Computational Advances in Genome and Transcriptome Using HiFi Sequencing

PacBio HiFi sequencing has been used to generate the latest and most complete version of the human genome, characterize population-level structural variations, diplotype pharmacogenetic loci, and elucidate complex alternative splicing at the single-cell level. The two main characteristics of HiFi data – long read length and high accuracy – are critical for applications that either require near-perfect consensus sequencing or long-range phasing information. However, existing computational tools that were designed for short-reads often failed to either utilize the long-range information or employed heuristics that did not apply to HiFi data. Thus, a new generation of alignment, assembly, splicing, and annotation tools had to be developed to support the advent of HiFi data.