Scaled HiFi sequencing for human genomics

HiFi genome sequencing is traditionally performed on single samples per SMRT Cell to generate high coverage sequencing depths. Here we demonstrate multiplex pooling of human samples on single Revio cells to generate long read, low-pass genome sequencing data. We apply this scaled low-pass method to a research cohort of brain samples of ALS controls and positive samples to explore the C9orf72 repeat expansions that are predictive of ALS. Paired with analytics tuned to low-coverage data, this highly scalable approach of multiplex HiFi sequencing can be applied to simultaneously call SNP, indel, and structural variants, highlighting the potential to increase long-read human genome sequencing and analysis throughput by 10-fold.