Table 1.

Advantages and applications of long-read sequencing

Limitations of short read data

Applications and advantages of long-read sequencing

Access to high GC content regions Resolution of complex regions of the genome (e.g. MHCa) Repetitive regions where short reads will not map uniquely Systematic context-specific error modes Structural variation, and large segmental duplications Paralogous regions of the genome Resolution of phase (read-based phasing)

De novo assembly from long reads to span the low complexity and repetitive regions, to create accurate assemblies (3). Targeted sequencing of complex genomic and paralogous regions and resolution of phase for clinical applications e.g. HLAb typing, ADPKDc (4). Transcriptomics, allowing full length sequencing of isoforms and examination of splicing (5). Detection of structural variants (e.g. segmental duplications, gene loss and fusion events) Single molecule sequencing allows examination of clonal heterogeneity of pathogens, and immunogenic cells Long-range characterization of methylation patterns

^aMHC: Major histocompatibility complex.

^bHLA: Histocompatibility leucocyte antigen.

^cADPKD: Autosomal-dominant polycystic kidney disease.