Biology subjects

Hill, V.

Publications and source records attributed to Hill, V..

14 recordsLinked to original sources

bioRxiv2026

Tracking two decades of global dengue virus lineage dynamics

Dengue virus (DENV) is genetically diverse, consisting of four antigenically distinct serotypes and extensive sub-serotype variation that can influence epidemiology and control. As DENV continues to expand globally, there is an urgent need to characterize the dynamics of distinct DENV genetic lineages, including their persistence, establishment, and spread. Using a standardized DENV lineage nomenclature system and 37,828 publicly available DENV genomes sampled from 2000-2024, we classified sequences across nine global regions to construct a comprehensive resource of regional lineage distributions over time. We found marked regional differences in lineage diversity, with higher lineage richness in Southeast and East Asia than in the Americas. We further showed that COVID-19-related disruptions were associated with decreased regional lineage persistence and detection of new lineages during 2020-2021, followed by rebounds after 2022 and, in some regions, substantial lineage turnover. Finally, we identified a small set of globally expansive (cosmopolitan) lineages that are over-represented in available sequences, including five first-order minor lineages detected in at least seven of nine regions: 3III_B.3, 2II_F.1, 2II_A.1, 1III_A.3, and 1I_K.3. Together, these results demonstrate how standardized lineage classification enables global tracking of emerging DENV diversity and supports targeted genomic surveillance.

bioinformatics↗

bioRxiv2026

Phylodynamic analysis reveals asymmetric and accelerating global spread of dengue virus

Dengue virus (DENV) continues to expand globally, with increasing incidence in both endemic and non-endemic countries. Leveraging a large global dataset of DENV genomes starting from the 1940s, we reconstructed global and regional patterns of DENV spread using phylogeographic and phylodynamic methods. Our analyses reveal that the current global diversity of urban DENV originated in Asia in the first half of the 20th century. During the more than 100 years since, we find that the highest density of between-country spread occurs within Asia and the region continues to be a global source, seeding transmission in Africa and the Americas. Global spread is, however, not balanced. Even though there is more travel to South America, we show that DENV lineages primarily enter North America (mostly from South Asia) through a link defined by seasonal synchrony across the Northern Hemisphere. Along with a substantial increase in global travel starting ~2010, the rate of spread to the Americas is increasing, establishing new lineages associated with large recent outbreaks. DENV lineages do not frequently spread back to Asia from the Americas or Africa, and we posit this is due to higher genetic diversity in Asia, leading to stiffer competition for invading lineages. Within the Americas, the network of DENV dispersal initiates in North America, primarily the Caribbean, and then is maintained by major hubs in South America. Overall, we find that travel volume, rather than climate factors, is mostly responsible for long-term patterns of DENV spread globally and within the Americas. Our results highlight key nodes in the global dynamics of DENV lineages, and suggest spread will continue to accelerate in a more connected world.

genomics↗

bioRxiv2026

Evolutionary history of Jamestown Canyon virus disentangles complex multi-vector ecology

Jamestown Canyon virus (JCV) is a re-emerging mosquito-borne virus of increasing concern in North America. It has been historically understudied, leading to significant gaps in our understanding of its evolutionary history, ecological maintenance, and transmission dynamics. Here, we generated 658 whole-genome JCV sequences from the Northeast United States, including 84% (500/597) of all JCV-positive mosquitoes detected in Connecticut from 1997-2022. Then we applied phylodynamic methods to demonstrate how mosquito phenology and host interaction structure the persistence and spread of JCV. Our phylogenetic analyses estimate that JCV was introduced in the Northeast by at least the early 1700s and the primary introductions of lineages A and B into Connecticut occurred during the mid-1800s to mid-1900s. Further, we estimate that JCV evolves at a rate of [~]3 x 10-5 s/s/y, making it one of the slowest evolving known RNA viruses, because the virus spends [~]10 months per year in evolutionary stasis while over-wintering in mosquito eggs. To investigate ecological drivers of JCV spread in Connecticut, we paired discrete trait and continuous phylogeographic reconstructions with mosquito surveillance data. We estimate that JCV has a low diffusion rate of [~]30-60 km2/year, which is more similar to slow-moving tick-borne viruses than other mosquito-borne viruses. We found that univoltine Aedes mosquitoes were likely to maintain the virus across years through overwintering in eggs, accounting for its slow evolution and dispersal, while multivoltine mosquitoes contribute to periodic bursts of spatial diffusion and amplification within seasons. By characterizing seasonal dynamics of JCV, we demonstrate the utility of dense sequencing and phylodynamics to disentangle complex transmission cycles, offering a framework to rapidly advance our evolutionary and ecological knowledge of understudied viruses.

