Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
734
result(s) for
"Taylor, Jenny"
Sort by:
Are whole-exome and whole-genome sequencing approaches cost-effective? A systematic review of the literature
Purpose
We conducted a systematic literature review to summarize the current health economic evidence for whole-exome sequencing (WES) and whole-genome sequencing (WGS).
Methods
Relevant studies were identified in the EMBASE, MEDLINE, Cochrane Library, EconLit and University of York Centre for Reviews and Dissemination databases from January 2005 to July 2016. Publications were included in the review if they were economic evaluations, cost studies, or outcome studies.
Results
Thirty-six studies met our inclusion criteria. These publications investigated the use of WES and WGS in a variety of genetic conditions in clinical practice, the most common being neurological or neurodevelopmental disorders. Study sample size varied from a single child to 2,000 patients. Cost estimates for a single test ranged from $555 to $5,169 for WES and from $1,906 to $24,810 for WGS. Few cost analyses presented data transparently and many publications did not state which components were included in cost estimates.
Conclusion
The current health economic evidence base to support the more widespread use of WES and WGS in clinical practice is very limited. Studies that carefully evaluate the costs, effectiveness, and cost-effectiveness of these tests are urgently needed to support their translation into clinical practice.
Journal Article
Challenging the third sector : global prospects for active citizenship
The third sector, or the voluntary, civic sector of society, is taking on increasing prominence in the face of retrenchment, austerity, and decreasing confidence in government. This book is the first to offer an up-close look at the relationship between active citizenship and civil society and how that relates to third-sector activities. Drawing on a wide range of theory and case studies, the book explores questions of social connectedness, changing forms of political engagement, and the increasing complexity of the social and environmental problems that the third sector confronts. It will be invaluable for theorists, scholars, and organizers.
Book
Hyperon production and interaction studies in protonproton scattering with HADES
Hyperons and their interactions with baryonic matter may play a key role in our understanding of the core of neutron stars. Moreover, the internal structure of hyperons and their excitations are of great interest. Their structure can be probed by exploiting their couplings to radiative probes such as by measuring electromagnetic transition form factors. HADES (High-Acceptance Di-Electron Spectrometer) at GSI collected high-statistics proton-proton scattering data in 2022 at √s = 3.48 GeV. The Λ - Λ interaction is currently being studied in this data along with production of Σ states where the Dalitz decay of hyperons might be observed for the first time. In addition, the reaction pp → pK + K + Ξ − [π − Λ[ p π − ]] has been studied to probe the production mechanism of double strangeness near its production threshold. This proceeding addresses the hyperon physics case and discusses the ongoing Ξ − analysis. A preliminary upper limit for the cross section at √s = 3.48 GeV is presented taking into account only statistical uncertainties.
Journal Article
The complete costs of genome sequencing: a microcosting study in cancer and rare diseases from a single center in the United Kingdom
Purpose
The translation of genome sequencing into routine health care has been slow, partly because of concerns about affordability. The aspirational cost of sequencing a genome is $1000, but there is little evidence to support this estimate. We estimate the cost of using genome sequencing in routine clinical care in patients with cancer or rare diseases.
Methods
We performed a microcosting study of Illumina-based genome sequencing in a UK National Health Service laboratory processing 399 samples/year. Cost data were collected for all steps in the sequencing pathway, including bioinformatics analysis and reporting of results. Sensitivity analysis identified key cost drivers.
Results
Genome sequencing costs £6841 per cancer case (comprising matched tumor and germline samples) and £7050 per rare disease case (three samples). The consumables used during sequencing are the most expensive component of testing (68–72% of the total cost). Equipment costs are higher for rare disease cases, whereas consumable and staff costs are slightly higher for cancer cases.
Conclusion
The cost of genome sequencing is underestimated if only sequencing costs are considered, and likely surpasses $1000/genome in a single laboratory. This aspirational sequencing cost will likely only be achieved if consumable costs are considerably reduced and sequencing is performed at scale.
Journal Article
Clinical utilisation of a rapid low-pass whole genome sequencing technique for the diagnosis of aneuploidy in human embryos prior to implantation
Background The majority of human embryos created using in vitro fertilisation (IVF) techniques are aneuploid. Comprehensive chromosome screening methods, applicable to single cells biopsied from preimplantation embryos, allow reliable identification and transfer of euploid embryos. Recently, randomised trials using such methods have indicated that aneuploidy screening improves IVF success rates. However, the high cost of testing has restricted the availability of this potentially beneficial strategy. This study aimed to harness next-generation sequencing (NGS) technology, with the intention of lowering the costs of preimplantation aneuploidy screening. Methods Embryo biopsy, whole genome amplification and semiconductor sequencing. Results A rapid (<15 h) NGS protocol was developed, with consumable cost only two-thirds that of the most widely used method for embryo aneuploidy detection. Validation involved blinded analysis of 54 cells from cell lines or biopsies from human embryos. Sensitivity and specificity were 100%. The method was applied clinically, assisting in the selection of euploid embryos in two IVF cycles, producing healthy children in both cases. The NGS approach was also able to reveal specified mutations in the nuclear or mitochondrial genomes in parallel with chromosome assessment. Interestingly, elevated mitochondrial DNA content was associated with aneuploidy (p<0.05), a finding suggestive of a link between mitochondria and chromosomal malsegregation. Conclusions This study demonstrates that NGS provides highly accurate, low-cost diagnosis of aneuploidy in cells from human preimplantation embryos and is rapid enough to allow testing without embryo cryopreservation. The method described also has the potential to shed light on other aspects of embryo genetics of relevance to health and viability.
