Genome entropy and network centrality contrast exploration and exploitation in evolution of foodborne pathogens.

Modelling evolution of foodborne pathogens is crucial for mitigation and prevention of outbreaks. We apply network-theoretic and information-theoretic methods to trace evolutionary pathways ofSalmonellaTyphimurium in New South Wales, Australia, by studying whole genome sequencing surveillance data over a five-year period which included several outbreaks. The study derives both undirected and directed genotype networks based on genetic proximity, and relates the network's structural property (centrality) to its functional property (prevalence). The centrality-prevalence space derived for the undirected network reveals a salient exploration-exploitation distinction across the pathogens, further quantified by the normalised Shannon entropy and the Fisher information of the corresponding shell genome. This distinction is also analysed by tracing the probability density along evolutionary paths in the centrality-prevalence space. We quantify the evolutionary pathways, and show that pathogens exploring the evolutionary search-space during the considered period begin to exploit their environment (their prevalence increases resulting in outbreaks), but eventually encounter a bottleneck formed by epidemic containment measures.

Pangenome Analysis of a Salmonella Enteritidis Population Links a Major Outbreak to a Gifsy-1-Like Prophage Containing Anti-Inflammatory Gene gogB.

A major outbreak of the globally significant Salmonella Enteritidis foodborne pathogen was identified within a large clinical data set by a program of routine WGS of clinical presentations of salmonellosis in New South Wales, Australia. Pangenome analysis helped to quantify and isolate prophage content within the accessory partition of the pangenome. A prophage similar to Gifsy-1 (henceforth GF-1L) was found to occur in all isolates of the outbreak core SNP cluster, and in three other isolates. Further analysis revealed that the GF-1L prophage carried the gogB virulence factor. These observations suggest that GF-1L may be an important marker of virulence for S. Enteritidis population screening and, that anti-inflammatory, gogB-mediated virulence currently associated with Salmonella Typhimurium may also be displayed by S. Enteritidis. IMPORTANCE We examined 5 years of genomic and epidemiological data for the significant global foodborne pathogen, Salmonella enterica. Although Salmonella enterica subspecies enterica serovar Enteritidis (S. Enteritidis) is the leading cause of salmonellosis in the USA and Europe, prior to 2018 it was not endemic in the southern states of Australia. However, in 2018 a large outbreak led to the endemicity of S. Enteritidis in New South Wales, Australia, and a unique opportunity to study this phenomenon. Using pangenome analysis we uncovered that this clone contained a Gifsy-1-like prophage harboring the known virulence factor gogB. The prophage reported has not previously been described in S. Enteritidis isolates.

Unifying pairwise interactions in complex dynamics.

Scientists have developed hundreds of techniques to measure the interactions between pairs of processes in complex systems, but these computational methods-from contemporaneous correlation coefficients to causal inference methods-define and formulate interactions differently, using distinct quantitative theories that remain largely disconnected. Here we introduce a large assembled library of 237 statistics of pairwise interactions, and assess their behavior on 1,053 multivariate time series from a wide range of real-world and model-generated systems. Our analysis highlights commonalities between disparate mathematical formulations of interactions, providing a unified picture of a rich interdisciplinary literature. Using three real-world case studies, we then show that simultaneously leveraging diverse methods can uncover those most suitable for addressing a given problem, facilitating interpretable understanding of the quantitative formulation of pairwise dependencies that drive successful performance. Our results and accompanying software enable comprehensive analysis of time-series interactions by drawing on decades of diverse methodological contributions.

A framework for considering the utility of models when facing tough decisions in public health: a guideline for policy-makers.

The COVID-19 pandemic has brought the combined disciplines of public health, infectious disease and policy modelling squarely into the spotlight. Never before have decisions regarding public health measures and their impacts been such a topic of international deliberation, from the level of individuals and communities through to global leaders. Nor have models-developed at rapid pace and often in the absence of complete information-ever been so central to the decision-making process. However, after nearly 3 years of experience with modelling, policy-makers need to be more confident about which models will be most helpful to support them when taking public health decisions, and modellers need to better understand the factors that will lead to successful model adoption and utilization. We present a three-stage framework for achieving these ends.

