ORCID Profile
0000-0003-0739-6848
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Publisher: Microbiology Society
Date: 29-04-2016
Publisher: Microbiology Society
Date: 13-06-2017
Publisher: Oxford University Press (OUP)
Date: 21-01-2016
DOI: 10.1093/BIOINFORMATICS/BTW022
Abstract: Summary: Transposon insertion sequencing is a high-throughput technique for assaying large libraries of otherwise isogenic transposon mutants providing insight into gene essentiality, gene function and genetic interactions. We previously developed the Transposon Directed Insertion Sequencing (TraDIS) protocol for this purpose, which utilizes shearing of genomic DNA followed by specific PCR lification of transposon-containing fragments and Illumina sequencing. Here we describe an optimized high-yield library preparation and sequencing protocol for TraDIS experiments and a novel software pipeline for analysis of the resulting data. The Bio-Tradis analysis pipeline is implemented as an extensible Perl library which can either be used as is, or as a basis for the development of more advanced analysis tools. This article can serve as a general reference for the application of the TraDIS methodology. Availability and implementation: The optimized sequencing protocol is included as supplementary information. The Bio-Tradis analysis pipeline is available under a GPL license at anger-pathogens/Bio-Tradis Contact: parkhill@sanger.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.
Publisher: Cold Spring Harbor Laboratory
Date: 03-07-2020
DOI: 10.1101/2020.07.03.186692
Abstract: Microbial whole-genome sequencing (WGS) is now increasingly used to inform public health investigations of infectious disease. This approach has transformed our understanding of the global population structure of Salmonella enterica serovar Typhi ( S. Typhi), the causative agent of typhoid fever. WGS has been particularly informative for understanding the global spread of multi-drug resistant (MDR) typhoid. As WGS capacity becomes more decentralised, there is a growing opportunity for collaboration and sharing of surveillance data within and between countries to inform disease control policies. This requires freely available, community driven tools that reduce the barriers to access genomic data for public health surveillance and that deliver genomic data on a global scale. Here we present the Pathogenwatch ( pathogen.watch/styphi ) scheme for S. Typhi, a web application enabling the rapid identification of genomic markers of antimicrobial resistance (AMR) and contextualization with public genomic data to identify high-risk clones at a population level. Data are delivered in single genome reports or in collections of genomes combined with geographic and other data using trees, maps and tables. We show that the clustering of S. Typhi genomes in Pathogenwatch is comparable to established bioinformatics methods, and that genomic predictions of AMR are largely concordant with phenotypic drug susceptibility data. We demonstrate the public health utility of Pathogenwatch with ex les selected from over 4,300 public genomes available in the application. Pathogenwatch democratises genomic epidemiology of S. Typhi by providing an intuitive entry point for the analysis of WGS and linked epidemiological data, enabling international public health monitoring of the emergence and spread of high risk clones.
Publisher: Springer Science and Business Media LLC
Date: 30-11-2018
DOI: 10.1038/S41467-018-07370-Z
Abstract: There is paucity of data regarding the geographical distribution, incidence, and phylogenetics of multi-drug resistant (MDR) Salmonella Typhi in sub-Saharan Africa. Here we present a phylogenetic reconstruction of whole genome sequenced 249 contemporaneous S . Typhi isolated between 2008-2015 in 11 sub-Saharan African countries, in context of the 2,057 global S . Typhi genomic framework. Despite the broad genetic ersity, the majority of organisms (225/249 90%) belong to only three genotypes, 4.3.1 (H58) (99/249 40%), 3.1.1 (97/249 39%), and 2.3.2 (29/249 12%). Genotypes 4.3.1 and 3.1.1 are confined within East and West Africa, respectively. MDR phenotype is found in over 50% of organisms restricted within these dominant genotypes. High incidences of MDR S . Typhi are calculated in locations with a high burden of typhoid, specifically in children aged years. Antimicrobial stewardship, MDR surveillance, and the introduction of typhoid conjugate vaccines will be critical for the control of MDR typhoid in Africa.
Publisher: Oxford University Press (OUP)
Date: 23-11-2011
DOI: 10.1093/NAR/GKR1032
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 11-2017
Publisher: Cold Spring Harbor Laboratory
Date: 30-12-2022
DOI: 10.1101/2022.12.28.22283969
Abstract: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks twenty-one years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000), and provides a detailed overview of global genotype and antimicrobial resistance (AMR) distribution and temporal trends, generated using open analysis platforms (GenoTyphi and Pathogenwatch). Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show potential of travel-associated data to provide informal “sentinel” surveillance for such locations. The data indicate ciprofloxacin non-susceptibility ( resistance determinant) is widespread across geographies and genotypes, with high-level resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020), but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. The Consortium’s aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Jacqueline A. Keane.