Biology subjects

Peacock, S. J.

Publications and source records attributed to Peacock, S. J..

13 recordsLinked to original sources

bioRxiv2026

Quantifying Exposure of Pacific Salmon and Steelhead to Climate Change in the Fraser River basin

Climate change can affect salmon and steelhead (Oncorhynchus spp.) throughout their anadromous life cycles, yet there have been no assessments of which Canadian populations face the greatest exposure. We developed a framework to quantify relative climate change exposure of salmon and steelhead populations based on the spatial and temporal distribution of different life stages. Exposure was calculated from climate model projections for freshwater and marine climate variables considering unique impact thresholds for each population and life stage. We applied this framework to 60 Conservation Units of Pacific salmon and steelhead in the Fraser River basin, British Columbia. Lake-type sockeye had the highest exposure, driven by elevated stream temperatures during adult freshwater migration and spawning stages and relatively low thermal tolerance of marine stages. Chinook salmon were the next most exposed, while coho, pink, and chum salmon had relatively low exposure. Uniquely, steelhead exposure was driven by high stream temperatures during incubation. Our framework is broadly applicable, and our findings provide critical input for climate change vulnerability assessments and forward-looking resilience planning for Pacific salmon.

ecology↗

bioRxiv2025

BaGPipe: an automated, reproducible, and flexible pipeline for bacterial genome-wide association studies

Microbial genome-wide association study (GWAS) tools often require manual data processing steps, lack comprehensive workflows, and are limited by scalability issues, thus hindering the exploration of bacterial genetic traits. To address these challenges, we developed BaGPipe, an automated and flexible bacterial GWAS pipeline built using Nextflow and incorporating Pyseer for association analysis. BaGPipe integrates all essential components of a bacterial GWAS--spanning pre-processing, statistical analysis, and downstream visualisation--into a unified workflow that is reproducible and easy to deploy across diverse computational environments. BaGPipe was validated on a publicly available dataset of Streptococcus pneumoniae whole-genome sequences, and reproduced published findings with improved computational efficiency. BaGPipe was then applied to a dataset of Staphylococcus aureus whole-genome sequences, successfully identifying known and novel antibiotic resistance associations. By offering an accessible, efficient, and reproducible platform, BaGPipe accelerates bacterial GWAS and facilitates deeper exploration into the genetic underpinnings of phenotypic traits. Impact StatementThe increasing availability of bacterial genome sequences has created an opportunity for robust, reproducible tools to facilitate the discovery of novel genotype-phenotype associations. Despite the demonstrated utility of genome-wide association studies (GWAS) in identifying genetic determinants of disease, toxicity and antibiotic resistance, existing tools for bacterial GWAS often involve fragmented workflows requiring extensive manual intervention, limiting their adoption and reproducibility. Here, we introduce BaGPipe, a fully integrated bacterial GWAS pipeline that automates pre-processing, statistical analysis, and visualisation, thereby streamlining the entire workflow. With its flexibility, scalability, and ease of use, BaGPipe makes bacterial GWAS more accessible to researchers, enabling faster and more reliable insights into microbial genetics. This is an important step towards overcoming the computational and logistical barriers that have constrained bacterial GWAS, ultimately accelerating research into microbial evolution, resistance mechanisms, and the genetic basis of other key phenotypic traits. Data SummaryBaGPipe is freely available at https://github.com/sanger-pathogens/BaGPipe. The Streptococcus pneumoniae input dataset is available from the Pyseer tutorial (https://pyseer.readthedocs.io/en/master/tutorial.html#). The Staphylococcus aureus sequencing assemblies can be sourced from their ERS accession numbers provided in supplementary data. The reference assemblies, listed in the supplementary, can be sourced from NCBI.

bioinformatics↗

bioRxiv2024

Monitoring for fisheries or for fish? Declines in monitoring of salmon spawners continue despite a conservation crisis

