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Ensemble of deep learning language models to support the creation of living systematic reviews for the COVID-19 literature: a retrospective study

BackgroundThe COVID-19 pandemic has led to an unprecedented amount of scientific publications, growing at a pace never seen before. Multiple living systematic reviews have been developed to assist professionals with up-to-date and trustworthy health information, but it is increasingly challenging for systematic reviewers to keep up with the evidence in electronic databases. We aimed to investigate deep learning-based machine learning algorithms to classify COVID-19 related publications to help scale-up the epidemiological curation process. MethodsIn this retrospective study, five different pre-trained deep learning-based language models were fine-tuned on a dataset of 6,365 publications manually classified into two classes, three subclasses and 22 sub-subclasses relevant for epidemiological triage purposes. In a k-fold cross-validation setting, each standalone model was assessed on a classification task and compared against an ensemble, which takes the standalone model predictions as input and uses different strategies to infer the optimal article class. A ranking task was also considered, in which the model outputs a ranked list of sub-subclasses associated with the article. ResultsThe ensemble model significantly outperformed the standalone classifiers, achieving a F1-score of 89.2 at the class level of the classification task. The difference between the standalone and ensemble models increases at the sub-subclass level, where the ensemble reaches a micro F1-score of 70% against 67% for the best performing standalone model. For the ranking task, the ensemble obtained the highest recall@3, with a performance of 89%. Using an unanimity voting rule, the ensemble can provide predictions with higher confidence on a subset of the data, achieving detection of original papers with a F1-score up to 97% on a subset of 80% of the collection instead of 93% on the whole dataset. ConclusionThis study shows the potential of using deep learning language models to perform triage of COVID-19 references efficiently and support epidemiological curation and review. The ensemble consistently and significantly outperforms any standalone model. Fine-tuning the voting strategy thresholds is an interesting alternative to annotate a subset with higher predictive confidence.

bioinformatics↗

Pyricularia Populations are Mostly Host-Specialized with Limited Reciprocal Cross-Infection Between Wheat and Endemic Grasses in Minas Gerais, Brazil

Wheat blast, caused by Pyricularia oryzae Triticum (PoT), is an emergent threat to wheat production. Current understanding of the evolution and population biology of the pathogen and epidemiology of the disease has been based on phylogenomic studies that compared the wheat blast pathogen with isolates collected from grasses that were invasive to Brazilian wheat fields. Genetic similarity between isolates from wheat and grasses lead to the conclusion that significant cross-infection occurs, especially on signalgrass (Urochloa spp.); and this in turn prompted speculation that its widespread use as forage is a key driver of the diseases epidemiology. We reanalyzed data from those studies and found that all but one of the isolates from non-wheat hosts were members of PoT and the related Lolium-adapted lineage (PoL1), which meant that the Pyricularia populations typically found on endemic grasses had not yet been sampled. To address this shortcoming, we performed a comprehensive sampling of blast lesions in wheat crops and endemic grasses found in and away from wheat fields in Minas Gerais. A total 1,368 diseased samples were collected (976 leaves of wheat and grasses and 392 wheat heads) which yielded a working collection of 564 Pyricularia isolates. We show that, contrary to earlier implications, PoT was rarely found on endemic grasses and, conversely, members of grass-adapted populations were rarely found on wheat. Instead, most populations were host-specialized with constituent isolates usually grouping according to their host-of-origin. With regard to the dominant role proposed for signalgrass in wheat blast epidemiology, we found only one PoT member in 67 isolates collected from signalgrass grown away from wheat fields, and only three members of Urochloa-adapted populations among hundreds of isolates from wheat. Cross-inoculation assays on wheat and a signalgrass used in pastures (U. brizantha) suggested that the limited cross-infection observed in the field may be due to innate compatibility differences. Whether or not the observed level of cross-infection would be sufficient to provide an inoculum reservoir, or serve as a bridge between wheat growing regions, is questionable and, therefore, deserves further investigation.

microbiology↗

Dynamic Periodicity of Extended-Spectrum Cephalosporin Resistant Bloodstream Escherichia coli Infections Driven by Non-CC131 Strains

