Optimizing nanopore adaptive sampling for pneumococcal serotype surveillance in complex samples using the graph-based GNASTy algorithm.

Serotype surveillance of (the pneumococcus) is critical for understanding the effectiveness of current vaccination strategies. However, existing methods for serotyping are limited in their ability to identify the co-carriage of multiple pneumococci and detect novel serotypes. To develop a scalable and portable serotyping method that overcomes these challenges, we employed Nanopore Adaptive Sampling (NAS), an on-sequencer enrichment method that selects for target DNA in real-time, for direct detection of in complex samples.

From the 100 Day Mission to 100 lines of software development: how to improve early outbreak analytics.

Since the COVID-19 pandemic, considerable advances have been made to improve epidemic preparedness by accelerating diagnostics, therapeutics, and vaccine development. However, we argue that it is crucial to make equivalent efforts in the field of outbreak analytics to help ensure reliable, evidence-based decision making. To explore the challenges and key priorities in the field of outbreak analytics, the Epiverse-TRACE initiative brought together a multidisciplinary group of experts, including field epidemiologists, data scientists, academics, and software engineers from public health institutions across multiple countries.

Seamless, rapid, and accurate analyses of outbreak genomic data using split -mer analysis.

Sequence variation observed in populations of pathogens can be used for important public health and evolutionary genomic analyses, especially outbreak analysis and transmission reconstruction. Identifying this variation is typically achieved by aligning sequence reads to a reference genome, but this approach is susceptible to reference biases and requires careful filtering of called genotypes. There is a need for tools that can process this growing volume of bacterial genome data, providing rapid results, but that remain simple so they can be used without highly trained bioinformaticians, expensive data analysis, and long-term storage and processing of large files.

CELEBRIMBOR: core and accessory genes from metagenomes.

Motivation: Metagenome-Assembled Genomes (MAGs) or Single-cell Amplified Genomes (SAGs) are often incomplete, with sequences missing due to errors in assembly or low coverage. This presents a particular challenge for the identification of true gene frequencies within a microbial population, as core genes missing in only a few assemblies will be mischaracterized by current pangenome approaches.

Results: Here, we present CELEBRIMBOR, a Snakemake pangenome analysis pipeline which uses a measure of genome completeness to automatically adjust the frequency threshold at which core genes are identified, enabling accurate core gene identification in MAGs and SAGs.

Comparison of gene-by-gene and genome-wide short nucleotide sequence-based approaches to define the global population structure of .

Defining the population structure of a pathogen is a key part of epidemiology, as genomically related isolates are likely to share key clinical features such as antimicrobial resistance profiles and invasiveness. Multiple different methods are currently used to cluster together closely related genomes, potentially leading to inconsistency between studies. Here, we use a global dataset of 26 306  genomes to compare four clustering methods: gene-by-gene seven-locus MLST, core genome MLST (cgMLST)-based hierarchical clustering (HierCC) assignments, life identification number (LIN) barcoding and k-mer-based PopPUNK clustering (known as GPSCs in this species).

Pangenome-spanning epistasis and coselection analysis via de Bruijn graphs.

Studies of bacterial adaptation and evolution are hampered by the difficulty of measuring traits such as virulence, drug resistance, and transmissibility in large populations. In contrast, it is now feasible to obtain high-quality complete assemblies of many bacterial genomes thanks to scalable high-accuracy long-read sequencing technologies. To exploit this opportunity, we introduce a phenotype- and alignment-free method for discovering coselected and epistatically interacting genomic variation from genome assemblies covering both core and accessory parts of genomes.

Recent approaches in computational modelling for controlling pathogen threats.

In this review, we assess the status of computational modelling of pathogens. We focus on three disparate but interlinked research areas that produce models with very different spatial and temporal scope. First, we examine antimicrobial resistance (AMR).

Inter-species gene flow drives ongoing evolution of Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis.

