Year: 2025
Type: article
Abstract: Advances in long-read sequencing (LRS) and assembly algorithms have made it possible to create highly complete genome assemblies for humans, animals and plants. However, ongoing development is needed to improve accessibility, affordability, and assembly quality and completeness. ‘Cornetto’ is a new strategy in which we use programmable selective nanopore sequencing to focus LRS data production onto the unsolved regions of a nascent assembly. This improves assembly quality and streamlines the process, both for humans and non-human vertebrates. Cornetto enables us to generate highly complete diploid human genome assemblies using only nanopore LRS data, surpassing the quality of previous efforts at a fraction of the cost. Cornetto enables genome assembly from challenging sample types like human saliva. Finally, we obtain accurate assemblies for clinically-relevant repetitive loci at the extremes of the genome, demonstrating valid approaches for genetic diagnosis in facioscapulohumeral muscular dystrophy (FSHD) and MUC1-autosomal dominant tubulointerstitial kidney disease (MUC1-ADTKD). Long-read sequencing enables high-quality genome assemblies, but challenges remain. Here, the authors introduce Cornetto, a method that improves assembly quality, enables genome sequencing from saliva, and accurately resolves medically-relevant repetitive genes.
Source: Nature Communications
Authors: Hasindu Gamaarachchi, Igor Stevanovski, Jillian M. Hammond, Andre L. M. Reis, Melissa Rapadas, Kavindu Jayasooriya, Tonia Russell, Dennis Yeow, Yvonne Hort, Chirag Patel, Andrew J. Mallett, Elaine Stackpoole, Lauren Roman, Luke W. Silver, Carolyn J. Hogg, Louise M. Streeting, Ozren Bogdanovic, Renata Coelho Rodrigues Noronha, Luís Adriano Santos do Nascimento, Adauto Lima Cardoso, Arthur Georges, Haoyu Cheng, Hardip R. Patel, Kishore Raj Kumar, Amali C. Mallawaarachchi, Ira W. Deveson
Institutions: Garvan Institute of Medical Research, UNSW Sydney, The University of Sydney, Concord Repatriation General Hospital, Prince of Wales Hospital, Neuroscience Research Australia, The University of Queensland, Royal Brisbane and Women's Hospital, Townsville Hospital, Institute for Molecular Bioscience, James Cook University, King Edward Memorial Hospital, Commonwealth Scientific and Industrial Research Organisation, University of Tasmania, Institute for Marine and Antarctic Studies, CSIRO Environment, University of New England, Consejo Superior de Investigaciones Científicas, Centro Andaluz de Biología del Desarrollo, Junta de Andalucía, Universidad Pablo de Olavide, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Universidade Federal do Pará, Universidade Estadual Paulista (Unesp), University of Canberra, Yale University, Australian National University, Royal Prince Alfred Hospital
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: Yale University, Queensland Health, National Computational Infrastructure, Neuroscience Research Australia, Australian Government, Commonwealth Scientific and Industrial Research Organisation, University of Tasmania, Danmarks Grundforskningsfond, University of New England, University of New South Wales, University of Sydney, James Cook University, University of Queensland, Curtin University of Technology, University of Canberra, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação Amazônia Paraense de Amparo à Pesquisa, Universidade Federal do Pará, Universidade Estadual Paulista, Junta de Andalucía, Medical Research Council, Australian Research Council, National Health and Medical Research Council, School of Life and Environmental Sciences, Deakin University, Faculty of Medicine and Health, University of Sydney, National Cancer Institute
OpenAlex ID: W4416594244