Recent advances in long-read sequencing (LRS) and assembly algorithms have made it possible to generate highly complete telomere-to-telomere (T2T) genome assemblies for humans, animals, plants and other eukaryotes. This promises to usher in a new era in genomics research. However, producing a genome assembly at T2T quality remains expensive and technically challenging. There is a need for ongoing development to improve the affordability of data production, increase the range of usable sample types, and reliably resolve the most challenging genome regions.
Here, I will describe a new genome assembly strategy inspired by the Streets CornettoTM, a much-loved ice-cream once marketed as having ‘no boring bits’. Under our Cornetto paradigm, the genome assembly process is coupled to Oxford Nanopore’s adaptive sequencing functionality, with sequencing target regions iteratively updated to focus LRS data production onto the challenging, unsolved regions of a nascent assembly. This minimises data generation on the genome’s ‘boring bits’ in order to streamline and improve the production of T2T assemblies.
My talk will outline the Cornetto assembly strategy and present benchmarking experiments in which we find strong improvements in assembly quality and production costs, both for human individuals and non-human species (including a range of reptiles, birds and fish). I will show how Cornetto assembly enables production of T2T quality genomes from challenging sample types like human saliva, for the first time. Finally, I will present examples of targeted assembly of medically relevant loci at the very extremes of the genome, to demonstrate how these capabilities can be used to improve the understanding and diagnosis of genomic diseases.