ORCID Profile
0000-0002-7436-8727
Current Organisations
University of Oxford
,
University of Bristol
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Publisher: F1000 Research Ltd
Date: 25-01-2021
DOI: 10.12688/WELLCOMEOPENRES.16157.2
Abstract: Deep sequencing of the full-length hepatitis B virus (HBV) genome provides the opportunity to determine the extent to which viral ersity, genotype, polymorphisms, insertions and deletions may influence presentation and outcomes of disease. Increasing experience with analysis of HBV genomic data opens up the potential for using these data to inform insights into pathophysiology of infection and to underpin decision making in clinical practice. We here set out to undertake whole genome HBV sequencing from an adult who presented acutely unwell with a new diagnosis of HBV infection, and tested positive for both HBV anti-core IgM and IgG, possibly representing either acute hepatitis B infection (AHB) or chronic hepatitis B with an acute reactivation (CHB-AR). The distinction between these two scenarios may be important in predicting prognosis and underpinning treatment decisions, but can be challenging based on routine laboratory tests. Through application of deep whole-genome sequencing we typed the isolate as genotype-D1, and identified several minority variants including G1764A and G1986A substitutions in the pre-core promoter and pre-core regions, which support CHB-AR rather than AHB. In the longer term, enhanced deep sequencing data for HBV may provide improved evidence to distinguish between acute and chronic infection, to predict outcomes and to stratify treatment.
Publisher: Springer Science and Business Media LLC
Date: 08-05-2019
DOI: 10.1038/S41598-019-43524-9
Abstract: Advancing interventions to tackle the huge global burden of hepatitis B virus (HBV) infection depends on improved insights into virus epidemiology, transmission, within-host ersity, drug resistance and pathogenesis, all of which can be advanced through the large-scale generation of full-length virus genome data. Here we describe advances to a protocol that exploits the circular HBV genome structure, using isothermal rolling-circle lification to enrich HBV DNA, generating concatemeric licons containing multiple successive copies of the same genome. We show that this product is suitable for Nanopore sequencing as single reads, as well as for generating short-read Illumina sequences. Nanopore reads can be used to implement a straightforward method for error correction that reduces the per-read error rate, by comparing multiple genome copies combined into a single concatemer and by analysing reads generated from plus and minus strands. With this approach, we can achieve an improved consensus sequencing accuracy of 99.7% and resolve intra-s le sequence variants to form whole-genome haplotypes. Thus while Illumina sequencing may still be the most accurate way to capture within-s le ersity, Nanopore data can contribute to an understanding of linkage between polymorphisms within in idual virions. The combination of isothermal lification and Nanopore sequencing also offers appealing potential to develop point-of-care tests for HBV, and for other viruses.
Publisher: Microbiology Society
Date: 03-2020
DOI: 10.1099/JGV.0.001387
Publisher: Wiley
Date: 21-02-2018
DOI: 10.1111/JVH.12849
Publisher: F1000 Research Ltd
Date: 14-10-2020
DOI: 10.12688/WELLCOMEOPENRES.16157.1
Abstract: Deep sequencing of the full-length hepatitis B virus (HBV) genome provides the opportunity to determine the extent to which viral ersity, genotype, polymorphisms, insertions and deletions may influence presentation and outcomes of disease. Increasing experience with analysis of HBV genomic data opens up the potential for using these data to inform insights into pathophysiology of infection and to underpin decision making in clinical practice. We here set out to undertake whole genome HBV sequencing from an adult who presented acutely unwell with a new diagnosis of HBV infection, and tested positive for both HBV anti-core IgM and IgG, possibly representing either acute hepatitis B infection (AHB) or chronic hepatitis B with an acute reactivation (CHB-AR). The distinction between these two scenarios may be important in predicting prognosis and underpinning treatment decisions, but can be challenging based on routine laboratory tests. Through application of deep whole-genome sequencing we typed the isolate as genotype-D1, and identified several minority variants including G1764A and G1986A substitutions in the pre-core promoter and pre-core regions, which support CHB-AR rather than AHB. In the longer term, enhanced deep sequencing data for HBV may provide improved evidence to distinguish between acute and chronic infection, to predict outcomes and to stratify treatment.
