Biology subjects

Hunt, M.

Publications and source records attributed to Hunt, M..

At least 19 recordsLinked to original sources

bioRxiv2026

Flex-It: A global standardised genotyping framework for Shigella flexneri

Shigella flexneri is the leading causative agent of shigellosis globally. The public health threat posed by S. flexneri is compounded by its emergence as a sexually transmissible infection, importance of international travel in driving dissemination, and the increasing prevalence of antimicrobial resistance (AMR). A rapid and robust computational method is needed to enhance genomic surveillance and systematically explore features of the population structure of this WHO priority pathogen, which is scalable and readily implementable across jurisdictions, particularly as vaccine development efforts are underway. Here, we present Flex-It, a genomic framework and genotyping scheme implemented in Mykrobe for S. flexneri serotypes 1-5, X & Y, compatible with previous approaches used to describe S. flexneris population structure. To develop Flex-It, we curated a retrospective dataset of 5,819 publicly available S. flexneri genomes. We characterised the global population structure for S. flexneri, exploring geographical and temporal traits, and showed the granular diversity of AMR and serotype profiles. We applied Flex-It to >13,000 genomes routinely generated by public health laboratories from Australia, the UK and the USA across a ten-year period. We found significant genotype diversity in all three locations, with the emergence of genotypes with converged resistance to all major drugs currently used for treatment. Flex-It provides an open-source, novel genotyping method that rapidly characterises S. flexneri and its ciprofloxacin resistance determinants in <1 minute from both short and long whole-genome sequencing reads. Flex-It provides the community with a standardised nomenclature to monitor the emergence and spread of S. flexneri lineages.

microbiology↗

bioRxiv2025

Mitophagy upregulates WNT5A/Ca2+ signalling to accelerate fibroblast migration and wound healing

In the event of dysregulated wound healing, hard-to-heal chronic wounds form and can place a significant burden on healthcare systems, yet gaps in knowledge surrounding the cellular and molecular processes involved have resulted in a lack of effective treatments. Here, we show that ubiquitin-independent mitophagy is upregulated in the early- and mid-wound healing stages. Additionally, enhancing mitophagy through Urolithin A treatment improved wound healing, in particular by accelerating fibroblast migration. RNAseq analysis demonstrated an upregulation of non-canonical WNT5A signalling in Urolithin A-treated fibroblasts, which was underpinned by elevated cytosolic Ca2+ buffering and CREB phosphorylation, ultimately leading to enhanced actin polymerisation and fibroblast migration. This study is thus the first to elucidate a role for mitophagy specifically in fibroblasts during wound healing; to demonstrate an important role for mitophagy in Ca2+-mediated WNT5A signalling cascades; and indicate the potential therapeutic benefits of treating non-healing wounds with mitophagy inducers such as Urolithin A.

developmental biology↗

bioRxiv2025

Mitophagy promotes metabolic reprogramming to enhance keratinocyte migration via ANGPTL4 during wound healing

Mitochondrial function and quality control is emerging as a key regulator of keratinocyte migration in both wounding and non-wound healing contexts, yet the cellular mechanisms that support this process are incompletely understood. In this study, using single-cell RNA sequencing data of human wounded tissue we identified a distinct population of migrating keratinocytes marked by the high expression of the mitophagy regulator BNIP3 during the proliferative stage of wound healing. Pharmacological induction of mitophagy with Urolithin A accelerated keratinocyte migration in vitro as well as keratinocyte function and regeneration in aged zebrafish, whilst RNA sequencing of primary human keratinocytes revealed the transcriptional upregulation of ANGPTL4 in Urolithin-A treated cells. Mechanistically, Urolithin A increased metabolic switching to a more glycolytic phenotype, leading to AKTGSK3 pathway activity and FOSL1-mediated ANGPTL4 transcription, ultimately promoting keratinocyte migration through enhanced laminin-332 production. Overall, our findings uncover a novel role for mitophagy in promoting keratinocyte migration during wound repair, and demonstrate that pharmacologically enhancing mitophagy promotes regenerative epithelial responses by enhancing FOSL1-mediated ANGPTL4 signalling through the modulation of metabolic switching. These insights significantly expand the understanding of the role of mitophagy on keratinocyte function during wound healing, linking mitophagy to metabolic adaption in keratinocytes, and provide a mechanistic basis for targeting mitophagy or downstream genes in wound healing therapies.

developmental biology↗

bioRxiv2025

Exploring the neuroimmune cellular landscape in the skin of subjects with fibromyalgia.

