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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Summary: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).
ISSN:2056-7944