Monitoring of salmon in Pacific Canada has been declining for decades. Counts of spawning salmon are critically important, enabling researchers to quantify impacts of stressors, identify when and where management interventions are required to avoid extirpations, and evaluate the efficacy of recovery efforts. These data are more important now than ever, as uniquely adapted spawning populations underlie salmon resilience and their ability to adapt to climate change, and fine-scale data can inform sustainable fishing opportunities including the revitalization of terminal fisheries. We revisit the state of Pacific salmon spawner data from the Yukon to southern British Columbia. Almost two-thirds of salmon populations that were historically monitored have no reported estimates in 2014-2023 - the worst decade for data since broadscale spawner surveys began in the 1950s. We found a positive association between the number of populations monitored and landed value for three of the five Pacific salmon species, suggesting that monitoring is, to some extent, motivated by the information needs of commercial fisheries management. We recommend aligning monitoring objectives and strategic investments to improve monitoring outcomes for salmon, ecosystems, and the communities that depend on them. We emphasize data stewardship, as ensuring access to these baseline data is a cornerstone for rebuilding wild Pacific salmon.

ecology↗

bioRxiv2023

The mutational landscape of Staphylococcus aureus during colonisation

Staphylococcus aureus is an important human pathogen but is primarily a commensal of the human nose and skin. Survival during colonisation is likely one of the major drivers of S. aureus evolution. Here we use a genome-wide mutation enrichment approach to analyse a genomic dataset of 3,060 S. aureus isolates from 791 individuals to show that despite limited within-host genetic diversity, an excess of protein-altering mutations can be found in genes encoding key metabolic pathways, in regulators of quorum-sensing and in known antibiotic targets. Nitrogen metabolism and riboflavin synthesis are the metabolic processes with strongest evidence of adaptation. Further evidence of adaptation to nitrogen availability was revealed by enrichment of mutations in the assimilatory nitrite reductase and urease, including mutations that enhance growth with urea as the sole nitrogen source. Inclusion of an additional 4,090 genomes from 802 individuals revealed eight additional genes including sasA/sraP, pstA, and rsbU with signals adaptive variation that warrant further characterisation. Our study provides the most comprehensive picture to date of the heterogeneity of adaptive changes that occur in the genomes of S. aureus during colonisation, revealing the likely importance of nitrogen metabolism, loss of quorum sensing and antibiotic resistance for successful human colonisation.

genomics↗

bioRxiv2022

Exploring the mobilome and resistome of Enterococcus faecium in a One Health context across two continents

Enterococcus faecium is a ubiquitous opportunistic pathogen that is exhibiting increasing levels of antimicrobial resistance (AMR). Many of the genes that confer resistance and pathogenic functions are localized on mobile genetic elements (MGEs), which facilitate their transfer between lineages. Here, features including resistance determinants, virulence factors, and MGEs were profiled in a set of 1273 E. faecium genomes from two disparate geographic locations (in the UK and Canada) from a range of agricultural, clinical, and associated habitats. Neither lineages of E. faecium nor MGEs are constrained by geographic proximity, but our results show evidence of a strong association of many profiled genes and MGEs with habitat. Many features were associated with a group of clinical and municipal wastewater genomes that are likely forming a new human-associated ecotype. The evolutionary dynamics of E. faecium make it a highly versatile emerging pathogen, and its ability to acquire, transmit, and lose features presents a high risk for the emergence of new pathogenic variants and novel resistance combinations. This study provides a workflow for MGE-centric surveillance of AMR in Enterococcus that can be adapted to other pathogens.

genomics↗

bioRxiv2020

MAJORA: Continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance

Genomic epidemiology has become an increasingly common tool for epidemic response. Recent technological advances have made it possible to sequence genomes rapidly enough to inform outbreak response, and cheaply enough to justify dense sampling of even large epidemics. With increased availability of sequencing it is possible for agile networks of sequencing facilities to collaborate on the sequencing and analysis of epidemic genomic data. In response to the ongoing SARS-CoV-2 pandemic in the United Kingdom, the COVID-19 Genomics UK (COG-UK) consortium was formed with the aim of rapidly sequencing SARS-CoV-2 genomes as part of a national-scale genomic surveillance strategy. The network consists of universities, academic institutes, regional sequencing centres and the four UK Public Health Agencies. We describe the development and deployment of Majora, an encompassing digital infrastructure to address the challenge of collecting and integrating both genomic sequencing data and sample-associated metadata produced across the COG-UK network. The system was designed and implemented pragmatically to stand up capacity rapidly in a pandemic caused by a novel virus. This approach has underpinned the success of COG-UK, which has rapidly become the leading contributor of SARS-CoV-2 genomes to international databases and has generated over 60,000 sequences to date.

