Biology subjects

Hanage, B.

Publications and source records attributed to Hanage, B..

4 recordsLinked to original sources

bioRxiv2024

Linkage-based ortholog refinement in bacterial pangenomes with CLARC

Bacterial genomes exhibit significant variation in gene content and sequence identity. Pangenome analyses explore this diversity by classifying genes into core and accessory clusters of orthologous groups (COGs). However, strict sequence identity cutoffs can misclassify divergent alleles as different genes, inflating accessory gene counts. CLARC (Connected Linkage and Alignment Redefinition of COGs) [https://github.com/IndraGonz/CLARC] improves pangenome analyses by condensing accessory COGs using functional annotation and linkage information. Through this approach, orthologous groups are consolidated into more practical units of selection. Analyzing 8,000+ Streptococcus pneumoniae genomes, CLARC reduced accessory gene estimates by more than 30% and improved evolutionary predictions based on accessory gene frequencies. By refining COG definitions, CLARC offers critical insights into bacterial evolution, aiding genetic studies across diverse populations.

bioinformatics↗

bioRxiv2023

Relating Ecological Diversity to Genetic Discontinuity across Bacterial Species

Bacterial genetic discontinuity, representing abrupt breaks in genomic identity among species, is crucial for grasping microbial diversity and evolution. Advances in genomic sequencing have enhanced our ability to track and characterize genetic discontinuity in bacterial populations. However, exploring systematically the degree to which bacterial diversity exists as a continuum or is sorted into discrete and readily defined species remains a challenge in microbial ecology. Here, we aimed to quantify the genetic discontinuity ({delta}) and investigate how this metric is related to ecology. We harnessed a dataset comprising 210,129 genomes to systematically explore genetic discontinuity patterns across several distantly related species, finding clear breakpoints which varied depending on the taxa in question. By delving into pangenome characteristics, we uncovered a significant association between pangenome saturation and genetic discontinuity. Closed pangenomes were associated with more pronounced breaks, exemplified by Mycobacterium tuberculosis. Additionally, through a machine learning approach, we detected key features that impact genetic discontinuity prediction. Our study enhances the understanding of bacterial genetic patterns and their ecological implications, offering insights into species boundaries for prokaryotes.

genomics↗

bioRxiv2019

Investigating within-host diversity of Mycobacterium tuberculosis reveals novel super-spreaders in the Canadian North

Tuberculosis disproportionately affects the Canadian Inuit. To address this, it is imperative we understand transmission dynamics in this population. We investigate whether deep sequencing can provide additional resolution compared to standard sequencing, using a well-characterized outbreak from the Arctic (2011-2012, 50 cases). Samples were sequenced to ~500-1000x and reads were aligned to a novel local reference genome generated with PacBio SMRT sequencing. Consensus and heterogeneous variants were identified and compared across genomes. In contrast with previous genomic analyses using ~50x depth, deep sequencing allowed us to identify a novel super-spreader who likely transmitted to up to 17 other cases during the outbreak (35% of all cases that year). It is increasingly evident that within-host diversity should be incorporated into transmission analyses; deep sequencing can facilitate accurately detection of super-spreaders and corresponding transmission clusters. This has implications not only for TB, but all genomic studies of transmission - regardless of pathogen.

genomics↗

bioRxiv2016

Speciation trajectories in recombining bacterial species

While speciation in eukaryotes is well-studied, a controversy over the nature of bacterial species due to recombination between distant strains continues. It is generally agreed that bacterial diversity can be classified into genetically and ecologically cohesive units, but what produces such variation is a topic of intensive research. Recombination may maintain coherent species of frequently recombining bacteria, but the emergence of distinct clusters within a recombining species, and the impact of habitat structure in this process are not well described, limiting our understanding of how new species are created. Here we present a model of bacterial evolution in overlapping habitat space. We show three different outcomes are possible for a pair of clusters, depending on the size of their habitat overlap: fast divergence with little interaction between the clusters, slow divergence with frequent recombination between the clusters, and stationary or near stationary population structure, where the clusters remain at an equilibrium distance for an indefinite time. We fit our model to two data sets. In Streptococcus pneumoniae, we find a genomically and ecologically distinct subset, held at a relatively constant genetic distance from the majority of the population through frequent recombination with it, while in Campylobacter jejuni, we find a minority population we predict will continue to diverge at a higher rate. This approach may predict and define speciation trajectories in multiple bacterial species.

microbiology↗