than the average manual preparation reference material accuracy results at comparable depths.