bioinformatics↗

bioRxiv2020

Co-evolutionary signals from Burkholderia pseudomallei population genomics highlight its survival strategy in a hostile environment

BackgroundThe soil bacterium Burkholderia pseudomallei is the causative agent of melioidosis. It kills up to 40% of cases and contributes to human morbidity and mortality in many tropical and sub-tropical countries. As no vaccines are currently available, prevention is the key health policy and is achieved by avoiding direct contact with soil and standing water. The pathogen notoriously persists in ranges of environmental conditions which make disease prevention difficult. We aimed to scan B. pseudomallei genomes for signals of evolutionary adaptations that allow it to thrive across environmental conditions, which should ultimately inform prevention policy. MethodsWe conducted three layers of analyses: a genome-wide epistasis and co-selection study (GWES) on 2,011 B. pseudomallei genomes to detect signals of co-selection; gene expression analyses across 82 diverse physical, chemical, biological and infectious conditions to identify specific conditions in which such selection might have acted; and gene knockout assays to confirm the function of the co-selection hotspot. FindingsWe uncovered 13,061 mutation pairs in distinct genes and non-coding RNA that have been repeatedly co-selected through B. pseudomallei evolution. Genes under co-selection displayed marked expression correlation when B. pseudomallei was subjected to physical stress conditions including temperature stress, osmotic stress, UV radiation, and nutrient deprivation; highlighting these conditions as the major evolutionary driving forces for this bacterium. We identified a putative adhesin (BPSL1661) as a hub of co-selection signals, experimentally confirmed the role of BPSL1661 under nutrient deprivation, and explored the functional basis of the co-selection gene network surrounding BPSL1661 in facilitating bacterial survival under nutrient depletion. InterpretationOur findings suggest that B. pseudomallei has a selective advantage to survive nutrient-limited conditions. Anthropogenic activities such as shifting cultivation systems with more frequent rotations of cropping and shortened fallow periods or continuous cultivation of cash crops could directly or indirectly contribute to loss of soil nutrient; these may lead to the preferential survival of B. pseudomallei and a subsequent rise of melioidosis. Successful disease control for melioidosis needs to consider improving environmental health in addition to current preventive efforts. FundingWellcome Trust, European Research Council, UK Department of Health, Thailand Research Fund and Khon Kaen University Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed with terms (co-selection AND bacteria AND population) with no date or language restrictions from database inception until April 11, 2021. We identified 44 publications of which four were conducted at a genome-wide scale. These four studies were performed on human-restricted pathogens, detected co-selection of antibiotic resistance gene networks which highlight the use of antibiotics as major selection pressures and further inform treatment options. However, none of these studies were performed on Burkholderia pseudomallei or other opportunistic pathogens that have been adapted to both natural and host environments. The selection pressures exerted on these pathogens and the genetic determinants allowed for their adaptations remain unclear, which limit our understanding on the bacterial biology and the information used for disease control. Added value of this studyBased on genomes of 2,011 B. pseudomallei collected from melioidosis endemic areas, we identified and confirmed genetic signals for co-selection. Using transcriptome profiling covering a broad spectrum of conditions and exposures, we showed that genes under co-selection displayed marked expression correlation under physical stress conditions with the gene at the co-selection hotspot conditionally expressed under nutrient starvation. Furthermore, we experimentally validated the function of the hotspot gene and demonstrated that unlike host-restricted pathogens, the B. pseudomallei co-selection network does not facilitate host infection but is focused on bacterial survival in a harsh environment, particularly under nutrient depletion. Aside from providing a data resource, the study also showcases the power of combined genetics, transcriptomics and functional analysis as a tool for biology discovery. Implications of all available evidenceOur findings provide evolutionary and biological evidence for preferential survival of B. pseudomallei under nutrient starvation. Agricultural practice that induces soil loss, which is not uncommon in melioidosis endemic areas has been linked to soil nutrient depletion and may contribute to the prevalence of B. pseudomallei and a consequent rise of melioidosis in these regions. Successful melioidosis control has to consider environmental health in addition to existing prevention policy.

microbiology↗

bioRxiv2019

Evaluating the consequences of common assumptions in run reconstructions on Pacific-salmon biological status assessments

