Targeted sequencing and iterative assembly of near-complete genomes
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).
Authors
- Amali Mallawaarachchi (ORCID: https://orcid.org/0000-0002-1229-1701)
- Jillian M. Hammond (ORCID: https://orcid.org/0000-0002-4045-4571)
- Andrew John Mallett (ORCID: https://orcid.org/0000-0002-8752-2551)
- Igor Stevanovski (ORCID: https://orcid.org/0000-0002-7713-1979)
- Arthur Georges (ORCID: https://orcid.org/0000-0003-2428-0361)
- Adauto Lima Cardoso (ORCID: https://orcid.org/0000-0002-7287-5039)
- Melissa Rapadas (ORCID: https://orcid.org/0000-0002-4900-2838)
- Luke W. Silver (ORCID: https://orcid.org/0000-0002-1718-5756)
- Haoyu Cheng (ORCID: https://orcid.org/0000-0002-9209-5793)
- Luís Adriano Santos do Nascimento (ORCID: https://orcid.org/0000-0001-9947-4078)
- Elaine Stackpoole
- Hasindu Gamaarachchi (ORCID: https://orcid.org/0000-0002-9034-9905)
- Chirag Patel (ORCID: https://orcid.org/0000-0002-6374-5224)
- Yvonne Hort
- Carolyn J. Hogg (ORCID: https://orcid.org/0000-0002-6328-398X)
- Kishore Raj Kumar (ORCID: https://orcid.org/0000-0003-3482-6962)
- Louise M. Streeting (ORCID: https://orcid.org/0000-0002-1663-0010)
- Ira W. Deveson (ORCID: https://orcid.org/0000-0003-3861-0472)
- Renata Coelho Rodrigues Noronha (ORCID: https://orcid.org/0000-0001-9150-8544)
- Ozren Bogdanović (ORCID: https://orcid.org/0000-0001-5680-0056)
- Dennis Yeow (ORCID: https://orcid.org/0000-0001-7534-7007)
- Hardip R. Patel (ORCID: https://orcid.org/0009-0007-9509-1257)
- Andre L. M. Reis (ORCID: https://orcid.org/0000-0002-7300-1157)
- Tonia Russell
- Kavindu Jayasooriya
- L. J. Roman
Institutions
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (BR)
- Australian National University (AU)
- CSIRO Oceans and Atmosphere (AU)
- The University of Sydney (AU)
- University of Tasmania (AU)
- Australian Research Council (AU)
- Garvan Institute of Medical Research (AU)
- The University of Queensland (AU)
- University of Canberra (AU)
- Royal Brisbane and Women's Hospital (AU)
- Royal Prince Alfred Hospital (AU)
- Concord Repatriation General Hospital (AU)
- Townsville Hospital (AU)
- King Edward Memorial Hospital (AU)
- UNSW Sydney (AU)
- Yale University (US)
- St Vincent's Hospital Sydney (AU)
- Prince of Wales Hospital (AU)
- Centro Andaluz de Biología del Desarrollo (ES)
- St Vincent's Clinic (AU)
- ARC Centre of Excellence for Innovations in Peptide and Protein Science (AU)
- Universidade Federal do Pará (BR)
- Neuroscience Research Australia (AU)
- James Cook University (AU)
- Universidade Estadual Paulista (Unesp) (BR)
- University of New England (AU)
- Junta de Andalucía (ES)
- Universidad Pablo de Olavide (ES)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-11-24
- DOI
- https://doi.org/10.1038/s41467-025-65410-x
- Citations
- 1
- Primary Topic
- Genomics and Phylogenetic Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.81
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
- 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