Extended-spectrum cephalosporin resistant Escherichia coli (ESC-R-Ec) is an urgent public health threat with sequence type clonal complex 131 (STc131), phylogroup B2 strains being particularly concerning as the dominant cause of ESC-R-Ec infections. To address the paucity of recent ESC-R-Ec molecular epidemiology data in the United States, we used whole genome sequencing (WGS) to fully characterize a large cohort of invasive ESC-R-Ec at a tertiary care cancer center in Houston, Texas collected from 2016-2020. During the study timeframe, there were 1154 index E. coli bloodstream infections (BSIs) of which 389 (33.7%) were ESC-R-Ec. Using time series analyses, we identified a temporal dynamic of ESC-R-Ec distinct from ESC-susceptible E. coli (ESC-S-Ec), with cases peaking in the last six months of the calendar year. WGS of 297 ESC-R-Ec strains revealed that while STc131 strains accounted for [~]45% of total BSIs, the proportion of STc131 strains remained stable across the study time frame with infection peaks driven by genetically heterogeneous ESC-R-Ec clonal complexes. BlaCTX-M variants accounted for most {beta}-lactamases conferring the ESC-R phenotype (89%; 220/248 index ESC-R-Ec), and amplification of blaCTX-M genes was widely detected in ESC-R-Ec strains, particularly in carbapenem non-susceptible, recurrent BSI strains. BlaCTX-M-55 was significantly enriched within phylogroup A strains, and we identified blaCTX-M-55 plasmid-to-chromosome transmission occurring across non-B2 strains. Our data provide important information regarding the current molecular epidemiology of invasive ESC-R-Ec infections at a large tertiary care cancer center and provide novel insights into the genetic basis of observed temporal variability for these clinically important pathogens. IMPORTANCEGiven that E. coli is the leading cause of worldwide ESC-R Enterobacterales infections, we sought to assess the current molecular epidemiology of ESC-R-Ec using a WGS analysis of many BSIs over a five-year period. We identified fluctuating temporal dynamics of ESC-R-Ec infections, which has also recently been identified in other geographical regions such as Israel. Our WGS data allowed us to visualize the stable nature of STc131 over the study period and demonstrate a limited, but genetically diverse group of ESC-R-Ec clonal complexes are detected during infection peaks. Additionally, we provide a widespread assessment of {beta}-lactamase gene copy number in ESC-R-Ec infections and delineate mechanisms by which such amplifications are achieved in a diverse array of ESC-R-Ec strains. These data suggest that serious ESC-R-Ec infections are driven by a diverse array of strains in our cohort and impacted by environmental factors suggesting that community-based monitoring could inform novel preventative measures.

microbiology↗

Pig herd management and infection transmission dynamics: a challenge for modellers.

The control of epidemics requires a thorough understanding of the complex interactions between pathogen transmission, disease impact, and population dynamics and management. Mechanistic epidemiological modelling is an effective way to address this issue, but handling highly structured and dynamic systems, remains challenging. We therefore developed a novel approach that combines Multi-Level Agent-Based Systems (MLABS) with spatial and temporal organization, allowing for a tuned representation of the transmission processes amongst the host population. We applied this method to model the spread of a PRRSv-like virus in pig farms, integrating the clinical consequences (conception and reproduction failures), in terms of animal husbandry practices. Results highlighted the importance to account for spatial and temporal structuring and herd management policies in epidemiological models. Indeed, disease-related abortions, inducing reassignments of sows in different batches, was shown to enhance the transmission process, favouring the persistence of the virus at the herd level. Supported by a declarative Domain-Specific Language (DSL), our approach provides flexible and powerful solutions to address the issues of on-farm epidemics and broader public health concerns. The present application, based on a simple Susceptible-Exposed-Infected-Recovered (SEIR) model, opens the way to the representation of more complex epidemiological systems, including more specific features such as maternally derived antibodies, vaccination, or dual infections, along with their respective clinical consequences on the management practices.

