Biology subjects

Tagg, K. A.

Publications and source records attributed to Tagg, K. A..

6 recordsLinked to original sources

bioRxiv2025

Jaccard Index Network Analysis for pangenome analysis

ii.Summary/AbstractJaccard Index Network Analysis (JINA) is a comprehensive workflow designed to explore bacterial genome relationships through an integrated network-based approach. This workflow combines existing tools such as Jaccard Index (1), Gephi (2) and Pangraph (3). By integrating these methodologies into a unified framework, JINA enables efficient visualization and stratification of genomic data, facilitating the identification of meaningful patterns, groups, and associations within bacterial populations. The use of JINA ensures precision in capturing genomic variation including single nucleotide polymorphisms, insertions and deletions. While JINA does not implement Gephi, BLAST, and PanGraph directly in a single software, it guides their coordinated use to analyze and interpret genomic data effectively.

bioinformatics↗

bioRxiv2024

Typhi Mykrobe: fast and accurate lineage identification and antimicrobial resistance genotyping directly from sequence reads for the typhoid fever agent Salmonella Typhi

BackgroundTyphoid fever results from systemic infection with Salmonella enterica serovar Typhi (Typhi) and causes 10 million illnesses annually. Disease control relies on prevention (water, sanitation, and hygiene interventions or vaccination) and effective antimicrobial treatment. Antimicrobial resistant (AMR) Typhi lineages have emerged and become established in many parts of the world. Knowledge of local pathogen populations informed by genomic surveillance, including of lineages (defined by the GenoTyphi scheme) and AMR determinants, is increasingly used to inform local treatment guidelines and to inform vaccination strategy. Current tools for genotyping Typhi require multiple read alignment or assembly steps and have not been validated for analysis of data generated with Oxford Nanopore Technologies (ONT) long-read sequencing devices. Here, we introduce Typhi Mykrobe, a command line software tool for rapid genotyping of Typhi lineages, AMR determinants, and plasmid replicons direct from sequencing reads. ResultsWe validated Typhi Mykrobe lineage genotyping by comparison with the current standard read mapping-based approach and demonstrated 99.8% concordance across nearly 13,000 genomes sequenced with Illumina platforms. For the few isolates with discordant calls, we show that Typhi Mykrobe results are better supported by the evidence from raw sequence read data than the results generated using the mapping-based approach. We also demonstrate 99.9% concordance for detection of AMR determinants compared with the current standard assembly-based approach, with similar results for plasmid marker detection. Typhi Mykrobe predicts clinical resistance categorisation (S/I/R) for eight drug classes, and we show strong agreement with phenotypic categorisations generated from reference laboratory minimum inhibitory concentration (MIC) data for n=1,572 Illumina-sequenced isolates (>99% agreement within one doubling dilution). We show strong concordance (>96% for genotype and >98% for AMR and plasmid) between calls made from ONT reads and those made from Illumina reads for isolates sequenced on both platforms (n =93 genomes). Typhi Mykrobe takes less than a minute per sample and is available at https://github.com/typhoidgenomics/genotyphi. ConclusionsTyphi Mykrobe provides rapid and sensitive genotyping of Typhi genomes direct from Illumina and ONT reads, although lower accuracy was observed for R9 ONT data. It demonstrated accurate assignment of GenoTyphi lineage, detection of AMR determinants and prediction of corresponding AMR phenotypes, and identification of plasmid replicons.

microbiology↗

bioRxiv2023

Harnessing the pangenome for genomic surveillance: Salmonella enterica serotype Typhi as a paradigm

