Josh Singer

Josh Singer
University of Glasgow | UofG · MRC - University of Glasgow Centre for Virus Research

PhD

About

71
Publications
12,659
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1,443
Citations

Publications

Publications (71)
Article
Full-text available
Hepatitis C virus (HCV) is a highly diverse pathogen that frequently establishes a chronic long-term infection, but the origins and drivers of HCV diversity in the human population remain unclear. Previously unidentified strains of HCV genotype 6 (gt6) were recently discovered in chronically infected individuals of the Li ethnic group living in Bai...
Preprint
Full-text available
The availability of pathogen sequence data and use of genomic surveillance is rapidly increasing. Genomic tools and classification systems need updating to reflect this. Here, rabies virus is used as an example to showcase the potential value of updated genomic tools to enhance surveillance to better understand epidemiological dynamics and improve...
Article
Full-text available
Background: Rapid identification and investigation of healthcare-associated infections (HCAIs) is important for suppression of SARS-CoV-2, but the infection source for hospital onset COVID-19 infections (HOCIs) cannot always be readily identified based only on epidemiological data. Viral sequencing data provides additional information regarding pot...
Article
Full-text available
Virus host shifts are generally associated with novel adaptations to exploit the cells of the new host species optimally. Surprisingly, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has apparently required little to no significant adaptation to humans since the start of the Coronavirus Disease 2019 (COVID-19) pandemic and to October...
Article
Full-text available
Coronavirus disease 2019 (COVID-19) was first diagnosed in Scotland on 1 March 2020. During the first month of the outbreak, 2,641 cases of COVID-19 led to 1,832 hospital admissions, 207 intensive care admissions and 126 deaths. We aimed to identify the source and number of introductions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-...
Article
Full-text available
SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel virus of the family Coronaviridae. The virus causes the infectious disease COVID-19. The biology of coronaviruses has been studied for many years. However, bioinformatics tools designed explicitly for SARS-CoV-2 have only recently been developed as a rapid reaction to the need...
Article
Full-text available
Introduction Tenofovir disoproxil fumarate (TDF) is widely recommended for treatment of chronic hepatitis B virus (HBV) infection because it is safe, affordable and has a high genetic barrier to resistance. TDF resistance associated mutations (RAMs) have been reported, but data are limited, particularly for Africa. We set out to identify potential...
Preprint
Full-text available
CoV-GLUE is an online web application for the interpretation and analysis of SARS-CoV-2 virus genome sequences, with a focus on amino acid sequence variation. It is based on the GLUE data-centric bioinformatics environment and provides a browsable database of amino acid replacements and coding region indels that have been observed in sequences from...
Preprint
Full-text available
SARS-CoV-2, the causative agent of COVID-19, emerged in Wuhan, China in December 2019 and spread rapidly throughout the world. Understanding the introductions of this new coronavirus in different settings may assist control efforts and the establishment of frameworks to support rapid response in future infectious disease outbreaks. We investigated...
Preprint
Full-text available
RNA viruses are proficient at switching to novel host species due to their fast mutation rates. Implicit in this assumption is the need to evolve adaptations in the new host species to exploit their cells efficiently. However, SARS-CoV-2 has required no significant adaptation to humans since the pandemic began, with no observed selective sweeps to...
Preprint
Full-text available
SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel virus of the family Coronaviridae. The virus causes the infectious disease COVID-19. The biology of coronaviruses has been studied for many years. However, bioinformatics tools designed explicitly for SARS-CoV-2 have only recently been developed as a rapid reaction to the need...
Article
Full-text available
Genomic surveillance is an important aspect of contemporary disease management but has yet to be used routinely to monitor endemic disease transmission and control in low- and middle-income countries. Rabies is an almost invariably fatal viral disease that causes a large public health and economic burden in Asia and Africa, despite being entirely v...
Article
Full-text available
The mechanisms underlying virus emergence are rarely well understood, making the appearance of outbreaks largely unpredictable. Bluetongue virus serotype 8 (BTV-8), an arthropod-borne virus of ruminants, emerged in livestock in northern Europe in 2006, spreading to most European countries by 2009 and causing losses of billions of euros. Although th...
Preprint
Full-text available
Introduction: Tenofovir disoproxil fumarate (TDF) is widely recommended for treatment of chronic hepatitis B virus (HBV) infection because it is safe, affordable and has a high genetic barrier to resistance. TDF resistance associated mutations (RAMs) have been reported, but data are limited, particularly for Africa. We set out to identify RAMs in i...
Article
Full-text available