ecology↗

P-DOR, an easy-to-use pipeline to reconstruct outbreaks using pathogen genomics

Bacterial Healthcare Associated Infections (HAIs) are a major threat worldwide, which can be counteracted by establishing effective infection control measures, guided by constant surveillance and timely epidemiological investigations. Genomics is crucial in modern epidemiology but lacks standard methods and user-friendly software, accessible to users without a strong bioinformatics proficiency. To overcome these issues we developed P-DOR, a novel tool for rapid bacterial outbreak characterization. P-DOR accepts genome assemblies as input, it automatically selects a background of publicly available genomes using k-mer distances and adds it to the analysis dataset before inferring a SNP-based phylogeny. Epidemiological clusters are identified considering the phylogenetic tree topology and SNP distances. By analyzing the SNP-distance distribution, the user can gauge the correct threshold. Patient metadata can be inputted as well, to provide a spatio-temporal representation of the outbreak. The entire pipeline is fast and scalable and can be also run on low-end computers. Availability and implementationP-DOR is implemented in Python3 and R and can be installed using conda environments. It is available from GitHub https://github.com/SteMIDIfactory/P-DOR under the GPL-3.0 license.

microbiology↗

Detection and characterization of novel luchacoviruses, genus Alphacoronavirus, in meso-carnivores in the northeastern United States

Small to mid-sized carnivores, or meso-carnivores, comprise a group of diverse mammals, many of which can adapt to anthropogenically disturbed environments. Wild meso-carnivores living in urban areas may get exposed to or spread pathogens to other species, including stray/feral domestic animals. Several coronaviruses (CoVs) have been detected in domesticated and farmed meso-carnivores, but knowledge of CoVs circulating in free-ranging wild meso-carnivores remains limited. In this study, we analyzed 321 samples collected between 2016 and 2022 from 9 species of free-ranging wild meso-carnivores and stray/feral domestic cats in the northeastern United States. Using a pan-CoV PCR, we screened tissues, feces, and saliva, nasal, and rectal swabs. We detected CoV RNA in fecal and saliva samples of animals in four species: fisher (Pekania pennanti), bobcat (Lynx rufus), red fox (Vulpes vulpes), and domestic cat (Felis catus). Next-generation sequencing revealed that all these viruses belonged to the Luchacovirus subgenus (Alphacoronavirus genus), previously reported only in rodents and lagomorphs (i.e., rabbits). Genetic comparison of the 3-end of the genome ([~]12,000bp) revealed that although the viruses detected group with, and have a genetic organization similar to other luchacoviruses, they are genetically distinct from those from rodents and lagomorphs. Genetic characterization of the spike protein revealed that the meso-carnivore luchacoviruses do not have an S1/S2 cleavage motif but do have highly variable structural loops containing cleavage motifs similar to those identified in certain pathogenic CoVs. This study highlights the importance of characterizing the spike protein of CoVs in wild species for further targeted epidemiologic monitoring. ImportanceSeveral coronaviruses (CoVs) have been detected in domesticated, farmed, and wild meso-carnivores, causing a wide range of diseases, and infecting diverse species, highlighting their important but understudied role in the epidemiology of these viruses. Assessing the viral diversity hosted in wildlife species is essential to understand their significance in the cross-species transmission of CoVs. Our focus here was on CoV discovery in meso-carnivores in the Northeast USA as a potential "hotspot" area with high density of humans and urban wildlife. This study identifies novel alphacoronaviruses circulating in multiple free-ranging wild and domestic species in this area and explores their potential epidemiological importance based on regions of the Spike gene that are relevant for virus-host interactions.

microbiology↗

Rescue of Mycobacterium bovis DNA obtained from cultured strains during official surveillance of animal TB: key steps for robust whole genome sequence data generation

Epidemiological surveillance of animal tuberculosis (TB) based on whole genome sequencing (WGS) of Mycobacterium bovis has recently gained track due to its high resolution to identify infection sources, characterize the pathogen population structure, and for contact tracing. However, the workflow from bacterial isolation to sequence data analyses has several technical challenges that may severely impact the power to understand the epidemiological scenario and inform outbreak response. While trying to use archived DNA from cultured strains obtained during routine official surveillance of animal TB in Portugal, we struggled against three major challenges: the low amount of M. bovis DNA obtained from routinely processed animal samples; the lack of purity of M. bovis DNA, i.e. high levels of contamination with DNA from other organisms; and the co-occurrence of more than one M. bovis strain per sample (within-host mixed infection). The loss of an isolates genome is a missed link in transmission chain reconstruction, hampering the biological and epidemiological interpretation of data as a whole. Upon identification of these challenges, we implemented an integrated solution framework, based on whole genome amplification and a dedicated computational pipeline, to minimize their effects and recover as many genomes as possible. With the approaches described herein, we were able to recover 62 out of 100 samples that would have otherwise been lost. Based on these results, we discuss adjustments that should be made in official and research laboratories to facilitate sequential implementation of bacteriological culture, PCR, downstream genomics and computational-based methods. All of this in a time frame supporting data-driven intervention.