Information on biological status is essential for designing, implementing, and evaluating management strategies and recovery plans for threatened or exploited species. However, the data required to quantify status are often limited, and it is important to understand how assessments of status may be biased by assumptions in data analysis. For Pacific salmon, biological status assessments based on spawner abundances and spawner-recruitment (SR) analyses often involve "run reconstructions" that impute missing spawner data, expand observed spawner abundance to account for unmonitored streams, assign catch to individual stocks, and quantify age-at-return. Using a stochastic simulation approach, we quantified how common assumptions in run reconstructions biased assessments of biological status based on spawner abundance. We found that status assessments were robust to most common assumptions in run reconstructions, even in the face of declining monitoring coverage, but that overestimating catch tended to increase rates of status misclassification. Our results lend confidence to biological status assessments based on spawner abundances and SR analyses, even in the face of incomplete data.

ecology↗

bioRxiv2019

Contrasting approaches to genome-wide association studies impact the detection of resistance mechanisms in Staphylococcus aureus

Rapid detection of antibiotic resistance using whole-genome sequencing (WGS) could improve clinical outcomes and limit the spread of resistance. For this to succeed, we need an accurate way of linking genotype to phenotype, that identifies new resistance mechanisms as they appear. To assess how close we are to this goal, we characterized antimicrobial resistance determinants in >4,000 Staphylococcus aureus genomes of isolates associated with bloodstream infection in the United Kingdom and Ireland. We sought to answer three questions: 1) how well did known resistance mechanisms explain phenotypic resistance in our collection, 2) how many previously identified resistance mechanisms appeared in our collection, and 3) how many of these were detectable using four contrasting genome-wide association study (GWAS) methods. Resistance prediction based on the detection of known resistance determinants was 98.8% accurate. We identified challenges in correcting for population structure, clustering orthologous genes, and identifying causal mechanisms in rare or common phenotypes, which reduced the recovery of known mechanisms. Limited sensitivity and specificity of these methods made prediction using GWAS-discovered hits alone less accurate than using literature-derived genetic determinants. However, GWAS methods identified novel mutations associated with resistance, including five mutations in rpsJ, which improved tetracycline resistance prediction for 28 isolates, and a T118I substitution in fusA which resulted in better fusidic acid resistance prediction for 5 isolates. Thus, GWAS approaches in conjunction with phenotypic testing data can support the development of comprehensive databases to enable real-time use of WGS for patient management.

bioinformatics↗

bioRxiv2019

The emergence of successful Streptococcus pyogenes lineages through convergent pathways of capsule loss and recombination directing high toxin expression

Gene transfer and homologous recombination in Streptococcus pyogenes has the potential to trigger the emergence of pandemic lineages, as exemplified by lineages of emm1 and emm89 that emerged in the 1980s and 2000s respectively. Although near-identical replacement gene transfer events in the nga (NADase) and slo (Streptolysin O) locus conferring high expression of these toxins underpinned the success of these lineages, extension to other emm-genotype lineages is unreported. The emergent emm89 lineage was characterised by five regions of homologous recombination additional to nga/slo, including complete loss of the hyaluronic acid capsule synthesis locus hasABC, a genetic trait replicated in two other leading emm types and recapitulated by other emm types by inactivating mutations. We hypothesised that other leading genotypes may have undergone a similar recombination events. We analysed a longitudinal dataset of genomes from 344 clinical invasive disease isolates representative of locations across England, dating from 2001 to 2011, and an international collection of S. pyogenes genomes representing 54 different genotypes, and found frequent evidence of recombination events at the nga-slo locus predicted to confer higher toxin expression. We identified multiple associations between recombination at this locus and inactivating mutations within hasA/B, suggesting convergent evolutionary pathways in successful genotypes. This included common genotypes emm28 and emm87. The combination of no or low capsule, and high expression of nga and slo, may underpin the success for many emergent S. pyogenes lineages of different genotypes, triggering new pandemics and could change the way S. pyogenes causes disease.\n\nImportanceStreptococcus pyogenes is a genetically diverse pathogen, with over 200 different genotypes defined by emm typing, but only a minority of these genotypes are responsible for majority of human infection in high income countries. Two prevalent genotypes associated with disease rose to international dominance following recombination of a toxin locus that conferred increased expression. Here, we found that recombination of this locus and promoter has occurred in other diverse genotypes, events that may allow these genotypes to expand in the population. We identified an association between the loss of hyaluronic acid capsule synthesis and high toxin expression, which we propose may be associated with an adaptive advantage. As S. pyogenes pathogenesis depends both on capsule and toxin production, new variants with altered expression may result in abrupt changes in the molecular epidemiology of this pathogen in the human population over time.

