Queensland Genomics: an adaptive approach for integrating genomics into a public healthcare system

Vidgen, Miranda E.; Williamson, Dayna; Cutler, Katrina; McCafferty, Claire; Ward, Robyn L.; McNeil, Keith; Waddell, Nicola; Bunker, David

doi:10.1038/s41525-021-00234-4

Cited by 16 publications

(18 citation statements)

References 31 publications

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“…The successful implementation of a precision medicine pipeline into clinical practice requires a robust patient-proximal model incorporating a timely analysis of each patient’s specific actionable genomic aberrations (typically identified through WES). Using the identification of genetic aberrations to tailor personalized patient care has become increasing popular, however, it is important to understand if this is able to be incorporated into healthcare systems and be utilized as a platform for the broader community ( 46 ). The molecular screening and therapeutics (MoST) trial is currently investigating the feasibility of incorporating molecular screening to assist in informing patient management ( 47 ).…”

Section: Genomic Sequencing For Personalized Therapeutic Optionsmentioning

confidence: 99%

Patient-Derived Explants as a Precision Medicine Patient-Proximal Testing Platform Informing Cancer Management

et al. 2021

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Precision medicine approaches that inform clinical management of individuals with cancer are progressively advancing. Patient-derived explants (PDEs) provide a patient-proximal ex vivo platform that can be used to assess sensitivity to standard of care (SOC) therapies and novel agents. PDEs have several advantages as a patient-proximal model compared to current preclinical models, as they maintain the phenotype and microenvironment of the individual tumor. However, the longevity of PDEs is not compatible with the timeframe required to incorporate candidate therapeutic options identified by whole exome sequencing (WES) of the patient’s tumor. This review investigates how PDE longevity varies across tumor streams and how this is influenced by tissue preparation. Improving longevity of PDEs will enable individualized therapeutics testing, and thus contribute to improving outcomes for people with cancer.

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Section: Genomic Sequencing For Personalized Therapeutic Optionsmentioning

confidence: 99%

Patient-Derived Explants as a Precision Medicine Patient-Proximal Testing Platform Informing Cancer Management

et al. 2021

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“…), a joint Australian National Health and Medical Research Council and European Union collaborative research grant (GNT1195743 to L.C. ), a Queensland Genomics project grant ( Vidgen et al 2021 ) and a National Health and Medical Research Council Ideas grant (2012286 to P.H., I.A., A.G., C.F., R.F., S.S., E.S., L.C., S.Y.C.T., E.M., and W.P.). Models were run on graphical processing units supported by the Linkage Infrastructure, Equipment and Facilities (LIEF) at the high-performance computing facility hosted at the University of Melbourne (LE170100200; Lafayette et al 2016 ).…”

Section: Acknowledgmentsmentioning

confidence: 99%

Phylodynamic Inference of Bacterial Outbreak Parameters Using Nanopore Sequencing

Steinig

Duchêne

Aglua

et al. 2022

Molecular Biology and Evolution

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Nanopore sequencing and phylodynamic modelling have been used to reconstruct the transmission dynamics of viral epidemics, but their application to bacterial pathogens has remained challenging. Cost-effective bacterial genome sequencing and variant calling on nanopore platforms would greatly enhance surveillance and outbreak response in communities without access to sequencing infrastructure. Here, we adapt random forest models for single nucleotide polymorphism (SNP) polishing developed by Sanderson and colleagues (2020) to estimate divergence and effective reproduction numbers (Re) of two methicillin-resistant Staphylococcus aureus (MRSA) outbreaks from remote communities in Far North Queensland and Papua New Guinea (n = 159). Successive barcoded panels of S. aureus isolates (2 x 12 per MinION) sequenced at low-coverage (> 5x - 10x) provided sufficient data to accurately infer genotypes with high recall when compared with Illumina references. Random forest models achieved high resolution on ST93 outbreak sequence types (> 90% accuracy and precision) and enabled phylodynamic inference of epidemiological parameters using birth death skyline models. Our method reproduced phylogenetic topology, origin of the outbreaks, and indications of epidemic growth (Re > 1). Nextflow pipelines implement SNP polisher training, evaluation, and outbreak alignments, enabling reconstruction of within-lineage transmission dynamics for infection control of bacterial disease outbreaks on portable nanopore platforms. Our study shows that nanopore technology can be used for bacterial outbreak reconstruction at competitive costs, providing opportunities for infection control in hospitals and communities without access to sequencing infrastructure, such as in remote northern Australia and Papua New Guinea.

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“…ES was funded by Queensland Genomics (41) and a joint PRISM2 & HOT North (NHMRC 1131932) pilot grant (42); ES, CH, EM were funded by a SERTA grant from Townsville University Hospital (2018_21); LC was supported by an NHMRC grant (NHMRC GNT1195743); PH, IA, AG, CF, RF, SS, ES, LC, SYCT, EM, WP were funded by a National Health and Medical Research Council Ideas grant (NHMRC 2012286)…”

Section: Acknowledgmentsmentioning

confidence: 99%

Genomic neighbor typing for bacterial outbreak surveillance

Steinig

Pitt

Aglua

et al. 2022

Preprint

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Genomic neighbor typing enables heuristic inference of bacterial lineages and phenotypes from nanopore sequencing data. However, small reference databases may not be sufficiently representative of the diversity of lineages and genotypes present in a collection of isolates. In this study, we explore the use of genomic neighbor typing for surveillance of community-associated Staphylococcus aureus outbreaks in Papua New Guinea (PNG) and Far North Queensland, Australia (FNQ). We developed Sketchy, an implementation of genomic neighbor typing that queries exhaustive whole genome reference databases using MinHash. Evaluations were conducted using nanopore read simulations and six species-wide reference sketches (4832 - 47616 genomes), as well as two S. aureus outbreak data sets sequenced at low depth using a sequential multiplex library protocol on the MinION (n = 160, with matching Illumina data). Heuristic inference of lineages and antimicrobial resistance profiles allowed us to conduct multiplex genotyping in situ at the Papua New Guinea Institute of Medical Research in Goroka, on low-throughput Flongle adapters and using multiple successive libraries on the same MinION flow cell (n = 24 - 48). Comparison to phylogenetically informed genomic neighbor typing with RASE on the dominant outbreak sequence type suggests slightly better performance at predicting lineage-scale genotypes using large sketch sizes, but inferior performance in resolving clade-specific genotypes (methicillin resistance). Sketchy can be used for large-scale bacterial outbreak surveillance and in challenging sequencing scenarios, but improvements to clade-specific genotype inference are needed for diagnostic applications. Sketchy is available open-source at: https://github.com/esteinig/sketchy

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Queensland Genomics: an adaptive approach for integrating genomics into a public healthcare system

Cited by 16 publications

References 31 publications

Patient-Derived Explants as a Precision Medicine Patient-Proximal Testing Platform Informing Cancer Management

Patient-Derived Explants as a Precision Medicine Patient-Proximal Testing Platform Informing Cancer Management

Phylodynamic Inference of Bacterial Outbreak Parameters Using Nanopore Sequencing

Genomic neighbor typing for bacterial outbreak surveillance

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