genomics↗

Selfish grower behavior can group-optimally eradicate plant diseases caused by coinfection

Game-theoretic behavioral and epidemiological models suggest that it is impossible to eradicate a disease through voluntary control actions when individuals behave according to their own interests. The simple reason is that free-riding behavior, which is best for self-interest, leads to a control coverage on the group level that is insufficient to eradicate the disease. Here we show that, for diseases that are caused by coinfection, selfinterest can actually result in the socially optimal outcome of disease eradication. Our result challenges the conventional wisdom that selfish behavior undermines the group interest; it resolves a social dilemma in the absence of any cooperation, institutional arrangements, or social norms. Our model is motivated by coinfecting plant viruses, common among agricultural crops and natural plants, and the behavioral dynamics of growers to adopt protective action (biological or chemical control). The epidemiological scenario, in which the disease is eradicated by self-interest, is characterized by a positive feedback process in which coinfection enhances infectivity. Similar feedback structures exist for a range of typical epidemiological processes that facilitate disease persistence if prevalence is sufficiently large. The underlying mechanism may therefore be applicable to other diseases.

ecology↗

A metagenomics-based survey of the virus diversity in mosquito vectors allows the first detection of Sindbis virus in Burkina Faso

Mosquito-borne viruses represent a threat to human health worldwide. This taxonomically-diverse group includes numerous viruses that recurrently spread into new regions. Thus, periodic surveillance of the arbovirus diversity in a given region can help optimizing the diagnosis of arboviral infections. Nevertheless, such screenings are rarely carried out, especially in low-income countries. Consequently, case investigation is often limited to a fraction of the arbovirus diversity. This situation probably results in undiagnosed cases. Here, we have explored the diversity of mosquito-borne viruses in two regions of Burkina Faso. To this end, we have screened mosquitoes collected along three years in six urban and rural areas using untargeted metagenomics. The analysis focused on two mosquito species, Aedes aegypti and Culex quinquefasciatus, considered among the main vectors of arboviruses worldwide. The screening detected Sindbis virus (SINV, Togaviridae) for the first time in Burkina Faso. This zoonotic arbovirus has spread from Africa into Europe. SINV causes periodic outbreaks in Europe but its distribution and epidemiology in Africa remains largely unstudied. SINV was detected in one of the six areas of the study, and at a single year. Detection was validated with isolation in cell culture. SINV was only detected in Cx. quinquefasciatus, thus extending the list of potential vectors of SINV in nature. SINV infection rate in mosquitoes was similar to those observed in European regions that experience SINV outbreaks. A phylogenetic analysis placed the nearly-full genome within a cluster of Central African strains of lineage I. This cluster is supposedly at the origin of the SINV strains introduced into Europe. Thus, West Africa should also be considered as a potential source of the European SINV strains. Our results call for studies on the prevalence of SINV infections in the region to estimate disease burden and the interest of SINV diagnostic in case investigation. Author summaryMosquito-borne viruses are responsible for millions of cases worldwide every year. Moreover, they have repeatedly shown an ability to spread over large distances. Thus, periodic surveys of the arbovirus diversity in a given region can help to define the diagnostic tests to use during case investigation. However, comprehensive surveys are rarely carried out, especially in low-income countries. Here, the arbovirus diversity was assessed in two main mosquito vectors in Burkina Faso using untargeted metagenomics. This screening identified Sindbis virus (SINV), a zoonotic arbovirus, for the first time in Burkina Faso. Moreover, SINV was found in nature for the first time in Culex quinquefasciatus, a main mosquito vector of several pathogens and with a cosmopolitan distribution. SINV leads to periodic outbreaks mainly in Europe. Despite a likely African origin, its distribution and epidemiology in Africa remains largely unstudied. The SINV sequence from Burkina Faso felt within the cluster of Central African strains thought to be at the origin of the European SINV strains. Thus, our results indicate that West Africa should be considered as another potential source of the SINV introductions in Europe. Further studies are required to characterize SINV epidemiology in Burkina Faso and the West African region.

