Assessing the effect of model specification and prior sensitivity on Bayesian tests of temporal signal.

Our understanding of the evolution of many microbes has been revolutionised by the molecular clock, a statistical tool to infer evolutionary rates and timescales from analyses of biomolecular sequences. In all molecular clock models, evolutionary rates and times are jointly unidentifiable and 'calibration' information must therefore be used. For many organisms, sequences sampled at different time points can be employed for such calibration.

Rifaximin prophylaxis causes resistance to the last-resort antibiotic daptomycin.

Multidrug-resistant bacterial pathogens like vancomycin-resistant Enterococcus faecium (VREfm) are a critical threat to human health. Daptomycin is a last-resort antibiotic for VREfm infections with a novel mode of action, but for which resistance has been widely reported but is unexplained. Here we show that rifaximin, an unrelated antibiotic used prophylactically to prevent hepatic encephalopathy in patients with liver disease, causes cross-resistance to daptomycin in VREfm.

Longitudinal genomic analysis of Neisseria gonorrhoeae transmission dynamics in Australia.

N. gonorrhoeae, which causes the sexually transmissible infection gonorrhoea, remains a significant public health threat globally, with challenges posed by increasing transmission and antimicrobial resistance (AMR). The COVID-19 pandemic introduced exceptional circumstances into communicable disease control, impacting the transmission of gonorrhoea and other infectious diseases.

Genome-wide patterns of selection-drift variation strongly associate with organismal traits across the green plant lineage.

There are many gaps in our knowledge of how life cycle variation and organismal body architecture associate with molecular evolution. Using the diverse range of green algal body architectures and life cycle types as a test case, we hypothesize that increases in cytomorphological complexity are likely to be associated with a decrease in the effective population size, because larger-bodied organisms typically have smaller populations, resulting in increased drift. For life cycles, we expect haploid-dominant lineages to evolve under stronger selection intensity relative to diploid-dominant life cycles owing to masking of deleterious alleles in heterozygotes.

Characterising HIV-1 transmission in Victoria, Australia: a molecular epidemiological study.

Background: In Australia the incidence of HIV has declined steadily, yet sustained reduction of HIV transmission in this setting requires improved public health responses. As enhanced public health responses and prioritisation of resources may be guided by molecular epidemiological data, here we aimed to assess the applicability of these approaches in Victoria, Australia.

Methods: A comprehensive collection of HIV-1 sequences from individuals diagnosed with HIV in Victoria, Australia, between January 1st 2000 and December 31st 2020 were deidentified and used as the basis of our assessment.

ClockstaRX: Testing Molecular Clock Hypotheses With Genomic Data.

Phylogenomic data provide valuable opportunities for studying evolutionary rates and timescales. These analyses require theoretical and statistical tools based on molecular clocks. We present ClockstaRX, a flexible platform for exploring and testing evolutionary rate signals in phylogenomic data.

Clockor2: Inferring Global and Local Strict Molecular Clocks Using Root-to-Tip Regression.

Molecular sequence data from rapidly evolving organisms are often sampled at different points in time. Sampling times can then be used for molecular clock calibration. The root-to-tip (RTT) regression is an essential tool to assess the degree to which the data behave in a clock-like fashion.

Tracing the origin of virulence.

Microbial genomes from ancient chickens uncover the drivers of pathogenicity.

Detecting Episodic Evolution through Bayesian Inference of Molecular Clock Models.

Molecular evolutionary rate variation is a key aspect of the evolution of many organisms that can be modeled using molecular clock models. For example, fixed local clocks revealed the role of episodic evolution in the emergence of SARS-CoV-2 variants of concern. Like all statistical models, however, the reliability of such inferences is contingent on an assessment of statistical evidence.

The importance of utilizing travel history metadata for informative phylogeographical inferences: a case study of early SARS-CoV-2 introductions into Australia.

Inferring the spatiotemporal spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via Bayesian phylogeography has been complicated by the overwhelming sampling bias present in the global genomic dataset. Previous work has demonstrated the utility of metadata in addressing this bias. Specifically, the inclusion of recent travel history of SARS-CoV-2-positive individuals into extended phylogeographical models has demonstrated increased accuracy of estimates, along with proposing alternative hypotheses that were not apparent using only genomic and geographical data.

Decoding the Fundamental Drivers of Phylodynamic Inference.

Despite its increasing role in the understanding of infectious disease transmission at the applied and theoretical levels, phylodynamics lacks a well-defined notion of ideal data and optimal sampling. We introduce a method to visualize and quantify the relative impact of pathogen genome sequence and sampling times-two fundamental sources of data for phylodynamics under birth-death-sampling models-to understand how each drives phylodynamic inference. Applying our method to simulated data and real-world SARS-CoV-2 and H1N1 Influenza data, we use this insight to elucidate fundamental trade-offs and guidelines for phylodynamic analyses to draw the most from sequence data.