ecology↗

bioRxiv2025

Heterogeneity in inhibition of genetically diverse dengue virus strains by Wolbachia

The release of Aedes aegypti mosquitoes transinfected with the virus-inhibiting Wolbachia bacterium has the potential to reduce the burden caused by dengue virus (DENV). However, the robustness of this control strategy across the wide genetic diversity of DENV remains unknown. Here, we systematically tested two commonly used Wolbachia strains (wAlbB and wMelM) for their ability to inhibit 60 genetically diverse DENV isolates spanning all four serotypes. We found stronger inhibition by wMelM (median relative dissemination: 0.04) than wAlbB (median relative dissemination: 0.19). Furthermore, while we found substantial heterogeneity in inhibition across DENV isolates, we found that more DENV-3 isolates were weakly inhibited (median relative dissemination: 0.47 for wAlbB and 0.39 for wMelM) compared to the other serotypes (median relative disseminations: 0.10-0.18 for wAlbB and 0-0.11 for wMelM). Using transmission dynamic models, we further showed that differential Wolbachia inhibition results in increased probability of reemergence, particularly in high transmission intensity settings, with strong selection for DENV strains that have higher relative dissemination in mosquitoes. Our work highlights the importance of considering DENV genetic diversity, including the long-term risk of selection, in Wolbachia-based control interventions.

microbiology↗

bioRxiv2025

Unraveling Dengue Serotype 3 Transmission in Brazil: Evidence for Multiple Introductions of the 3III_B.3.2 Lineage

Dengue, caused by DENV 1-4, remains a global public health concern, with Brazil experiencing some of the largest epidemics. The reemergence of DENV-3 in Brazil between 2023 and 2024 has raised concerns about new outbreaks due to the absence of sustained circulation of this serotype in recent years. This study investigates the dynamics of DENV-3 in Brazil, focusing on the spread of the 3III_B.3.2 lineage within genotype 3III and its introduction routes. We analyzed 1,536 DENV-3 genomes, all classified as genotype 3III, the dominant DENV-3 genotype in Brazil since 2001. Phylogenetic analysis identified the 3III_B.3.2 lineage in all recent Brazilian cases, with detections also reported in Central America, the United States, and Europe. At least six independent introduction events of this lineage into Brazil were identified, with the Caribbean region and Costa Rica as the primary sources. The earliest introduction likely occurred in late 2022 in Roraima, followed by introductions in Sao Paulo, Minas Gerais, and Para. While one instance of interstate transmission was detected -- from Sao Paulo to Minas Gerais -- our findings indicate that external introductions, rather than domestic spread, were the primary drivers of DENV-3 circulation during this period. These results underscore the importance of continued genomic surveillance and coordinated public health strategies to monitor and mitigate future outbreaks.

bioinformatics↗

bioRxiv2024

Large-scale genomic analysis of SARS-CoV-2 Omicron BA.5 emergence in the United States

The COVID-19 pandemic is marked by the continuing emergence of novel SARS-CoV-2 variants. Questions remain about the mechanisms with which these lineages establish themselves in new geographical areas. In this study, we performed a discrete phylogeographic analysis on [~]19,000 SARS-CoV-2 sequences of Omicron BA.5 lineages between February and June 2022 to better understand how it emerged in different regions of the United States (U.S.). We found that the earliest introductions came from Africa, the putative origin of the variant, but the majority were from Europe, correlating with the high volume of air travelers. Additionally, the analysis revealed extensive domestic transmission between different regions of the U.S. driven by population size and cross-country transmission. Results suggest that most of the within-U.S. spread was between three regions that include California, New York, and Florida. Our results form a framework for understanding novel SARS-CoV-2 variant emergence in the U.S.