microbiology↗

Systematic bias in malaria parasite relatedness estimation

Genetic studies of malaria parasites increasingly feature estimates of relatedness. However, various aspects of malaria parasite relatedness estimation are not fully understood. For example, estimates of relatedness based on whole-genome-sequence (WGS) data often exceed those based on more sparse data types. We explore systematic bias in relatedness estimation using theoretical, numerical and empirical approaches. Specifically, we use a non-ancestral model of pairwise relatedness to derive theoretical results; a simulation model of ancestry to independently verify and expand our theoretical results; and data on parasites sampled from Guyana to explore how theoretical and numerical results translate empirically. We show that allele frequencies encode, locus-by-locus, relatedness averaged over the set of sampled parasites used to compute them. These sample allele frequencies are typically plugged into the models used to estimate pairwise relatedness. Consequently, models of pairwise relatedness are misspecified and pairwise relatedness values are systematically underestimated. However, systematic underestimation can be viewed as population-relatedness calibration, i.e., a way of generating measures of relative relatedness. Systematic underestimation is unavoidable when relatedness is estimated assuming independence between genetic markers. It is mitigated when estimated using WGS data under a hidden Markov model (HMM), which exploits linkage between proximal markers. Estimates of absolute relatedness generated under a HMM using relatively sparse data should be treated with caution because the extent to which underestimation is mitigated is unknowable. That said, analyses dependent on absolute values and high relatedness thresholds are relatively robust. In summary, practitioners have two options: resolve to use relative relatedness estimated under independence or try to estimate absolute relatedness under a HMM. We propose various practical tools to help practitioners evaluate their situation on a case-by-case basis. Author summaryMalaria genomic epidemiology is increasingly recognised as a tool for public health. Relatedness, which captures likeness derived from common ancestry, is a useful concept for malaria parasites. Analyses of malaria parasite relatedness are important for generating results on spatiotemporal scales relevant to disease control. Since shared ancestry is unobservable, relatedness must be estimated under a statistical model. However, not all aspects of malaria parasite estimation are fully understood, including the effects of different data types. In this work, we characterise systematic biases in estimates of malaria parasite relatedness. Our analysis is three-fold: we mathematically interrogate a non-ancestral model of relatedness to derive theoretical results; simulate parasite ancestries from first principles to yield numerical results; and perform an empirical case study of parasites sampled from Guyana. We show that bias may be particularly pronounced when using sparse marker data from inbred parasite populations, which are often found in pre-elimination settings. We chart out a practical roadmap to enable practitioners to assess epidemiological settings on a case-by-case basis. Our findings are relevant to applications in malaria genomic epidemiology that use relatedness directly or indirectly, including molecular surveillance and the genetic-based classification of treatment failure.

genetics↗

The utility of whole-genome sequencing to identify likely transmission pairs for pathogens with slow and variable evolution

Pathogen whole-genome sequencing (WGS) has been used to track the transmission of infectious diseases in extraordinary detail, especially for pathogens that undergo fast and steady evolution, as is the case with many RNA viruses. However, for other pathogens evolution is less predictable, making interpretation of these data to inform our understanding of their epidemiology more challenging and the value of densely collected pathogen genome data uncertain. Here, we assess the utility of WGS for one such pathogen, in the "who-infected-whom" identification problem. We study samples from hosts (130 cattle, 111 badgers) with confirmed infection of M. bovis (causing bovine Tuberculosis), which has an estimated clock rate as slow as [~]0.1-1 variations per year. For each potential pathway between hosts, we calculate the relative likelihood that such a transmission event occurred. This is informed by an epidemiological model of transmission, and host life history data. By including WGS data, we shrink the number of plausible pathways significantly, relative to those deemed likely on the basis of life history data alone. Despite our uncertainty relating to the evolution of M. bovis, the WGS data are therefore a valuable adjunct to epidemiological investigations, especially for wildlife species whose life history data are sparse.

ecology↗

Revisiting typing systems for group B Streptococcus (GBS) prophages: an application in prophage detection and classification in GBS isolates from Argentina