Streptococcus dysgalactiae subsp. equisimilis (SDSE) is an emerging cause of human infection with invasive disease incidence and clinical manifestations comparable to the closely related species, Streptococcus pyogenes. Through systematic genomic analyses of 501 disseminated SDSE strains, we demonstrate extensive overlap between the genomes of SDSE and S.

Putting everything in its place: using the INSDC compliant Pathogen Data Object Model to better structure genomic data submitted for public health applications.

Fast, efficient public health actions require well-organized and coordinated systems that can supply timely and accurate knowledge. Public databases of pathogen genomic data, such as the International Nucleotide Sequence Database Collaboration (INSDC), have become essential tools for efficient public health decisions. However, these international resources began primarily for academic purposes, rather than for surveillance or interventions.

Impact of vaccinations, boosters and lockdowns on COVID-19 waves in French Polynesia.

Estimating the impact of vaccination and non-pharmaceutical interventions on COVID-19 incidence is complicated by several factors, including successive emergence of SARS-CoV-2 variants of concern and changing population immunity from vaccination and infection. We develop an age-structured multi-strain COVID-19 transmission model and inference framework to estimate vaccination and non-pharmaceutical intervention impact accounting for these factors. We apply this framework to COVID-19 waves in French Polynesia and estimate that the vaccination programme averted 34.

fastlin: an ultra-fast program for Mycobacterium tuberculosis complex lineage typing.

Summary: Fastlin is a bioinformatics tool designed for rapid Mycobacterium tuberculosis complex (MTBC) lineage typing. It utilizes an ultra-fast alignment-free approach to detect previously identified barcode single nucleotide polymorphisms associated with specific MTBC lineages. In a comprehensive benchmarking against existing tools, fastlin demonstrated high accuracy and significantly faster running times.

The mitoepigenome responds to stress, suggesting novel mito-nuclear interactions in vertebrates.

The mitochondria are central in the cellular response to changing environmental conditions resulting from disease states, environmental exposures or normal physiological processes. Although the influences of environmental stressors upon the nuclear epigenome are well characterized, the existence and role of the mitochondrial epigenome remains contentious. Here, by quantifying the mitochondrial epigenomic response of pineal gland cells to circadian stress, we confirm the presence of extensive cytosine methylation within the mitochondrial genome.

Accurate and fast graph-based pangenome annotation and clustering with ggCaller.

Bacterial genomes differ in both gene content and sequence mutations, which underlie extensive phenotypic diversity, including variation in susceptibility to antimicrobials or vaccine-induced immunity. To identify and quantify important variants, all genes within a population must be predicted, functionally annotated, and clustered, representing the "pangenome." Despite the volume of genome data available, gene prediction and annotation are currently conducted in isolation on individual genomes, which is computationally inefficient and frequently inconsistent across genomes.

Genealogical inference and more flexible sequence clustering using iterative-PopPUNK.

Bacterial genome data are accumulating at an unprecedented speed due to the routine use of sequencing in clinical diagnoses, public health surveillance, and population genetics studies. Genealogical reconstruction is fundamental to many of these uses; however, inferring genealogy from large-scale genome data sets quickly, accurately, and flexibly is still a challenge. Here, we extend an alignment- and annotation-free method, PopPUNK, to increase its flexibility and interpretability across data sets.

Inferring the heritability of bacterial traits in the era of machine learning.

Unlabelled: Quantification of heritability is a fundamental desideratum in genetics, which allows an assessment of the contribution of additive genetic variation to the variability of a trait of interest. The traditional computational approaches for assessing the heritability of a trait have been developed in the field of quantitative genetics. However, the rise of modern population genomics with large sample sizes has led to the development of several new machine learning-based approaches to inferring heritability.

Dissemination of carbapenemase-producing in Ireland from 2012 to 2017: a retrospective genomic surveillance study.

The spread of carbapenemase-producing (CPE) is of major public health concern. The transmission dynamics of CPE in hospitals, particularly at the national level, are not well understood. Here, we describe a retrospective nationwide genomic surveillance study of CPE in Ireland between 2012 and 2017.