genomics↗

bioRxiv2024

Performance of GPT-4 on the American College of Radiology In-Service Examination

ObjectivesNo study has evaluated the ability of ChatGPT-4 to answer image-rich diagnostic radiology board exam questions or assessed for model drift in GPT-4s image interpretation abilities. In our study we evaluate GPT-4s performance on the American College of Radiology (ACR) 2022 Diagnostic Radiology In-Training Examination (DXIT). MethodsQuestions were sequentially input into GPT-4 with a standardized prompt. Each answer was recorded and overall accuracy was calculated, as was logic-adjusted accuracy, and accuracy on image-based questions. This experiment was repeated several months later to assess for model drift. ResultsGPT-4 achieved 58.5% overall accuracy, lower than the PGY-3 average (61.9%) but higher than the PGY-2 average (52.8%). Adjusted accuracy was 52.8%. GPT-4 showed significantly higher (p = 0.012) confidence for correct answers (87.1%) compared to incorrect (84.0%). Performance on image-based questions was notably poorer (p < 0.001) at 45.4% compared to text-only questions (80.0%), with adjusted accuracy for image questions of 36.4%. When the questions were repeated, GPT-4 chose a different answer 25.5% of the time and there was a small but insignificant decrease in accuracy. DiscussionGPT-4 performed between PGY-2 and PGY-3 levels on the 2022 DXIT, but significantly poorer on image-based questions, and with large variability in answer choices across time points. This study underscores the potential and risks of using minimally-prompted general AI models in interpreting radiologic images as a diagnostic tool. Implementers of general AI radiology systems should exercise caution given the possibility of spurious yet confident responses.

bioinformatics↗

bioRxiv2022

The origins and molecular evolution of SARS-CoV-2 lineage B.1.1.7 in the UK

The first SARS-CoV-2 variant of concern (VOC) to be designated was lineage B.1.1.7, later labelled by the World Health Organisation (WHO) as Alpha. Originating in early Autumn but discovered in December 2020, it spread rapidly and caused large waves of infections worldwide. The Alpha variant is notable for being defined by a long ancestral phylogenetic branch with an increased evolutionary rate, along which only two sequences have been sampled. Alpha genomes comprise a well-supported monophyletic clade within which the evolutionary rate is more typical of SARS-CoV-2. The Alpha epidemic continued to grow despite the continued restrictions on social mixing across the UK, and the imposition of new restrictions, in particular the English national lockdown in November 2020. While these interventions succeeded in reducing the absolute number of cases, the impact of these non-pharmaceutical interventions was predominantly to drive the decline of the SARS-CoV-2 lineages which preceded Alpha. We investigate the only two sampled sequences that fall on the branch ancestral to Alpha. We find that one is likely to be a true intermediate sequence, providing information about the order of mutational events that led to Alpha. We explore alternate hypotheses that can explain how Alpha acquired a large number of mutations yet remained largely unobserved in a region of high genomic surveillance: an under-sampled geographical location, a non-human animal population, or a chronically-infected individual. We conclude that the last hypothesis provides the best explanation of the observed behaviour and dynamics of the variant, although we find that the individual need not be immunocompromised, as persistently-infected immunocompetent hosts also display a higher within-host rate of evolution. Finally, we compare the ancestral branches and mutation profiles of other VOCs to each other, and identify that Delta appears to be an outlier both in terms of the genomic locations of its defining mutations, and its lack of rapid evolutionary rate on the ancestral branch. As new variants, such as Omicron, continue to evolve (potentially through similar mechanisms) it remains important to investigate the origins of other variants to identify ways to potentially disrupt their evolution and emergence.

evolutionary biology↗

bioRxiv2021

Making Genomic Surveillance Deliver: A Lineage Classification and Nomenclature System to Inform Rabies Virus Elimination