Group B Streptococcus (GBS) causes severe infections in neonates and adults with comorbidities. Prophages have been reported to contribute to GBS evolution and pathogenicity. However, no studies are available to date on the presence and diversity of prophages in GBS isolates from humans in South America. This study provides insights into the prophage content of 365 GBS isolates collected from clinical samples in the context of an Argentinean multicentric study. Using whole genome sequence data, we implemented two previously proposed methods for prophage typing: a PCR approach (carried out in silico) coupled with a blastx-based method to classify prophages based on their prophage group and integrase type, respectively. We manually searched the genomes and identified 325 prophages. However, only 80% of prophages could be accurately categorised with the previous approaches. Integration of phylogenetic analysis, prophage group and integrase type allowed for all to be classified into 19 prophage types, which correlated with GBS clonal complex grouping. The revised prophage typing approach was additionally improved by using a blastn search after enriching the database with 10 new genes for prophage group classification combined with the existing integrase typing method. This modified and integrated typing system was applied to the analysis of 615 GBS genomes (365 GBS from Argentina and 250 from public databases), which revealed 29 prophage types, including 2 novel integrase subtypes. Their characterization and comparative analysis revealed major differences in the lysogeny and replication modules. Genes related to bacterial fitness, virulence or adaptation to stressful environments were detected in all prophage types. Considering prophage prevalence, distribution and their association with bacterial virulence, it is important to study their role in GBS epidemiology. In this context, we propose the use of an improved and integrated prophage typing system suitable for rapid phage detection and classification with little computational processing. Author summaryBacteriophages, which are viruses that infect bacteria, exert a profound influence on microbial evolution when integrated into the bacterial genome, a state in which they are called prophages. It has been proposed that prophage acquisition played a role in the emergence of Streptococcus agalactiae (GBS) as a human pathogen in European countries. Further study and characterization of prophages of GBS from around the world would provide valuable insights into the mechanisms underlying GBS adaptation, evolution and epidemiology. Unfortunately, existing tools for prophage screening exhibit limitations in the detection and classification of all prophages present in GBS genomes. To address this issue, in this work we propose a new prophage typing system that allows the detection and classification of GBS prophages based on both their phylogenetic lineage and integration site within the bacterial genome. Using this methodology we were able to identify 29 prophage types in 615 GBS isolated globally. We further characterised these prophages and found that they carried genes that could give an evolutionary advantage to their host and that different lineages of GBS carried different prophage types. Comprehensive exploration and characterization of prophages represent an indispensable endeavour, providing critical insights into microbial evolution, epidemiology, and potential therapeutic interventions.

bioinformatics↗

Biological tick control: modeling the potential impact of entomopathogenic fungi on the transmission of East Coast fever in cattle

Biological control of ticks using entomopathogenic fungi (EPF) is a highly desired alternative to chemical acaricides for the control of tick-borne pathogens. For Metarhizium anisopliae isolate ICIPE 7, one of these EPFs, efficacy against multiple tick species has been demonstrated in laboratory and field settings. However, we currently have little quantitative understanding of how EPFs can impact transmission. We developed a deterministic model of tick-host-pathogen interactions to explore how the effects of EPF on Rhipicephalus appendiculatus ticks may impact the transmission dynamics of East Coast fever (ECF) in cattle populations. We parameterized the multi-faceted effects of EPFs on tick dynamics using experimental data on Tickoff(R) biopesticide (a novel formulation of M. anisopliae ICIPE 7) and related EPFs. The epidemiological impact of EPF was evaluated across a range of product profiles and implementation strategies. Model results indicate that, for the explored product profiles, EPF derives most of its epidemiological impact through the delayed mortality effect. This EPF-induced mortality could not only reduce the onward Theileria parva transmission to cattle (both treated and untreated) but could also cause a reduction in the tick-to-host ratio and thus cattle exposure to ticks. The effects of EPF on reproduction fitness and engorgement of ticks elicit negligible impact. High levels of population coverage and treatment frequency are needed to reduce the tick population size and reach meaningful epidemiological impact in cattle populations. Additionally, increasing the persistence time of fungal conidia on cattle skin - through technological improvements to the EPF formulation - can substantially reduce acute infections when combined with appreciable population coverage levels, treatment frequency, and efficient spraying techniques. Our model analysis provides insights into the potential impact of EPF when deployed at a population level, and lends support to further research and development of this biological tick control tool.

microbiology↗

DoubleTrouble: Multiple infections and the coevolution of virulence-resistance in structured host-parasite populations.

