scholarly journals Diagnosis of D-Bifunctional Protein Deficiency through Whole-Genome Sequencing: Implications for Cost-Effective Care

2015 ◽  
Vol 6 (3) ◽  
pp. 141-146 ◽  
Author(s):  
Alina Khromykh ◽  
Benjamin D. Solomon ◽  
Dale L. Bodian ◽  
Eyby L. Leon ◽  
Ramaswamy K. Iyer ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Cost Effective ◽  
Protein Deficiency ◽  
Whole Genome ◽  
Bifunctional Protein ◽  
Effective Care

scholarly journals Rapid whole-genome sequencing identifies a homozygous novel variant, His540Arg, in HSD17B4 resulting in D-bifunctional protein deficiency disorder diagnosis

2020 ◽  
Vol 6 (6) ◽  
pp. a005496
Author(s):  
Lane Savage ◽  
Stacie D. Adams ◽  
Kiely James ◽  
Shimul Chowdhury ◽  
Surender Rajasekaran ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Protein Deficiency ◽  
Whole Genome ◽  
Bifunctional Protein ◽  
Novel Variant

scholarly journals Using molecular testing and whole-genome sequencing for tuberculosis diagnosis in a low-burden setting: a cost-effectiveness analysis using transmission-dynamic modelling

Thorax ◽  
2021 ◽  
Vol 76 (3) ◽  
pp. 281-291 ◽  
Author(s):  
Tendai Mugwagwa ◽  
Ibrahim Abubakar ◽  
Peter J White
Keyword(s):  
Cost Effectiveness ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Drug Sensitivity ◽  
Cost Effective ◽  
Molecular Testing ◽  
Whole Genome ◽  
Transmission Dynamic ◽  
Sensitivity Testing ◽  
Combined Use

BackgroundDespite progress in TB control in low-burden countries like England and Wales, there are still diagnostic delays. Molecular testing and/or whole-genome sequencing (WGS) provide more rapid diagnosis but their cost-effectiveness is relatively unexplored in low-burden settings.MethodsAn integrated transmission-dynamic health economic model is used to assess the cost-effectiveness of using WGS to replace culture-based drug-sensitivity testing, versus using molecular testing versus combined use of WGS and molecular testing, for routine TB diagnosis. The model accounts for the effects of faster appropriate treatment in reducing transmission, benefiting health and reducing future treatment costs. Cost-effectiveness is assessed using incremental net benefit (INB) over a 10-year horizon with a quality-adjusted life-year valued at £20 000, and discounting at 3.5% per year.ResultsWGS shortens the time to drug sensitivity testing and treatment modification where necessary, reducing treatment and hospitalisation costs, with an INB of £7.1 million. Molecular testing shortens the time to TB diagnosis and treatment. Initially, this causes an increase in annual costs of treatment, but averting transmissions and future active TB disease subsequently, resulting in cost savings and health benefits to achieve an INB of £8.6 million (GeneXpert MTB/RIF) or £11.1 million (Xpert-Ultra). Combined use of Xpert-Ultra and WGS is the optimal strategy we consider, with an INB of £16.5 million.ConclusionRoutine use of WGS or molecular testing is cost-effective in a low-burden setting, and combined use is the most cost-effective option. Adoption of these technologies can help low-burden countries meet the WHO End TB Strategy milestones, particularly the UK, which still has relatively high TB rates.

scholarly journals 807. Same-day Transmission Analysis of Nosocomial Transmission Using Nanopore Whole Genome Sequencing

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S497-S498
Author(s):  
Mohamad Sater ◽  
Remy Schwab ◽  
Ian Herriott ◽  
Tim Farrell ◽  
Miriam Huntley
Keyword(s):  
High Resolution ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Variant Calling ◽  
Cost Effective ◽  
Error Rates ◽  
Sequencing Error ◽  
Snp Analysis ◽  
Whole Genome ◽  
Snp Calling