Simulating Transmission Scenarios of the Delta Variant of SARS-CoV-2 in Australia.

An outbreak of the Delta (B.1.617.2) variant of SARS-CoV-2 that began around mid-June 2021 in Sydney, Australia, quickly developed into a nation-wide epidemic. The ongoing epidemic is of major concern as the Delta variant is more infectious than previous variants that circulated in Australia in 2020. Using a re-calibrated agent-based model, we explored a feasible range of non-pharmaceutical interventions, including case isolation, home quarantine, school closures, and stay-at-home restrictions (i.e., "social distancing.") Our modelling indicated that the levels of reduced interactions in workplaces and across communities attained in Sydney and other parts of the nation were inadequate for controlling the outbreak. A counter-factual analysis suggested that if 70% of the population followed tight stay-at-home restrictions, then at least 45 days would have been needed for new daily cases to fall from their peak to below ten per day. Our model predicted that, under a progressive vaccination rollout, if 40-50% of the Australian population follow stay-at-home restrictions, the incidence will peak by mid-October 2021: the peak in incidence across the nation was indeed observed in mid-October. We also quantified an expected burden on the healthcare system and potential fatalities across Australia.

Genome-wide networks reveal emergence of epidemic strains of Salmonella Enteritidis.

OBJECTIVES: To enhance monitoring of high-burden foodborne pathogens, there is opportunity to combine pangenome data with network analysis. METHODS: Salmonella enterica subspecies Enterica serovar Enteritidis isolates were referred to the New South Wales (NSW) Enteric Reference Laboratory between August 2015 and December 2019 (1033 isolates in total), inclusive of a confirmed outbreak. All isolates underwent whole genome sequencing. Distances between genomes were quantified by in silico multiple-locus variable-number tandem repeat analysis (MLVA) as well as core single nucleotide polymorphisms (SNPs), which informed the construction of undirected networks. Centrality-prevalence spaces were generated from the undirected networks. Components on the undirected SNP network were considered alongside a phylogenetic tree representation. RESULTS: Outbreak isolates were identified as distinct components on the MLVA and SNP networks. The MLVA network-based centrality-prevalence space did not delineate the outbreak, whereas the outbreak was delineated in the SNP network-based centrality-prevalence space. Components on the undirected SNP network showed a high concordance to the SNP clusters based on phylogenetic analysis. CONCLUSIONS: Bacterial whole-genome data in network-based analysis can improve the resolution of population analysis. High concordance of network components and SNP clusters is promising for rapid population analyses of foodborne Salmonella spp. owing to the low overhead of network analysis.

How will mass-vaccination change COVID-19 lockdown requirements in Australia?

Background To prevent future outbreaks of COVID-19, Australia is pursuing a mass-vaccination approach in which a targeted group of the population comprising healthcare workers, aged-care residents and other individuals at increased risk of exposure will receive a highly effective priority vaccine. The rest of the population will instead have access to a less effective vaccine. Methods We apply a large-scale agent-based model of COVID-19 in Australia to investigate the possible implications of this hybrid approach to mass-vaccination. The model is calibrated to recent epidemiological and demographic data available in Australia, and accounts for several components of vaccine efficacy. Findings Within a feasible range of vaccine efficacy values, our model supports the assertion that complete herd immunity due to vaccination is not likely in the Australian context. For realistic scenarios in which herd immunity is not achieved, we simulate the effects of mass-vaccination on epidemic growth rate, and investigate the requirements of lockdown measures applied to curb subsequent outbreaks. In our simulations, Australia's vaccination strategy can feasibly reduce required lockdown intensity and initial epidemic growth rate by 43% and 52%, respectively. The severity of epidemics, as measured by the peak number of daily new cases, decreases by up to two orders of magnitude under plausible mass-vaccination and lockdown strategies. Interpretation The study presents a strong argument for a large-scale vaccination campaign in Australia, which would substantially reduce both the intensity of future outbreaks and the stringency of non-pharmaceutical interventions required for their suppression. Funding Australian Research Council; National Health and Medical Research Council.