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 disease control. Previous studies have described the evolutionary history of rabies virus; however, the resulting taxonomy lacks the definition necessary to identify incursions, lineage turnover and transmission routes at high resolution. Here we propose a lineage classification system based on the dynamic nomenclature used for SARS-CoV-2, defining a lineage by phylogenetic methods, for tracking virus spread and comparing sequences across geographic areas. We demonstrate this system through application to the globally distributed Cosmopolitan clade of rabies virus, defining 73 total lineages within the clade, beyond the 22 previously reported. We further show how integration of this tool with a new rabies virus sequence data resource (RABV-GLUE) enables rapid application, for example, highlighting lineage dynamics relevant to control and elimination programmes, such as identifying importations and their sources, and areas of persistence and transmission, including transboundary incursions. This system and the tools developed should be useful for coordinating and targeting control programmes and monitoring progress as we work towards eliminating dog-mediated rabies, as well as having potential for broad application to the surveillance of other viruses. Author SummaryThe importance of the ability to track the diversity and spread of viruses in a universal way that can be clearly communicated has been highlighted during the SARS-CoV-2 pandemic. This, accompanied with the increase in the availability and use of pathogen sequence data, means the development of new genomic tools and classification systems can strengthen outbreak response and disease control. Here, we present an easy-to-use objective and transferable classification tool for tracking viruses at high resolution. We use rabies virus, a neglected zoonotic disease that causes around 59,000 human deaths each year, as an example use case of this tool. Applying our tool to a global clade of rabies virus, we find an over 200% increase in the definition at which we can classify the virus, allowing us to identify areas of persistence and transmission that were not previously apparent, and patterns of virus spread. Insights from the application of this tool should prove valuable in targeting vaccination campaigns and improving surveillance as countries work towards the elimination of dog-mediated rabies.

genomics↗

bioRxiv2021

Minimalistic mycoplasmas harbor different functional toxin-antitoxin systems

Mycoplasmas are minute bacteria controlled by very small genomes ranging from 0.6 to 1.4 Mbp. They lack a cell wall and have been suggested to have progressed through reductive evolution from phylogenetically closely related Clostridia. They are known to colonize the respiratory tract or the urogenital tract among other organs and can cause chronic and subclinical diseases associated with long persistence of the causative agent. Toxin-antitoxin systems (TAS) are genetic elements that have been described for several respiratory and urogenital pathogens as well as for Clostridia, but never for pathogenic mycoplasmas. Here we describe for the first-time different types of TAS in a Mycoplasma pathogen, namely M. mycoides subsp. capri. We identified candidate TAS in silico via TASmania database. Two candidate TAS identified in silico and another candidate TAS suggested in a minimal cell based on transposon mutagenesis were systematically tested for their functionality in hosts with different phylogenetic distance using heterologous expression. Phylogenetic distance of the host used for heterologous expression influenced the outcome of the functional testing. We corroborated functionality of the three candidate TAS in Mycoplasma capricolum subsp. capricolum. Moreover, we confirmed transcription and translation of molecules of the TAS investigated during in vitro growth. We sequence analyzed 15 genomes of M. mycoides subsp. capri and revealed an unequal distribution of the TAS studied pointing towards dynamic gain and loss of TAS within the species. Author summaryMycoplasmas have a minimal genome and have never been shown to possess TAS. In this work we showed the presence of different functional TAS systems in Mycoplasma mycoides subsp. capri, a caprine pathogen for the first time. Sequence analysis of a number of Mycoplasma mycoides subsp. capri strains revealed a plasticity of the genome with respect to TAS carriage. This work paves the way to investigate the biological role of TAS (e.g. persistence, stress tolerance) during infection using mycoplasmas as a simple model organism. Since most mycoplasmas lack classical virulence factors such as exotoxins and go into a kind of stealth mode to evade the immune system, TAS are likely to contribute to the parasitic lifestyle of mycoplasmas and should be investigated in that respect. The availability of synthetic genomics tools to modify a range of Mycoplasma pathogens and well-established challenge models for the latter mycoplasmas will foster future research on TAS in mycoplasmas.

microbiology↗

bioRxiv2020

Accommodating individual travel history, global mobility, and unsampled diversity in phylogeography: a SARS-CoV-2 case study.