Publisher: Springer Science and Business Media LLC
Date: 09-02-2018
Publisher: American Society for Microbiology
Date: 15-11-2015
DOI: 10.1128/JVI.02106-15
Abstract: A more comprehensive understanding of hepatitis C virus (HCV) transmission dynamics could facilitate public health initiatives to reduce the prevalence of HCV in people who inject drugs. We aimed to determine how HCV sequences entered and spread throughout Scotland and to identify transmission hot spots. A Scottish data set with embedded demographic data was created by sequencing the NS5B of 125 genotype 1a (Gt1a) s les and 166 Gt3a s les and analyzed alongside sequences from public databases. Applying Bayesian inference methods, we reconstructed the global origin and local spatiotemporal dissemination of HCV in Scotland. Scottish sequences mainly formed discrete clusters interspersed between sequences from the rest of the world the most recent common ancestors of these clusters dated to 1942 to 1952 (Gt1a) and 1926 to 1942 (Gt3a), coincident with global ersification and distribution. Extant Scottish sequences originated in Edinburgh (Gt1a) and Glasgow (Gt3a) in the 1970s, but both genotypes spread from Glasgow to other regions. The dominant Gt1a strain differed between Edinburgh (cluster 2 [C2]), Glasgow (C3), and Aberdeen (C4), whereas significant Gt3a strain specificity occurred only in Aberdeen. Specific clusters initially formed separate transmission zones in Glasgow that subsequently overlapped, occasioning city-wide cocirculation. Transmission hot spots were detected with 45% of s les from patients residing in just 9 of Glasgow's 57 postcode districts. HCV was introduced into Scotland in the 1940s, concomitant with its worldwide dispersal likely arising from global-scale historical events. Cluster-specific transmission hubs were identified in Glasgow, the key Scottish city implicated in HCV dissemination. This fine-scale spatiotemporal reconstruction improves understanding of HCV transmission dynamics in Scotland. IMPORTANCE HCV is a major health burden and the leading cause of hepatocellular carcinoma. Public health needle exchange and “treatment as prevention” strategies targeting HCV are designed to reduce prevalence of the virus in people who inject drugs (PWID), potentially mitigating the future burden of HCV-associated liver disease. Understanding HCV transmission dynamics could increase the effectiveness of such public health initiatives by identifying and targeting regions playing a central role in virus dispersal. In this study, we examined HCV transmission in Scotland by analyzing the genetic relatedness of strains from PWID alongside data inferring the year in iduals became infected and residential information at a geographically finer-scale resolution than in previous studies. Clusters of Scotland-specific strains were identified with regional specificity, and mapping the spread of HCV allowed the identification of key areas central to HCV transmission in Scotland. This research provides a basis for identifying HCV transmission hot spots.
Publisher: Elsevier BV
Date: 2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-01-2014
DOI: 10.1002/HEP.26544
Publisher: Cold Spring Harbor Laboratory
Date: 14-11-2018
DOI: 10.1101/470633
Abstract: Advancing interventions to tackle the huge global burden of hepatitis B virus (HBV) infection depends on improved insights into virus epidemiology, transmission, within-host ersity, drug resistance and pathogenesis, all of which can be facilitated by the large-scale generation of full-length virus genome data. Here we describe advances to a protocol to exploit the circular HBV genome structure, using isothermal rolling-circle lification to enrich for HBV DNA and to generate concatemeric licons containing multiple successive copies of the same genome. We show that this product is suitable for Nanopore sequencing as single reads, as well as for generating short-read Illumina sequences. Nanopore reads can be used to implement a straightforward method for error correction that reduces the per-read error rate, by comparing multiple genome copies combined into a single concatemer and by comparing reads generated from plus and minus strands. Thus we can achieve improved consensus sequencing accuracy of 99.7% and resolve intra-s le sequence variants to form whole-genome haplotypes. The combination of isothermal lification and Nanopore sequencing offers the longer-term potential to develop point-of-care tests for HBV, which could also be adapted for other viruses.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Anna McNaughton.