microbiology↗

bioRxiv2018

One Health genomic surveillance of Escherichia coli demonstrates distinct lineages and mobile genetic elements in isolates from humans versus livestock

Livestock have been proposed as a reservoir for drug-resistant Escherichia coli that infect humans. We isolated and sequenced 431 E. coli (including 155 ESBL-producing isolates) from cross-sectional surveys of livestock farms and retail meat in the East of England. These were compared with the genomes of 1517 E. coli associated with bloodstream infection in the United Kingdom. Phylogenetic core genome comparisons demonstrated that livestock and patient isolates were genetically distinct, indicating that E. coli causing serious human infection do not directly originate from livestock. By contrast, we observed highly related isolates from the same animal species on different farms. Analysis of accessory (variable) genomes identified a virulence cassette associated previously with cystitis and neonatal meningitis that was only present in isolates from humans. Screening all 1948 isolates for accessory genes encoding antibiotic resistance revealed 41 different genes present in variable proportions of humans and livestock isolates. We identified a low prevalence of shared antimicrobial resistance genes between livestock and humans based on analysis of mobile genetic elements and long-read sequencing. We conclude that in this setting, there was limited evidence to support the suggestion that antimicrobial resistant pathogens that cause serious infection in humans originate from livestock.\n\nImportanceThe increasing prevalence of E. coli bloodstream infections is a serious public health problem. We used genomic epidemiology in a One Health study conducted in the East of England to examine putative sources of E. coli associated with serious human disease. E. coli from 1517 patients with bloodstream infection were compared with 431 isolates from livestock farms and meat. Livestock-associated and bloodstream isolates were genetically distinct populations based on core genome and accessory genome analyses. Identical antimicrobial resistance genes were found in livestock and human isolates, but there was little overlap in the mobile elements carrying these genes. In addition, a virulence cassette found in humans isolates was not identified in any livestock-associated isolate. Our findings do not support the idea that E. coli causing invasive disease or their resistance genes are commonly acquired from livestock.

genomics↗

bioRxiv2017

Global phylogenomics of multidrug-resistant Staphylococcus aureus sequence type 772: the Bengal Bay clone

The global spread of antimicrobial resistance has been well documented in Gram-negative bacteria and healthcare-associated epidemic pathogens, often emerging from regions with heavy antimicrobial use. However, the degree to which similar processes occur with Gram-positive bacteria in the community setting is less well understood. Here we demonstrate the recent origin and global spread from the Indian subcontinent of a multidrug resistant Staphylococcus aureus lineage, sequence type 772 (Bengal Bay clone). Short-term outbreaks occurred following intercontinental transmission, typically associated with travel and family contacts, but ongoing endemic transmission was uncommon. Instrumental in the emergence of a single dominant clade in the early 1990s was the acquisition of a multidrug resistance integrated plasmid that did not appear to incur a significant fitness cost. The Bengal Bay clone therefore combines the multidrug resistance of traditional healthcare-associated clones with the epidemiological and virulence potential of community-associated clones.

genomics↗

bioRxiv2016

Signatures of non-neutral processes within the population structure of Streptococcus pneumoniae

Populations of Streptococcus pneumoniae (SP) are typically structured into groups of closely related organisms or lineages, but it is not clear whether they are maintained by selection or neutral processes. Here, we attempt to address this question by applying a machine learning technique to SP whole genomes. Our results indicate that lineages evolved through immune selection on the groEL chaperone protein. The groEL protein is part of the groESL operon and enables a large range of proteins to fold correctly within the physical environment of the nasopharynx, thereby explaining why lineage structure is so stable within SP despite high levels of genetic transfer. SP is also antigenically diverse, exhibiting a variety of distinct capsular serotypes. Associations exist between lineage and capsular serotype but these can be easily perturbed, such as by vaccination. Overall, our analyses indicate that the evolution of SP can be conceptualized as the rearrangement of modular functional units occurring on several different timescales under different pressures: some patterns have locked in early (such as the epistatic interactions between groESL and a constellation of other genes) and preserve the differentiation of lineages, while others (such as the associations between capsular serotype and lineage) remain in continuous flux.

epidemiology↗