Benchmarking nanopore sequencing and rapid genomics feasibility: validation at a quaternary hospital in New Zealand

Abstract Approximately 200 critically ill infants and children in New Zealand are in high-dependency care, many suspected of having genetic conditions, requiring scalable genomic testing. We adopted an acute care genomics protocol from an accredited laboratory and established a clinical pipeline usi...

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Main Authors: Denis M. Nyaga, Peter Tsai, Clare Gebbie, Hui Hui Phua, Patrick Yap, Polona Le Quesne Stabej, Sophie Farrow, Jing Rong, Gergely Toldi, Eric Thorstensen, Zornitza Stark, Sebastian Lunke, Kimberley Gamet, Jodi Van Dyk, Mark Greenslade, Justin M. O’Sullivan
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:npj Genomic Medicine
Online Access:https://doi.org/10.1038/s41525-024-00445-5
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author Denis M. Nyaga
Peter Tsai
Clare Gebbie
Hui Hui Phua
Patrick Yap
Polona Le Quesne Stabej
Sophie Farrow
Jing Rong
Gergely Toldi
Eric Thorstensen
Zornitza Stark
Sebastian Lunke
Kimberley Gamet
Jodi Van Dyk
Mark Greenslade
Justin M. O’Sullivan
author_facet Denis M. Nyaga
Peter Tsai
Clare Gebbie
Hui Hui Phua
Patrick Yap
Polona Le Quesne Stabej
Sophie Farrow
Jing Rong
Gergely Toldi
Eric Thorstensen
Zornitza Stark
Sebastian Lunke
Kimberley Gamet
Jodi Van Dyk
Mark Greenslade
Justin M. O’Sullivan
author_sort Denis M. Nyaga
collection DOAJ
description Abstract Approximately 200 critically ill infants and children in New Zealand are in high-dependency care, many suspected of having genetic conditions, requiring scalable genomic testing. We adopted an acute care genomics protocol from an accredited laboratory and established a clinical pipeline using Oxford Nanopore Technologies PromethION 2 solo system and Fabric GEM™ software. Benchmarking of the pipeline was performed using Global Alliance for Genomics and Health benchmarking tools and Genome in a Bottle samples (HG002-HG007). Evaluation of single nucleotide variants resulted in a precision and recall of 0.997 and 0.992, respectively. Small indel identification approached a precision of 0.922 and recall of 0.838. Large genomic variations from Coriell Copy Number Variation Reference Panel 1 were reliably detected with ~2 M long reads. Finally, we present results obtained from fourteen trio samples, ten of which were processed in parallel with a clinically accredited short-read rapid genomic testing pipeline (Newborn Genomics Programme; NCT06081075; 2023-10-12).
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publishDate 2024-11-01
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series npj Genomic Medicine
spelling doaj-art-0f5cba6bc8fc49b9ba4e4897f40294f42024-11-10T12:35:53ZengNature Portfolionpj Genomic Medicine2056-79442024-11-019111310.1038/s41525-024-00445-5Benchmarking nanopore sequencing and rapid genomics feasibility: validation at a quaternary hospital in New ZealandDenis M. Nyaga0Peter Tsai1Clare Gebbie2Hui Hui Phua3Patrick Yap4Polona Le Quesne Stabej5Sophie Farrow6Jing Rong7Gergely Toldi8Eric Thorstensen9Zornitza Stark10Sebastian Lunke11Kimberley Gamet12Jodi Van Dyk13Mark Greenslade14Justin M. O’Sullivan15Liggins Institute, The University of AucklandLiggins Institute, The University of AucklandLiggins Institute, The University of AucklandLiggins Institute, The University of AucklandGenetic Health Service New Zealand-Northern Hub, Te Toka TumaiLiggins Institute, The University of AucklandLiggins Institute, The University of AucklandLiggins Institute, The University of AucklandLiggins Institute, The University of AucklandLiggins Institute, The University of AucklandVictorian Clinical Genetics Services, Murdoch Children’s Research Institute, ParkvilleVictorian Clinical Genetics Services, Murdoch Children’s Research Institute, ParkvilleGenetic Health Service New Zealand-Northern Hub, Te Toka TumaiLiggins Institute, The University of AucklandDiagnostic Genetics, Department of Pathology and Laboratory Medicine, Te Toka TumaiLiggins Institute, The University of AucklandAbstract Approximately 200 critically ill infants and children in New Zealand are in high-dependency care, many suspected of having genetic conditions, requiring scalable genomic testing. We adopted an acute care genomics protocol from an accredited laboratory and established a clinical pipeline using Oxford Nanopore Technologies PromethION 2 solo system and Fabric GEM™ software. Benchmarking of the pipeline was performed using Global Alliance for Genomics and Health benchmarking tools and Genome in a Bottle samples (HG002-HG007). Evaluation of single nucleotide variants resulted in a precision and recall of 0.997 and 0.992, respectively. Small indel identification approached a precision of 0.922 and recall of 0.838. Large genomic variations from Coriell Copy Number Variation Reference Panel 1 were reliably detected with ~2 M long reads. Finally, we present results obtained from fourteen trio samples, ten of which were processed in parallel with a clinically accredited short-read rapid genomic testing pipeline (Newborn Genomics Programme; NCT06081075; 2023-10-12).https://doi.org/10.1038/s41525-024-00445-5
spellingShingle Denis M. Nyaga
Peter Tsai
Clare Gebbie
Hui Hui Phua
Patrick Yap
Polona Le Quesne Stabej
Sophie Farrow
Jing Rong
Gergely Toldi
Eric Thorstensen
Zornitza Stark
Sebastian Lunke
Kimberley Gamet
Jodi Van Dyk
Mark Greenslade
Justin M. O’Sullivan
Benchmarking nanopore sequencing and rapid genomics feasibility: validation at a quaternary hospital in New Zealand
npj Genomic Medicine
title Benchmarking nanopore sequencing and rapid genomics feasibility: validation at a quaternary hospital in New Zealand
title_full Benchmarking nanopore sequencing and rapid genomics feasibility: validation at a quaternary hospital in New Zealand
title_fullStr Benchmarking nanopore sequencing and rapid genomics feasibility: validation at a quaternary hospital in New Zealand
title_full_unstemmed Benchmarking nanopore sequencing and rapid genomics feasibility: validation at a quaternary hospital in New Zealand
title_short Benchmarking nanopore sequencing and rapid genomics feasibility: validation at a quaternary hospital in New Zealand
title_sort benchmarking nanopore sequencing and rapid genomics feasibility validation at a quaternary hospital in new zealand
url https://doi.org/10.1038/s41525-024-00445-5
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