Genomic surveillance is an important aspect of contemporary disease management but has yet to be used routinely to monitor endemic disease transmission and control in low- and middle-income countries. Rabies is an almost invariably fatal viral disease that causes a large public health and economic burden in Asia and Africa, despite being entirely v...
Preprint
Full-text available
The mechanisms underlying virus emergence are rarely well understood, making the appearance of outbreaks largely unpredictable. Bluetongue virus serotype 8 (BTV-8), an insect-borne virus of ruminants, emerged in livestock in Northern Europe in 2006, spreading to most European countries by 2009 and causing losses of billions of Euros. Though the out...
Article
Full-text available
Persistent hepatitis E virus (HEV) infection is recognised in immunocompromised patients, particularly solid organ transplant (SOT) recipients. 1 The majority of cases are caused by genotype 3 (G3) HEV. 1 Ribavirin monotherapy is considered first-line when the reduction of immunosuppression is contraindicated or unsuccessful. 2 Treatment failure an...
Article
Full-text available
Using deep sequencing technologies such as Illumina’s platform, it is possible to obtain reads from the viral RNA population revealing the viral genome diversity within a single host. A range of software tools and pipelines can transform raw deep sequencing reads into Sequence Alignment Mapping (SAM) files. We propose that interpretation tools shou...
Article
Bluetongue virus (BTV) is an arbovirus transmitted by biting midges (Culicoides pp.). BTV causes a severe disease (bluetongue) in domestic and wild ruminant species with high levels of morbidity and mortality. Bluetongue has emerged as an important disease in sheep and cattle worldwide. The BTV genome is composed by ten linear dsRNA segments, packa...
Article
Full-text available
Background Virus genome sequences, generated in ever-higher volumes, can provide new scientific insights and inform our responses to epidemics and outbreaks. To facilitate interpretation, such data must be organised and processed within scalable computing resources that encapsulate virology expertise. GLUE (Genes Linked by Underlying Evolution) is...
Article
Full-text available
Background and rationale for the study: The global plan to eradicate hepatitis C (HCV) led by the World Health Organisation (WHO) outlines the use of highly effective direct-acting antiviral drugs (DAAs) to achieve elimination by 2030. Identifying individuals with active disease and investigation of the breadth of diversity of the virus sub-Sahara...
Article
Full-text available
Hepatitis C virus (HCV) is a global health issue. Although direct-acting antivirals are available to target HCV, there is currently no vaccine. The diversity of the virus is a major obstacle to HCV vaccine development. One approach toward a vaccine is to utilize a strategy to elicit broadly neutralizing antibodies (bNAbs) that target highly-conserv...
Article
Full-text available
A diverse range of DNA sequences derived from circoviruses (family Circoviridae) has been identified in samples obtained from humans and domestic animals, often in association with pathological conditions. In the majority of cases, however, little is known about the natural biology of the viruses from which these sequences are derived. Endogenous c...
Preprint
Full-text available
Small ruminant lentiviruses (SRLVs) cause chronic, persistent infections in populations of domestic sheep and goats throughout the world. In this study, we use genomic data to investigate the origins and history of the SRLV pandemic. To explore the hypothesis that SRLV infection disseminated during Neolithic times, we performed a serology and DNA s...
Preprint
Full-text available
A diverse range of DNA sequences derived from circoviruses (family Circoviridae) have been identified in samples obtained from humans and domestic animals, often in association with pathological conditions. In the majority of cases, however, little is known about the natural biology of the viruses from which these sequences are derived. Endogenous...
Preprint
Full-text available
Background: Virus genome sequences, generated in ever-higher volumes, can provide new scientific insights and inform our responses to epidemics and outbreaks. To facilitate interpretation, such data must be organised and processed within scalable computing resources that encapsulate virology expertise. GLUE (Genes Linked by Underlying Evolution) is...
Article
Full-text available
Circoviruses (family Circoviridae) are small, non-enveloped viruses that have short, single-stranded DNA genomes. Circovirus sequences are frequently recovered in metagenomic investigations, indicating that these viruses are widespread, yet they remain relatively poorly understood. Endogenous circoviral elements (CVe) are DNA sequences derived from...
Preprint
Full-text available
Circoviruses (family Circoviridae ) are small, non-enveloped viruses that have short, single-stranded DNA genomes. Circovirus sequences are frequently recovered in metagenomic investigations, indicating that these viruses are widespread, yet they remain relatively poorly understood. Endogenous circoviral elements (CVe) are DNA sequences derived fro...
Article
Full-text available
The host innate immune response mediated by type I interferon (IFN) and the resulting up-regulation of hundreds of interferon-stimulated genes (ISGs) provide an immediate barrier to virus infection. Studies of the type I ‘interferome’ have mainly been carried out at a single species level, often lacking the power necessary to understand key evoluti...
Data
ISG encoded transcript types. Barplots showing the types of transcripts generated by human genes significantly up-regulated (left panel) or down-regulated (right panel) in response to IFN. Transcript types were retrieved using BioMart from the Ensembl database. Some genes are annotated with > 1 transcript type; if one of the types was protein codin...