Spatiotemporal bias in genome sequence sampling can severely confound phylogeographic inference based on discrete trait ancestral reconstruction. This has impeded our ability to accurately track the emergence and spread of SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Despite the availability of unprecedented numbers of SARS-CoV-2 genomes on a global scale, evolutionary reconstructions are hindered by the slow accumulation of sequence divergence over its relatively short transmission history. When confronted with these issues, incorporating additional contextual data may critically inform phylodynamic reconstructions. Here, we present a new approach to integrate individual travel history data in Bayesian phylogeographic inference and apply it to the early spread of SARS-CoV-2, while also including global air transportation data. We demonstrate that including travel history data for each SARS-CoV-2 genome yields more realistic reconstructions of virus spread, particularly when travelers from undersampled locations are included to mitigate sampling bias. We further explore methods to ameliorate the impact of sampling bias by augmenting the phylogeographic analysis with lineages from undersampled locations in the analyses. Our reconstructions reinforce specific transmission hypotheses suggested by the inclusion of travel history data, but also suggest alternative routes of virus migration that are plausible within the epidemiological context but are not apparent with current sampling efforts. Although further research is needed to fully examine the performance of our travel-aware phylogeographic analyses with unsampled diversity and to further improve them, they represent multiple new avenues for directly addressing the colossal issue of sample bias in phylogeographic inference.

evolutionary biology↗

bioRxiv2020

The emergence of SARS-CoV-2 in Europe and the US

Accurate understanding of the global spread of emerging viruses is critically important for public health response and for anticipating and preventing future outbreaks. Here, we elucidate when, where and how the earliest sustained SARS-CoV-2 transmission networks became established in Europe and the United States (US). Our results refute prior findings erroneously linking cases in January 2020 with outbreaks that occurred weeks later. Instead, rapid interventions successfully prevented onward transmission of those early cases in Germany and Washington State. Other, later introductions of the virus from China to both Italy and Washington State founded the earliest sustained European and US transmission networks. Our analyses reveal an extended period of missed opportunity when intensive testing and contact tracing could have prevented SARS-CoV-2 from becoming established in the US and Europe.

genetics↗

bioRxiv2020

A dynamic nomenclature proposal for SARS-CoV-2 to assist genomic epidemiology

The ongoing pandemic spread of a novel human coronavirus, SARS-COV-2, associated with severe pneumonia disease (COVID-19), has resulted in the generation of thousands of virus genome sequences. The rate of genome generation is unprecedented, yet there is currently no coherent nor accepted scheme for naming the expanding phylogenetic diversity of SARS-CoV-2. We present a rational and dynamic virus nomenclature that uses a phylogenetic framework to identify those lineages that contribute most to active spread. Our system is made tractable by constraining the number and depth of hierarchical lineage labels and by flagging and declassifying virus lineages that become unobserved and hence are likely inactive. By focusing on active virus lineages and those spreading to new locations this nomenclature will assist in tracking and understanding the patterns and determinants of the global spread of SARS-CoV-2.

microbiology↗

bioRxiv2020

Identification of Photorhabdus symbionts by MALDI-TOF mass spectrometry

Species of the bacterial genus Photorhabus live in a symbiotic relationship with Heterorhabditis entomopathogenic nematodes. Besides their use as biological control agents against agricultural pests, some Photorhabdus species are also a source of natural products and are of medical interest due to their ability to cause tissue infections and subcutaneous lesions in humans. Given the diversity of Photorhabdus species, rapid and reliable methods to resolve this genus to the species level are needed. In this study, we evaluated the potential of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for the identification of Photorhabdus species. To this end, we established a collection of 54 isolates consisting of type strains and multiple field strains that belong to each of the validly described species and subspecies of this genus. Reference spectra for the strains were generated and used to complement a currently available database. The extended reference database was then used for identification based on the direct transfer sample preparation method and protein fingerprint of single colonies. High discrimination of distantly related species was observed. However, lower discrimination was observed with some of the most closely related species and subspecies. Our results, therefore, suggest that MALDI-TOF MS can be used to correctly identify Photorhabdus strains at the genus and species level, but has limited resolution power for closely related species and subspecies. Our study demonstrates the suitability and limitations of MALDI-TOF-based identification methods for the assessment of the taxonomical position and identification of Photorhabdus isolates. Impact StatementSpecies of the bacterial genus Photorhabus live in close association with soil-born entomopathogenic nematodes. Under natural conditions, these bacteria are often observed infecting soil-associated arthropods, but under certain circumstances, can also infect humans. They produce a large variety of natural products including antibiotics, insecticides, and polyketide pigments that have substantial agricultural, biotechnological and medical potential. In this study, we implement MALDI-TOF MS-based identification method to resolve the taxonomic identity of this bacterial genus, providing thereby a rapid identification tool to understanding its taxonomic diversity to boost scientific progress in medical, agricultural, and biotechnological settings.

microbiology↗