Novel Multilocus Sequence Typing and Global Sequence Clustering Schemes for Characterizing the Population Diversity of Streptococcus mitis.

Streptococcus mitis is a common oral commensal and an opportunistic pathogen that causes bacteremia and infective endocarditis; however, the species has received little attention compared to other pathogenic streptococcal species. Effective and easy-to-use molecular typing tools are essential for understanding bacterial population diversity and biology, but schemes specific for S. mitis are not currently available.

BlpC-mediated selfish program leads to rapid loss of Streptococcus pneumoniae clonal diversity during infection.

Successful colonization of a host requires bacterial adaptation through genetic and population changes that are incompletely defined. Using chromosomal barcoding and high-throughput sequencing, we investigate the population dynamics of Streptococcus pneumoniae during infant mouse colonization. Within 1 day post inoculation, diversity was reduced >35-fold with expansion of a single clonal lineage.

Mandrake: visualizing microbial population structure by embedding millions of genomes into a low-dimensional representation.

In less than a decade, population genomics of microbes has progressed from the effort of sequencing dozens of strains to thousands, or even tens of thousands of strains in a single study. There are now hundreds of thousands of genomes available even for a single bacterial species, and the number of genomes is expected to continue to increase at an accelerated pace given the advances in sequencing technology and widespread genomic surveillance initiatives. This explosion of data calls for innovative methods to enable rapid exploration of the structure of a population based on different data modalities, such as multiple sequence alignments, assemblies and estimates of gene content across different genomes.

Effect of childhood vaccination and antibiotic use on pneumococcal populations and genome-wide associations with disease among children in Nepal: an observational study.

Background: Pneumococcal disease is a leading cause of bacterial pneumonia and invasive bacterial disease among children globally. The reason some strains of pneumococci are more likely to cause disease, and how interventions such as vaccines and antibiotics affect pneumococcal strains is poorly understood. We aimed to identify genetic regions under selective pressure and those associated with disease through the analysis of pneumococcal whole-genome sequences.

Emergence and dissemination of antimicrobial resistance in Escherichia coli causing bloodstream infections in Norway in 2002-17: a nationwide, longitudinal, microbial population genomic study.

Background: The clonal diversity underpinning trends in multidrug resistant Escherichia coli causing bloodstream infections remains uncertain. We aimed to determine the contribution of individual clones to resistance over time, using large-scale genomics-based molecular epidemiology.

Methods: This was a longitudinal, E coli population, genomic, cohort study that sampled isolates from 22 512 E coli bloodstream infections included in the Norwegian surveillance programme on resistant microbes (NORM) from 2002 to 2017.

Intermittent fasting induces chronic changes in the hepatic gene expression of Red Jungle Fowl (Gallus gallus).

Background: Intermittent fasting (IF), the implementation of fasting periods of at least 12 consecutive hours on a daily to weekly basis, has received a lot of attention in recent years for imparting the life-prolonging and health-promoting effects of caloric restriction with no or only moderate actual restriction of caloric intake. IF is also widely practiced in the rearing of broiler breeders, the parent stock of meat-type chickens, who require strict feed restriction regimens to prevent the serious health problems associated with their intense appetites. Although intermittent fasting has been extensively used in this context to reduce feed competition and its resulting stress, the potential of IF in chickens as an alternative and complementary model to rodents has received less investigation.

Targeted control of pneumolysin production by a mobile genetic element in .

is a major human pathogen that can cause severe invasive diseases such as pneumonia, septicaemia and meningitis. Young children are at a particularly high risk, with an estimated 3-4 million cases of severe disease and between 300 000 and 500 000 deaths attributable to pneumococcal disease each year. The haemolytic toxin pneumolysin (Ply) is a primary virulence factor for this bacterium, yet despite its key role in pathogenesis, immune evasion and transmission, the regulation of Ply production is not well defined.