Modelling transmission and control of the COVID-19 pandemic in Australia.

There is a continuing debate on relative benefits of various mitigation and suppression strategies aimed to control the spread of COVID-19. Here we report the results of agent-based modelling using a fine-grained computational simulation of the ongoing COVID-19 pandemic in Australia. This model is calibrated to match key characteristics of COVID-19 transmission. An important calibration outcome is the age-dependent fraction of symptomatic cases, with this fraction for children found to be one-fifth of such fraction for adults. We apply the model to compare several intervention strategies, including restrictions on international air travel, case isolation, home quarantine, social distancing with varying levels of compliance, and school closures. School closures are not found to bring decisive benefits unless coupled with high level of social distancing compliance. We report several trade-offs, and an important transition across the levels of social distancing compliance, in the range between 70% and 80% levels, with compliance at the 90% level found to control the disease within 13-14 weeks, when coupled with effective case isolation and international travel restrictions.

Inferring evolutionary pathways and directed genotype networks of foodborne pathogens.

Modelling the emergence of foodborne pathogens is a crucial step in the prediction and prevention of disease outbreaks. Unfortunately, the mechanisms that drive the evolution of such continuously adapting pathogens remain poorly understood. Here, we combine molecular genotyping with network science and Bayesian inference to infer directed genotype networks-and trace the emergence and evolutionary paths-of Salmonella Typhimurium (STM) from nine years of Australian disease surveillance data. We construct networks where nodes represent STM strains and directed edges represent evolutionary steps, presenting evidence that the structural (i.e., network-based) features are relevant to understanding the functional (i.e., fitness-based) progression of co-evolving STM strains. This is argued by showing that outbreak severity, i.e., prevalence, correlates to: (i) the network path length to the most prevalent node (r = -0.613, N = 690); and (ii) the network connected-component size (r = 0.739). Moreover, we uncover distinct exploration-exploitation pathways in the genetic space of STM, including a strong evolutionary drive through a transition region. This is examined via the 6,897 distinct evolutionary paths in the directed network, where we observe a dominant 66% of these paths decrease in network centrality, whilst increasing in prevalence. Furthermore, 72.4% of all paths originate in the transition region, with 64% of those following the dominant direction. Further, we find that the length of an evolutionary path strongly correlates to its increase in prevalence (r = 0.497). Combined, these findings indicate that longer evolutionary paths result in genetically rare and virulent strains, which mostly evolve from a single transition point. Our results not only validate our widely-applicable approach for inferring directed genotype networks from data, but also provide a unique insight into the elusive functional and structural drivers of STM bacteria.

Network properties of salmonella epidemics.

We examine non-typhoidal Salmonella (S. Typhimurium or STM) epidemics as complex systems, driven by evolution and interactions of diverse microbial strains, and focus on emergence of successful strains. Our findings challenge the established view that seasonal epidemics are associated with random sets of co-circulating STM genotypes. We use high-resolution molecular genotyping data comprising 17,107 STM isolates representing nine consecutive seasonal epidemics in Australia, genotyped by multiple-locus variable-number tandem-repeats analysis (MLVA). From these data, we infer weighted undirected networks based on distances between the MLVA profiles, depicting epidemics as networks of individual bacterial strains. The network analysis demonstrated dichotomy in STM populations which split into two distinct genetic branches, with markedly different prevalences. This distinction revealed the emergence of dominant STM strains defined by their local network topological properties, such as centrality, while correlating the development of new epidemics with global network features, such as small-world propensity.

Urbanization affects peak timing, prevalence, and bimodality of influenza pandemics in Australia: Results of a census-calibrated model.

