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11 results for “within-host dynamics”
The within-host population dynamics of Mycobacterium tuberculosis vary with treatment efficacy.
<p>Data used for the publication of a paper entitled: <strong>The within-host population dynamics of <em>Mycobacterium tuberculosis</em> vary with treatment efficacy.</strong></p> <p>The data were derived from:</p> <p>1. the deep sequencing of serial sputum samples from 12 TB patients,</p> <p>2. the deep sequencing of liquid cultures derived from the expansion of individual colonies <em>in vitro</em>,</p> <p>3. <em>In </em><em>silico</em> simulations of DNA sequencing, populations and mutagenesis.</p> <p>The analytical scripts associated with the generation of the data can be found at:</p> <p>https://github.com/swisstph/TBRU_serialTB/</p> <p><strong>Paper Abstract:</strong></p> <p><strong>Background:</strong></p> <p>Combination therapy is one of the most effective tools for limiting the emergence of drug resistance. Despite the widespread adoption of combination therapy across diseases, drug resistance rates continue to rise, leading to failing treatment regimens. The mechanisms underlying treatment failure are well studied, but the processes governing successful combination therapy are poorly understood. We addressed this question by studying the population dynamics of <em>Mycobacterium tuberculosis</em> within tuberculosis patients undergoing treatment with different combinations of antibiotics.</p> <p><strong>Results:</strong></p> <p>By combining very deep whole genome sequencing (~1,000-fold genome-wide coverage) with sequential sputum sampling, we were able to detect transient genetic diversity driven by the apparently continuous turnover of minor alleles, which could serve as the source of drug-resistant bacteria. However, we report that treatment efficacy had a clear impact on the population dynamics: sufficient drug pressure bore a clear signature of purifying selection leading to apparent genetic stability. In contrast, <em>M. tuberculosis</em> populations subject to less drug pressure showed markedly different dynamics, including cases of acquisition of additional drug resistance.</p> <p><strong>Conclusions:</strong></p> <p>Our findings show that for a pathogen like <em>M. tuberculosis</em>, which is well adapted to the human host, purifying selection constrains the evolutionary trajectory to resistance in effectively treated individuals. Nonetheless, we also report a continuous turnover of minor variants, which could give rise to the emergence of drug resistance in cases of drug pressure weakening. Monitoring bacterial population dynamics could therefore provide an informative metric for assessing the efficacy of novel drug combinations.</p>
The impact of within-host coinfection interactions on between-host parasite transmission dynamics varies with spatial scale
<p>Within-host interactions among coinfecting parasites can have major consequences for individual infection risk and disease severity. However, the impact of these within-host interactions on between-host parasite transmission, and the spatial scales over which they occur, remain unknown. We developed and applied a novel spatially explicit analysis to parasite infection data from a wild wood mouse (<em>Apodemus sylvaticus</em>) population. We previously demonstrated a strong within-host negative interaction between two wood mouse gastrointestinal parasites, the nematode <em>Heligmosomoides polygyrus,</em> and the coccidian <em>Eimeria hungaryensis</em>, using drug-treatment experiments. Here, we show this negative within-host interaction can significantly alter the between-host transmission dynamics of <em>E. hungaryensis</em>, but only within spatially-restricted neighbourhoods around each host. However, for the closely related species <em>E. apionodes</em>, which experiments show does not interact strongly with <em>H. polygyrus</em>, we did not find any effect on transmission over any spatial scale. Our results demonstrate that the effects of within-host coinfection interactions can ripple out beyond each host to alter the transmission dynamics of the parasites, but only over local scales that likely reflect the spatial dimension of transmission. Hence there may be knock-on consequences of drug treatments impacting the transmission of non-target parasites, altering infection risks even for non-treated individuals in the wider neighbourhood.</p>
Host controls of within-host disease dynamics: insight from an invertebrate system
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The impact of within-host coinfection interactions on between-host parasite transmission dynamics varies with spatial scale
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Data from: Within-host stochastic emergence dynamics of immune-escape mutants