Public health genomic surveillance systems typically measure genome relatedness and infer molecular epidemiological relationships using chromosomal loci alone - an approximation of vertical evolution, or homology-by-descent. The accessory genome, composed of plasmids and other mobile genetic elements, reflects horizontal gene transfer and serves as an important mechanism of bacterial evolution, enabling rapid adaptation. Measuring homology in the accessory genome - homology-by-admixture - could offer important molecular epidemiological information for public health application. We applied Jaccard Index and a novel genome length distance metric to compute pangenome relatedness for the globally-important pathogen Salmonella enterica serotype Typhi (Typhi), and graphically express both homology-by-descent and homology-by-admixture in a reticulate network. Jaccard Index Network Analysis revealed structure in the Typhi pangenome that can be harnessed to enhance discriminatory power for surveillance, track antimicrobial resistance, and refine our understanding of homology for outbreak management and prevention. This offers a more intricate, multidimensional framework for understanding pathogen evolution. Significance StatementBacterial relatedness is often measured and visualized using chromosomal comparison and phylogenetic trees. While valuable, this approach captures only the vertical evolutionary dimension and excludes genetic material acquired or lost through horizontal gene transfer. We present an approach for measuring and visualizing bacterial relatedness using all core and accessory genetic material and discuss the interpretation of resulting reticulate networks of bacterial genomes. In application to Salmonella Typhi, Jaccard Index Network Analysis revealed structure in populations of this pathogen that may be harnessed for public health applications. This approach captures both vertical and horizontal evolutionary dimensions, offering an intricate genetic framework for exploring pathogen evolution.

genomics↗

bioRxiv2020

COPLA, a taxonomic classifier of plasmids

The Plasmid Taxonomic Unit (PTU) concept is an initial step for a natural classification of plasmids. Here we present COPLA, a software for plasmid assignation to existing PTUs. To assess its performance, we used a sample of 1,000 plasmids missing from its current database. Overall, 41% of samples could be assigned an existing PTU (63% within the most abundant order, Enterobacterales), while 4% of samples could help to define new PTUs once COPLA database was updated.

bioinformatics↗

bioRxiv2019

Emergence of a novel Salmonella enterica serotype Reading clone is linked to its expansion in commercial turkey production, resulting in unanticipated human illness in North America

Concurrent separate human outbreaks of Salmonella enterica serotype Reading occurred in 2017-2019 in the United States and Canada, which were both linked to the consumption of raw turkey products. In this study, a comprehensive genomic investigation was conducted to reconstruct the evolutionary history of S. Reading from turkeys, and to determine the genomic context of outbreaks involving this rarely isolated Salmonella serotype. A total of 988 isolates of U.S. origin were examined using whole genome-based approaches, including current and historical isolates from humans, meat, and live food animals. Broadly, isolates clustered into three major clades, with one apparently highly adapted turkey clade. Within the turkey clade isolates clustered into three subclades, including an "emergent" clade that only contained isolates dated 2016 or later, including many of the isolates from these outbreaks. Genomic differences were identified between emergent and other turkey subclades suggesting that the apparent success of currently circulating subclades clade is, in part, attributable to plasmid acquisitions conferring antimicrobial resistance, gain of phage-like sequences with cargo virulence factors, and mutations in systems that may be involved in beta-glucuronidase activity and resistance towards colicins. U.S. and Canadian outbreak isolates were found interspersed throughout the emergent subclade and the other circulating subclade. The emergence of a novel S. Reading turkey subclade, coinciding temporally with expansion in commercial turkey production and with U.S. and Canadian human outbreaks, indicates that emergent strains with higher potential for niche success were likely vertically transferred and rapidly disseminated from a common source. ImportanceIncreasingly, outbreak investigations involving foodborne pathogens are confounded by the inter-connectedness of food animal production and distribution, necessitating high-resolution genomic investigations to determine their basis. Fortunately, surveillance and whole genome sequencing, combined with the public availability of these data, enable comprehensive queries to determine underlying causes of such outbreaks. Utilizing this pipeline, it was determined that a novel clone of Salmonella Reading has emerged that coincides with increased abundance in raw turkey products and two outbreaks of human illness in North America. The rapid dissemination of this highly adapted and conserved clone indicates that it was likely obtained from a common source and rapidly disseminated across turkey production. Key genomic changes may have contributed to its apparent continued success in the barn environment, and ability to cause illness in humans.

microbiology↗

bioRxiv2019

Novel quinolone resistance determinant, qepA8, in Shigella flexneri isolated in the United States, 2016

A qepA8+ Shigella flexneri was cultured from the stool of a traveler returning from India and East Asia. This chromosomally encoded qepA variant, has a six-base insertion, and may have been mobilized as part of a complex IS1-mediated composite transposon including catA1, aadA1, and blaOXA-1. In laboratory E. coli, qepA8 alone only conferred decreased ciprofloxacin susceptibility; however, it may work in combination with additional mechanisms to confer clinical resistance.

microbiology↗