Short read shotgun sequencing has infiltrated nearly all genomics research programs thanks its expansive depth of coverage and great accuracy. However, its technical shortcomings leave several aspects of genomics unresolved, such as the extend and impact of complex structural variations and repetitive regions on genome biology.
The advent of long read sequencing promises to resolve these shortcomings. Once stigmatised for its high error-rate, Oxford nanopore technologies can produce ultra long reads while detecting base modifications, in real time. As read lengths greater than 100kb are becoming increasingly routine, we can observe entire chunks of native human chromosomes at single nucleotide resolution. Here, we illustrate how ultra-long reads can shed light into macrogenomics by exposing the sequence components of chromothrypsis-derived neochromosomes, hyper-methylated regions, and the first megabase long sequencing read.
With regards to nanopore's base calling error-rate, we relate how signal-level algorithms can lead to highly accurate sequence analysis, such as single cell barcode demultiplexing. By venturing into ‘squiggle space’, we describe how electronic signal from nanopore sequencers can be harnessed to increase the amount of de-multiplexed full length cDNA sequences from 10X Chromium single-cell sequencing by more than 2-fold. The unique nature of nanopore sequencing, and the bioinformatics opportunities it presents, mark an exciting new era for genomic research.