Predicting the emergence of new pathogenic strains is a key goal of evolutionary epidemiology. However, the majority of existing studies have focussed on emergence at the population level, and not within a host. In particular, the coexistence of pre-existing and mutated strains triggers a heightened immune response due to the larger total pathogen population; this feedback can smother mutated strains before they reach an ample size and establish. Here, we extend previous work for measuring emergence probabilities in non-equilibrium populations, to within-host models of acute infections. We create a mathematical model to investigate the emergence probability of a fitter strain if it mutates from a self-limiting strain that is guaranteed to go extinct in the long-term. We show that ongoing immune cell proliferation during the initial stages of infection causes a drastic reduction in the probability of emergence of mutated strains; we further outline how this effect can be accurately measured. Further analysis of the model shows that, in the short-term, mutant strains that enlarge their replication rate due to evolving an increased growth rate are more favoured than strains that suffer a lower immune-mediated death rate ('immune tolerance'), as the latter does not completely evade ongoing immune proliferation due to inter-parasitic competition. We end by discussing the model in relation to within-host evolution of human pathogens (including HIV, hepatitis C virus, and cancer), and how ongoing immune growth can affect their evolutionary dynamics.
Data from: The within-host dynamics of infection in trans-generationally primed flour beetles
Many taxa exhibit plastic immune responses initiated after primary microbial exposure that provide increased protection against disease-induced mortality and the fitness costs of infection. In several arthropod species, this protection can even be passed from parents to offspring through a phenomenon called trans-generational immune priming. Here, we first demonstrate that trans-generational priming is a repeatable phenomenon in flour beetles (Tribolium castaneum) primed and infected with Bacillus thuringiensis (Bt). We then quantify the within-host dynamics of microbes and host physiological responses in infected offspring from primed and unprimed mothers by monitoring bacterial density and using mRNA-seq to profile host gene expression, respectively, over the acute infection period. We find that priming increases inducible resistance against Bt around a critical temporal juncture where host septicaemic trajectories, and consequently survival, may be determined in unprimed individuals. Our results identify a highly differentially expressed biomarker of priming, containing an EIF4-e domain, in uninfected individuals, as well as several other candidate genes. Moreover, the induction and decay dynamics of gene expression over time suggest a metabolic shift in primed individuals. The identified bacterial and gene expression dynamics are likely to influence patterns of bacterial fitness and disease transmission in natural populations.
Data from: Within-host stochastic emergence dynamics of immune-escape mutants
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Data from: The within-host dynamics of infection in trans-generationally primed flour beetles
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The within-host dynamics of infection in trans-generationally primed beetles
GEO Series GSE95387. Tribolium castaneum. 48 samples. Type: Expression profiling by high throughput sequencing.
Data from: Expression of parasite genetic variation changes over the course of infection: implications of within-host dynamics for the evolution of virulence
How infectious disease agents interact with their host changes during the course of infection and can alter the expression of disease-related traits. Yet by measuring parasite life-history traits at one or few moments during infection, studies have overlooked the impact of variable parasite growth trajectories on disease evolution. Here we show that infection-age-specific estimates of host and parasite fitness components can reveal new insight into the evolution of parasites. We do so by characterizing the within-host dynamics over an entire infection period for five genotypes of the castrating bacterial parasite Pasteuria ramosa infecting the crustacean Daphnia magna. Our results reveal that genetic variation for parasite-induced gigantism, host castration and parasite spore loads increases with the age of infection. Driving these patterns appears to be variation in how well the parasite maintains control of host reproduction late in the infection process. We discuss the evolutionary consequences of this finding with regard to natural selection acting on different ages of infection and the mechanism underlying the maintenance of castration efficiency. Our results highlight how elucidating within-host dynamics can shed light on the selective forces that shape infection strategies and the evolution of virulence.
Data from: Expression of parasite genetic variation changes over the course of infection: implications of within-host dynamics for the evolution of virulence
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Allen Brain Atlas
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DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.