Data
Number of differentially expressed orthologous clusters/genes in response to type I IFN. (DOCX)
Data
Antiviral genes analysed in this study. (DOCX)
Data
R code used to generate Fig 4A. This R code requires Data S5 and Data S6 as input files, referred to in the code as Big_table_v3.6.1 and ASEPs, respectively. (TXT)
Data
Input file for R code used to generate Figures Fig 3B, Fig 4A and Fig 4B. This file, referred to as Big_table_v3.6.1 in the R code, contains data required to run the code present in S2 Data, S3 Data and S4 Data that is used to generated Fig 3B, Fig 4A and Fig 4B, respectively. (XLSX)
Data
Constitutive expression of ISGs in cells used in this study. Barplots showing the median basal FPKM levels for the whole interferome (left) or specific ISGs encoding known antiviral factors (right) for cells derived from each species analysed in this study in the absence of type I IFN treatment. Antiviral ISGs used in these graphs are provided in S...
Data
Core mammalian ISGs shown in Fig 5A. (DOCX)
Data
R code used to generate Fig 3B. This R code requires Data S5 as an input, referred to in the code as Big_table_v3.6.1. (TXT)
Data
R code used to generate Fig 4B. This R code requires Data S5 as an input, referred to in the code as Big_table_v3.6.1. (TXT)
Data
List of confirmed antiviral genes required as input for S2 Data. This file contains data required to run the code present in S2 Data that is used to generate Fig 3B. This file is referred to as ASEPs in the R code. (XLSX)
Data
A comparison of pig interferomes resulting from treatment with either UIFN or porcine IFNα. Interferomes were generated in primary pig fibroblasts using either porcine IFNα (n = 3) or UIFN (n = 3) (S1 Data). (A) A heatmap shows the log2FC values obtained for the corevert ISGs in response to either UIFN or porcine IFNα. A high level of concordance w...
Data
Reads generated for each dataset and mycoplasma screening. Mycoplasma can be detected in every deep sequencing experiment as either environmental or cell culture contaminants (S1 Data). Stacked barplots show the reads generated as part of this study where every bar represents a sample. Reads were assessed using FASTQC, trimmed, and mapped to the ap...
Data
Species and genome versions used for the DIGS analysis. (DOCX)
Data
The raw values relative to the figures displayed in this study. This file contains the data used to plot Figures displayed in the manuscript. R code and separate files used as inputs for the R code are present as additional files. (XLSX)
Data
Generation of transcriptomes used in this study. (A) Schematic outline of the experimental approach used to generate the interferomes used in this study. Parallel sets of cell cultures were used simultaneously. One set was used to determine the antiviral status of each cell line, while the other set was used to extract RNA and prepare libraries for...
Data
Origin of cells used in this study. (DOCX)
Article
Full-text available
The local search algorithm WSat is one of the most successful algorithms for solving the satisfiability (SAT) problem. It is notably effective at solving hard Random 3-SAT instances near the so-called `satisfiability threshold', but still shows a peak in search cost near the threshold and large variations in cost over different instances. We make a...
Article
Random-2+p-SAT interpolates between the polynomial-time problem Random-2-SAT when p = 0 and the NP-complete problem Random3 -SAT when p = 1. At some value p = p 0 0:41, a dramatic change in the structural nature of instances is predicted by statistical mechanics methods. This is reected by a change in the typical cost scaling for a complete search...
Article
The local search algorithm WSat is one of the most successful algorithms for solving the satisfiability (SAT) problem. It is notably effective at solving hard Random 3-SAT instances near the so-called `satisfiability threshold', but still shows a peak in search cost near the threshold and large variations in cost over different instances. We make a...
Conference Paper
This paper addresses an important but rarely discussed practical aspect of programming in a declarative language: its interface to other programming languages. We present the high-level, generic interface of ECLiPSe, and discuss the reasons for our design choices. The main feature of the interface is that it cleanly separates the code for ECLiPSe f...
Article
The local search algorithm WSat is one of the most successful algorithms for solving the archetypal NP-complete problem of satis ability (SAT). It is notably eective at solving Random-3-SAT instances near the so-called `satis ability threshold', which are thought to be universally hard. However, WSat still shows a peak in search cost near the thres...
Article
Full-text available
. Random 2+p-SAT interpolates between the polynomialtime problem Random 2-SAT when p = 0 and the NP-complete problem Random 3-SAT when p = 1. At some value p = p0 0:41, a dramatic change in the structural nature of instances is predicted by statistical mechanics methods. This is reflected by a change in the typical cost scaling for a complete searc...
Article
The local search algorithm Wsat is one of the most successful algorithms for solving the satisfiability (SAT) problem. It is notably effective at solving hard Random 3-SAT instances near the so-called `satisfiability threshold', but still shows a peak in search cost near the threshold and large variations in cost over different instances. We make a...

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