Parasite competition is a key factor driving the epidemiology and evolution of parasites, and is expected to modulate the selective pressures acting upon the host, and to alter its response to infection. Using a nested co-evolutionary model where epidemiological traits (transmission, virulence and recovery) are derived from within-host interactions between parasite strains, we analyse using adaptive dynamics methodology the joint evolution of parasite virulence and host resistance. We compare the predicted coevolutionarily stable states under different competition regimes, including single infections (preemption), superinfection (strain dominance) and coinfections (transient strain coexistence). We find that coinfections select for lower virulence compared to superinfection, while the opposite trend is observed for host resistance. The local coexistence of parasites in coinfected hosts creates a kin selection effect that reduces both parasite virulence and host response. We show that the magnitude of this effect depends on the ecological context, and notably the degree of coupling between hosts. Our work contributes to building the gap between metapopulation ecology and epidemiology.

evolutionary biology↗

This is SPRTA: assessing phylogenetic confidence at pandemic scales

Phylogenetics plays a central role in evolutionary biology and genomic epidemiology. Assessing phylogenetic confidence and reliability is therefore crucial and methods to do this, such as Felsensteins bootstrap, are among the most used in modern science. However, methods based on Felsensteins bootstrap suffer from excessive computational demand, and are unsuitable for large datasets. Furthermore, most of these methods emerge from a cladistic framework which makes their results hard to interpret in the context of genomic epidemiology. We propose SPRTA (" SPR-based Tree Assessment"), an efficient and interpretable approach to assess confidence in phylogenetic trees. SPRTA shifts the paradigm of phylogenetic support measurement from evaluating the confidence in clades (groupings of taxa) to genome evolution histories, for example assessing if a lineage evolved from another considered lineage or not. This focus on evolutionary histories is particularly valuable in genomic epidemiology, where typically the evolutionary and transmission history of a pathogen are of interest, not clade content. We illustrate the use of SPRTA by investigating a global SARS-CoV-2 phylogenetic tree relating > 2M genomes, highlighting plausible alternative evolutionary origins of many SARS-CoV-2 variants. We have implemented SPRTA within the free and open source maximum likelihood phylogenetic software MAPLE, available from https://github.com/NicolaDM/MAPLE.

bioinformatics↗

Parapipe: a Pipeline for Handling Parasite NGS Datasets and its Application to Cryptosporidium

0.0Cryptosporidium, a protozoan parasite of significant public health concern, is responsible for severe diarrheal diseases, particularly in immunocompromised individuals and young children in resource-limited settings. Analysis of whole genome next generation sequencing (NGS) data is a critical next step in improving our understanding of Cryptosporidium epidemiology, transmission dynamics, and genetic diversity. However, effective analysis of NGS data in a public health context necessitates the development of robust, validated bioinformatics tools. Here, we present Parapipe, a modular ISO accreditable bioinformatics pipeline designed for high-throughput processing and analysis of Cryptosporidium NGS datasets. Built using Nextflow DSL2 and containerized with Singularity, Parapipe is portable, scalable, and capable of end-to-end analyses, including quality control, variant calling, multiplicity of infection (MOI) investigations and phylogenomic clustering analysis. Using both simulated and real-world datasets, we demonstrate Parapipes ability to resolve genetic heterogeneity, identify mixed infections, and generate high-resolution phylogenomic insights. Here, we use it to carry out a comparison between whole genome single nucleotide polymorphism (wgSNP) typing and the conventionally used gp60 molecular typing scheme. Compared to existing pipelines, Parapipe uniquely integrates MOI analysis, enabling the differentiation of mixed infections and supporting epidemiological investigations. Parapipes design facilitates integration with geographic, demographic, epidemiological and environmental data, enhancing its utility for tracking transmission pathways and outbreak sources. Parapipe represents a significant advance in utilising genomics for public health surveillance of Cryptosporidium, offering a streamlined and reproducible framework for analysis with potential application to other pathogenic protozoa. By automating complex workflows and enabling detailed genomic characterization, Parapipe provides a valuable tool for public health agencies and researchers, supporting efforts to mitigate the global burden of cryptosporidiosis.