Abstract Background Healthcare associated infections (HAIs) are a major contributor to patient morbidity and mortality worldwide. HAIs are increasingly important due to the rise of multidrug resistant pathogens which can lead to deadly nosocomial outbreaks. Current methods for investigating transmissions are slow, costly, or have poor detection resolution. A rapid, cost-effective and high-resolution method to identify transmission events is imperative to guide infection control. Whole genome sequencing of infecting pathogens paired with a single nucleotide polymorphism (SNP) analysis can provide high-resolution clonality determination, yet these methods typically have long turnaround times. Here we examined the utility of the Oxford Nanopore Technologies (ONT) platform, a rapid sequencing technology, for whole genome sequencing based transmission analysis. Methods We developed a SNP calling pipeline customized for ONT data, which exhibit higher sequencing error rates and can therefore be challenging for transmission analysis. The pipeline leverages the latest basecalling tools as well as a suite of custom variant calling and filtering algorithms to achieve highest accuracy in clonality calls compared to Illumina-based sequencing. We also capitalize on ONT long reads by assembling outbreak-specific genomes in order to overcome the need for an external reference genome. Results We examined 20 bacterial isolates from 5 HAI investigations previously performed at Day Zero Diagnostics as part of epiXact®, our commercialized Illumina-based HAI sequencing and analysis service. Using the ONT data and pipeline, we achieved greater than 90% SNP-calling sensitivity and precision, allowing 100% accuracy of clonality classification compared to Illumina-based results across common HAI species. We demonstrate the validity and increased resolution of our SNP analysis pipeline using assembled genomes from each outbreak. We also demonstrate that this ONT-based workflow can produce isolate to transmission determination (i.e. including WGS and analysis) in less than 24 hours. SNP calling performance ONT-based SNP calling sensitivity and precision compared to Illumina-based pipeline Conclusion We demonstrate the utility of ONT for HAI investigation, establishing the potential to transform healthcare epidemiology with same-day high-resolution transmission determination. Disclosures Mohamad Sater, PhD, Day Zero Diagnostics (Employee, Shareholder) Remy Schwab, MSc, Day Zero Diagnostics (Employee, Shareholder) Ian Herriott, BS, Day Zero Diagnostics (Employee, Shareholder) Tim Farrell, MS, Day Zero Diagnostics, Inc. (Employee, Shareholder) Miriam Huntley, PhD, Day Zero Diagnostics (Employee, Shareholder)

scholarly journals Very low depth whole genome sequencing in complex trait association studies

2017 ◽  
Author(s):  
Arthur Gilly ◽  
Lorraine Southam ◽  
Daniel Suveges ◽  
Karoline Kuchenbaecker ◽  
Rachel Moore ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Association Studies ◽  
Low Frequency ◽  
Cost Effective ◽  
Complex Trait ◽  
Whole Genome ◽  
Supplementary Data ◽  
Trait Association ◽  
High Depth

AbstractMotivationVery low depth sequencing has been proposed as a cost-effective approach to capture low-frequency and rare variation in complex trait association studies. However, a full characterisation of the genotype quality and association power for very low depth sequencing designs is still lacking.ResultsWe perform cohort-wide whole genome sequencing (WGS) at low depth in 1,239 individuals (990 at 1x depth and 249 at 4x depth) from an isolated population, and establish a robust pipeline for calling and imputing very low depth WGS genotypes from standard bioinformatics tools. Using genotyping chip, whole-exome sequencing (WES, 75x depth) and high-depth (22x) WGS data in the same samples, we examine in detail the sensitivity of this approach, and show that imputed 1x WGS recapitulates 95.2% of variants found by imputed GWAS with an average minor allele concordance of 97% for common and low-frequency variants. In our study, 1x further allowed the discovery of 140,844 true low-frequency variants with 73% genotype concordance when compared to high-depth WGS data. Finally, using association results for 57 quantitative traits, we show that very low depth WGS is an efficient alternative to imputed GWAS chip designs, allowing the discovery of up to twice as many true association signals than the classical imputed GWAS design.Supplementary DataSupplementary Data are appended to this manuscript.

scholarly journals A robust, cost-effective and widely applicable whole-genome sequencing protocol for capripoxviruses

2022 ◽  
pp. 114464
Author(s):  
Elisabeth Mathijs ◽  
Andy Haegeman ◽  
Kris De Clercq ◽  
Steven Van Borm ◽  
Frank Vandenbussche
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Cost Effective ◽  
Whole Genome
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