We examine salient trends of influenza pandemics in Australia, a rapidly urbanizing nation. To do so, we implement state-of-the-art influenza transmission and progression models within a large-scale stochastic computer simulation, generated using comprehensive Australian census datasets from 2006, 2011, and 2016. Our results offer a simulation-based investigation of a population's sensitivity to pandemics across multiple historical time points and highlight three notable trends in pandemic patterns over the years: increased peak prevalence, faster spreading rates, and decreasing spatiotemporal bimodality. We attribute these pandemic trends to increases in two key quantities indicative of urbanization: the population fraction residing in major cities and international air traffic. In addition, we identify features of the pandemic's geographic spread that we attribute to changes in the commuter mobility network. The generic nature of our model and the ubiquity of urbanization trends around the world make it likely for our results to be applicable in other rapidly urbanizing nations.

Robotic ecology: Tracking small dynamic animals with an autonomous aerial vehicle.

Understanding animal movements that underpin ecosystem processes is fundamental to ecology. Recent advances in animal tags have increased the ability to remotely locate larger species; however, this technology is not suitable for up to 70% of the world's bird and mammal species. The most widespread technique for tracking small animals is to manually locate low-power radio transmitters from the ground with handheld equipment. Despite this labor-intensive technique being used for decades, efforts to reduce or automate this process have had limited success. Here, we present an approach for tracking small radio-tagged animals by using an autonomous and lightweight aerial robot. We present experimental results where we used the robot to locate critically endangered swift parrots (Lathamus discolor) within their winter range. The system combines a miniaturized sensor with newly developed estimation algorithms to yield unambiguous bearing- and range-based measurements with associated measures of uncertainty. We incorporated these measurements into Bayesian data fusion and information-based planning algorithms to control the position of the robot as it collected data. We report estimated positions that lie within about 50 meters of the true positions of the birds on average, which are sufficiently accurate for recapture or observation. Further, in comparison with experienced human trackers from locations where the signal was detectable, the robot produced a correct estimate as fast or faster than the human. These results provide validation of robotic systems for wildlife radio telemetry and suggest a way for widespread use as human-assistive or autonomous devices.

Minimising the Kullback-Leibler Divergence for Model Selection in Distributed Nonlinear Systems.

The Kullback-Leibler (KL) divergence is a fundamental measure of information geometry that is used in a variety of contexts in artificial intelligence. We show that, when system dynamics are given by distributed nonlinear systems, this measure can be decomposed as a function of two information-theoretic measures, transfer entropy and stochastic interaction. More specifically, these measures are applicable when selecting a candidate model for a distributed system, where individual subsystems are coupled via latent variables and observed through a filter. We represent this model as a directed acyclic graph (DAG) that characterises the unidirectional coupling between subsystems. Standard approaches to structure learning are not applicable in this framework due to the hidden variables; however, we can exploit the properties of certain dynamical systems to formulate exact methods based on differential topology. We approach the problem by using reconstruction theorems to derive an analytical expression for the KL divergence of a candidate DAG from the observed dataset. Using this result, we present a scoring function based on transfer entropy to be used as a subroutine in a structure learning algorithm. We then demonstrate its use in recovering the structure of coupled Lorenz and Rössler systems.

Quantifying Long-Range Interactions and Coherent Structure in Multi-Agent Dynamics.

We develop and apply several novel methods quantifying dynamic multi-agent team interactions. These interactions are detected information-theoretically and captured in two ways: via (i) directed networks (interaction diagrams) representing significant coupled dynamics between pairs of agents, and (ii) state-space plots (coherence diagrams) showing coherent structures in Shannon information dynamics. This model-free analysis relates, on the one hand, the information transfer to responsiveness of the agents and the team, and, on the other hand, the information storage within the team to the team's rigidity and lack of tactical flexibility. The resultant interaction and coherence diagrams reveal implicit interactions, across teams, that may be spatially long-range. The analysis was verified with a statistically significant number of experiments (using simulated football games, produced during RoboCup 2D Simulation League matches), identifying the zones of the most intense competition, the extent and types of interactions, and the correlation between the strength of specific interactions and the results of the matches.