bioinformatics↗

A public resource of 15 genomically characterised representative strains of Shigella sonnei

Shigella sonnei is rapidly emerging as the dominant agent of shigellosis, an enteric disease responsible for a significant burden of morbidity and mortality worldwide. Whole-genome sequencing of S. sonnei isolated over the last three decades has revealed phylogenomic diversity within the population and the emergence of multiple lineages associated with distinct epidemiological patterns such as resistance to critical antimicrobials and/or transmission within different groups. However most experimental work on S. sonnei biology and pathogenicity has focused on a single laboratory strain (53G), which is phylogenetically distant from currently circulating strains. Here we introduce a set of 15 phylogenetically diverse and epidemiologically relevant S. sonnei isolates made available through publicly accessible culture collections as a resource for laboratory science. We present their complete whole-genome sequences, including the pINV invasion plasmid (missing from a large proportion of public genome data due to loss during laboratory culture). Finally, the characterisation and comparison of these complete genome sequences highlight evidence for ongoing adaptive evolution in S. sonnei, featuring the accumulation of insertion sequences, gene pseudogenisation and structural variation. Significance as a BioResource to the communityGenomic analysis of Shigella has historically been challenging due to presence of hundreds of repetitive sequence elements (which can cause fragmented assemblies) and loss of the pINV invasion plasmid (essential to virulence) during laboratory culture. Furthermore, most experimental work on S. sonnei pathogenicity uses a lab strain that is phylogenetically distant from circulating isolates. To support S. sonnei experimental and in silico research and increase its relevance to current clinical problems, we report here the complete, high-quality genome sequences of 15 S. sonnei isolates, each selected to represent distinct sub-clades of epidemiological interest. We also make the corresponding strains publicly available in national reference culture collections. Data summaryAll sequencing reads and complete assemblies have been deposited into the National Center for Biotechnology Information (NCBI) database (accessions to be determined). Genome assemblies and Bakta annotations used in the analysis can be found in Figshare (https://doi.org/10.6084/m9.figshare.28302986) together with Mauve multiple-sequence alignments for the chromosome and pINV plasmid sequences, and genome-scale metabolic models produced for each strain. Pure cultures of all strains were deposited in the publicly accessible National Collection of Type Cultures (NCTC, UK) or the "Collection de lInstitut Pasteur" (CIP, France) (accessions to be determined).

microbiology↗

Aedes albopictus is rapidly invading its climatic niche in France: wider implications for biting nuisance and arbovirus control in Western Europe

The Asian tiger mosquito, Aedes albopictus, is a competent vector of arboviruses, such as dengue. After its introduction into southern Europe, this invasive species has been rapidly spreading as well as causing autochthonous cases of arboviral diseases. Both Ae. albopictus presence and potential to transmit arboviruses are facilitated at warm temperatures, hence global warming is expected to affect their presence in temperate regions. We use a climate- and environmental-driven mechanistic modelling framework to investigate the impact of recent climate change on Ae. albopictus range expansion and its potential to transmit dengue in Western Europe. We simulate climatic suitability, adult density and dengue transmission risk which we compare with a large ensemble of entomological and epidemiological observations over the past 20 years. Most importantly, we analyze a novel spatiotemporal dataset of colonized municipalities in metropolitan France to estimate the spread rate of Ae. albopictus and compare it with model predictions. Lastly, we analyze the sensitivity of entomological and epidemiological risk to changes in temperature, rainfall and human density. Distribution of simulated mosquito populations and dengue transmission risk satisfactorily match entomological and dengue observations for Western Europe (AUC = 0.90 and 0.75 respectively). While lowlands in southern Europe were already climatically suitable for hosting Ae. albopictus around 2010, Western France, together with large populated cities, such as London, Zagreb and Vienna, have become suitable recently. Importantly, the accelerating colonization of Ae. albopictus in France may be approaching the limit of its theoretical climatic niche; future expansion will depend on the climate-driven enlargement of suitable areas. Area at risk of dengue transmission has recently expanded from the Mediterranean coasts over northern Spain and Western France. The sensitivity analysis suggests that climate change may expose medium-sized cities to the highest epidemiological risk; this finding is consistent with recently reported dengue outbreaks in Europe.

ecology↗