Emergence, continuity, and evolution of Yersinia pestis throughout medieval and early modern Denmark.

The historical epidemiology of plague is controversial due to the scarcity and ambiguity of available data. A common source of debate is the extent and pattern of plague re-emergence and local continuity in Europe during the 14th-18th century CE. Despite having a uniquely long history of plague (∼5,000 years), Scandinavia is relatively underrepresented in the historical archives.

Evolutionary rate of SARS-CoV-2 increases during zoonotic infection of farmed mink.

To investigate genetic signatures of adaptation to the mink host, we characterised the evolutionary rate heterogeneity in mink-associated severe acute respiratory syndrome coronaviruses (SARS-CoV-2). In 2020, the first detected anthropozoonotic spillover event of SARS-CoV-2 occurred in mink farms throughout Europe and North America. Both spill-back of mink-associated lineages into the human population and the spread into the surrounding wildlife were reported, highlighting the potential formation of a zoonotic reservoir.

Promiscuous evolution of Group A Streptococcal M and M-like proteins.

Group A (GAS) M and M-like proteins are essential virulence factors and represent the primary epidemiological marker of this pathogen. Protein sequences encoding 1054 M, Mrp and Enn proteins, from 1668 GAS genomes, were analysed by SplitsTree4, partitioning around medoids and co-occurrence. The splits network and groups-based analysis of all M and M-like proteins revealed four large protein groupings, with multiple evolutionary histories as represented by multiple edges for most splits, leading to 'M-family-groups' (FG) of protein sequences: FG I, Mrp; FG II, M protein and Protein H; FG III, Enn; and FG IV, M protein.

Plagued by a cryptic clock: insight and issues from the global phylogeny of Yersinia pestis.

Plague has an enigmatic history as a zoonotic pathogen. This infectious disease will unexpectedly appear in human populations and disappear just as suddenly. As a result, a long-standing line of inquiry has been to estimate when and where plague appeared in the past.

Phylodynamic signatures in the emergence of community-associated MRSA.

Community-associated, methicillin-resistant (MRSA) lineages have emerged in many geographically distinct regions around the world during the past 30 y. Here, we apply consistent phylodynamic methods across multiple community-associated MRSA lineages to describe and contrast their patterns of emergence and dissemination. We generated whole-genome sequencing data for the Australian sequence type (ST) ST93-MRSA-IV from remote communities in Far North Queensland and Papua New Guinea, and the Bengal Bay ST772-MRSA-V clone from metropolitan communities in Pakistan.

Phytest: quality control for phylogenetic analyses.

Motivation: The ability to automatically conduct quality control checks on phylogenetic analyses is becoming more important with the increase in genetic sequencing and the use of real-time pipelines e.g. in the SARS-CoV-2 era.

Persistence of Rare Salmonella Typhi Genotypes Susceptible to First-Line Antibiotics in the Remote Islands of Samoa.

For decades, the remote island nation of Samoa (population ~200,000) has faced endemic typhoid fever despite improvements in water quality, sanitation, and economic development. We recently described the epidemiology of typhoid fever in Samoa from 2008 to 2019 by person, place, and time; however, the local Salmonella enterica serovar Typhi (S. Typhi) population structure, evolutionary origins, and genomic features remained unknown.

Lymphocytic Choriomeningitis Virus Infection, Australia.

During a mouse plague in early 2021, a farmer from New South Wales, Australia, sought treatment for aseptic meningitis and was subsequently diagnosed with locally acquired lymphocytic choriomeningitis virus infection. Whole-genome sequencing identified a divergent and geographically distinct lymphocytic choriomeningitis virus strain compared with other published sequences.

Epidemiological inference from pathogen genomes: A review of phylodynamic models and applications.

Phylodynamics requires an interdisciplinary understanding of phylogenetics, epidemiology, and statistical inference. It has also experienced more intense application than ever before amid the SARS-CoV-2 pandemic. In light of this, we present a review of phylodynamic models beginning with foundational models and assumptions.

Genomic epidemiology of Typhi in Central Division, Fiji, 2012 to 2016.

Background: Typhoid fever is endemic in some Pacific Island Countries including Fiji and Samoa yet genomic surveillance is not routine in such settings. Previous studies suggested imports of the global H58 clade of var Typhi ( Typhi) contribute to disease in these countries which, given the MDR potential of H58, does not auger well for treatment. The objective of the study was to define the genomic epidemiology of Typhi in Fiji.