Journal Article
Hiding in plain sight: a partial deletion of BRCA1 exon 7 undetectable by MLPA is a Nepali founder variant
The family is of Nepali ancestry and there is a positive family history, with three females in the previous generation diagnosed with early-onset breast cancer. The primary analysis, performed in mid-2019, focused on 10 genes linked to familial breast cancer (PanelApp V.1.13: ATM, BRCA1, BRCA2, CHEK2, PALB2, PTEN, RAD51C, RAD51D, STK11, TP53), but no likely-pathogenic variants were identified. First submission relates to two clients, but neither provided ancestry information. Following the generation of GS data, the variant took ~3.5 years to be uncovered, lengthening the family’s diagnostic odyssey and delaying opportunities for cascade screening in at-risk family members.
Journal Article
Recommendations for clinical interpretation of variants found in non-coding regions of the genome
Background
The majority of clinical genetic testing focuses almost exclusively on regions of the genome that directly encode proteins. The important role of variants in non-coding regions in penetrant disease is, however, increasingly being demonstrated, and the use of whole genome sequencing in clinical diagnostic settings is rising across a large range of genetic disorders. Despite this, there is no existing guidance on how current guidelines designed primarily for variants in protein-coding regions should be adapted for variants identified in other genomic contexts.
Methods
We convened a panel of nine clinical and research scientists with wide-ranging expertise in clinical variant interpretation, with specific experience in variants within non-coding regions. This panel discussed and refined an initial draft of the guidelines which were then extensively tested and reviewed by external groups.
Results
We discuss considerations specifically for variants in non-coding regions of the genome. We outline how to define candidate regulatory elements, highlight examples of mechanisms through which non-coding region variants can lead to penetrant monogenic disease, and outline how existing guidelines can be adapted for the interpretation of these variants.
Conclusions
These recommendations aim to increase the number and range of non-coding region variants that can be clinically interpreted, which, together with a compatible phenotype, can lead to new diagnoses and catalyse the discovery of novel disease mechanisms.
Journal Article
Sequencing of human genomes with nanopore technology
Whole-genome sequencing (WGS) is becoming widely used in clinical medicine in diagnostic contexts and to inform treatment choice. Here we evaluate the potential of the Oxford Nanopore Technologies (ONT) MinION long-read sequencer for routine WGS by sequencing the reference sample NA12878 and the genome of an individual with ataxia-pancytopenia syndrome and severe immune dysregulation. We develop and apply a novel reference panel-free analytical method to infer and then exploit phase information which improves single-nucleotide variant (SNV) calling performance from otherwise modest levels. In the clinical sample, we identify and directly phase two non-synonymous de novo variants in
SAMD9L
, (OMIM #159550) inferring that they lie on the same paternal haplotype. Whilst consensus SNV-calling error rates from ONT data remain substantially higher than those from short-read methods, we demonstrate the substantial benefits of analytical innovation. Ongoing improvements to base-calling and SNV-calling methodology must continue for nanopore sequencing to establish itself as a primary method for clinical WGS.
Nanopore sequencing technology generates longer reads than current technologies, but with more errors. Here, the authors develop new analytical tools to improve accuracy and evaluate the potential of nanopore sequencing for clinical human genomics.
Journal Article
Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples
The accurate interpretation of variation in Mendelian disease genes has lagged behind data generation as sequencing has become increasingly accessible. Ongoing large sequencing efforts present huge interpretive challenges, but they also provide an invaluable opportunity to characterize the spectrum and importance of rare variation.
We analyzed sequence data from 7,855 clinical cardiomyopathy cases and 60,706 Exome Aggregation Consortium (ExAC) reference samples to obtain a better understanding of genetic variation in a representative autosomal dominant disorder.
We found that in some genes previously reported as important causes of a given cardiomyopathy, rare variation is not clinically informative because there is an unacceptably high likelihood of false-positive interpretation. By contrast, in other genes, we find that diagnostic laboratories may be overly conservative when assessing variant pathogenicity.
We outline improved analytical approaches that evaluate which genes and variant classes are interpretable and propose that these will increase the clinical utility of testing across a range of Mendelian diseases.
Journal Article