Fibromyalgia (FM) is a chronic disorder involving widespread pain, fatigue, and cognitive impairment. Although its pathogenesis remains uncertain, FM patients exhibit hypersensitivity, reduced intraepidermal nerve fiber density (IENFD), and more recently shown, skin immune dysregulation, possibly manifesting in cutaneous alterations in various cell populations. To characterize the cutaneous cellular landscape in FM, we assessed the sensory profile and skin cell populations across different layers within the same cohort. FM patients, compared to healthy controls (HC), showed lower pain thresholds across multiple body areas, with no differences in thermal detection. While our findings confirm previous reports for reduced PGP9.5+ IENF and increased density in mast cells in FM, we also identified novel changes, particularly in the dermis. We observed elongated thinly myelinated NF200+ fibers and reduced density in non-nerve-associated S100B+ Schwann cells in FM compared to HC. Notably, dermal CD68+ and CD163+ populations were significantly reduced in FM, accompanied by morphological changes. The CD163+ population correlated negatively and significantly against IENFD. These findings suggest that, beyond intraepidermal nerve loss, FM involves broader neuroimmune alterations in the skin, particularly within the dermis, offering new insights into its pathophysiology and establishing a foundation for future studies exploring the functional implications of these changes. SUMMARYAmong the alterations observed in patients with fibromyalgia (FM) are changes in skin innervation and differences in the density of certain immune cell populations. To better characterize FM from an integral perspective, we examined both the sensory profile and the cutaneous cellular landscape of FM patients in comparison with healthy controls (HC). FM patients exhibited lower pain thresholds across multiple body areas, with no differences in thermal detection. Consistent with previous findings, FM skin biopsies revealed reduced intraepidermal nerve fiber density and increased mast cell numbers. Beyond these known alterations, our study identified novel dermal changes, including elongated thinly myelinated NF200+ fibers, reduced density of non-nerve-associated S100B+ Schwann cells, and decreased CD68+ and CD163+ macrophage populations exhibiting morphological alterations. Notably, CD163+ cell density correlated negatively with intraepidermal nerve fiber density, highlighting potential neuroimmune mechanisms underlying the pathophysiology of FM.

immunology↗

bioRxiv2025

Rapidly and reproducibly building a comprehensive catalogueof resistance-associated variants for M. tuberculosis

BackgroundCatalogues of genetic variants associated with resistance underpin whole-genome sequencing (WGS)-based predictions of drug susceptibility in Mycobacterium tuberculosis, and are essential for molecular diagnostics and surveillance. The current gold standard catalogues are those released by the WHO but the underlying data are not fully released and they are difficult to interpret. Open and reproducible methods would help address these problems, extending the important work already done. MethodsWe have developed an automated method, catomatic, that uses a binomial test to associate informative isolates with resistance or susceptibility, and built a catalogue (catomatic-1) from the same 39,358 samples used to construct the first edition of the WHO catalogue (WHOv1). We performed a sensitivity analysis to optimise statistical and bioinformatic parameters for each drug, and benchmarked catomatic-1 against WHOv1 using an independent Validation Dataset of 14,380 isolates. FindingsBy using simpler statistics, catomatic-1 algorithmically classified 1,329 genetic variants, ranging from five for linezolid to 440 for pyrazinamide. WHOv1 included generalisable rules added by a panel of experts, increasing its predictive coverage, but at the cost of reproducibility. Despite not including such expert rules, catomatic-1 achieves comparable performance for all drugs, with sensitivities for first-line agents above 88% on the independent Validation Dataset. The automated process allowed us to efficiently explore parameter space; for instance, detecting resistant variants with low read support improved the sensitivity for all drugs. InterpretationPerformant resistance catalogues for M. tuberculosis can be built automatically using transparent and reproducible statistical methods. As more data are collected, catalogue content and performance will evolve, highlighting the need for proper versioning, machine/human readability, and open access. This approach demonstrates resistance catalogues used in surveillance and diagnostics can be rapidly and reproducibily updated. FundingThe National Institute for Health and Care Research (NIHR), Engineering and Physics Sciences Research Council (EPSRC) and ORACLE Corporation. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed and preprint servers (bioRxiv, medRxiv), and publicly available mutation catalogues for studies linking Mycobacterium tuberculosis genomic variants with drug resistance using whole-genome or targeted sequencing and phenotypic drug-susceptibility testing (pDST). Search terms combined "Mycobacterium tuberculosis", "genome sequencing", "mutation catalogue", "mutation effects", "drug resistance", and individual drug names, with no language or date restriction. We included studies providing paired, clinical genomic and pDST or MIC data, excluding purely in-silico or case-only reports. This work directly builds on methodologies and data published by five prior studies, and makes primary comparisons with the First (WHOv1) and Second (WHOv2) Editions of the WHO Catalogue of mutations in Mycobacterium tuberculosis. Added value of this studyWe developed catomatic, a transparent, reproducible tool for building catalogues of resistance- and susceptibility-associated genetic variants. Trained on the same samples used to build WHOv1 and benchmarked on an independent Validation Dataset, catomatic achieves comparable sensitivity, specificity, and definitive prediction rates to WHOv1 without expert-rule augmentation and despite using simpler statistics. It optimises parameters per drug, produces machine-readable outputs (CSV/JSON), and demonstrates that adjusting read-support thresholds can improve detection of minor resistance subpopulations. Implications of all the available evidenceCatalogues of resistance-associated variants for M. tuberculosis can be rapidly and transparently constructed. Making catalogues available in human/machine-readable formats with uncertainty estimates will improve uptake of WGS for M. tuberculosis surveillance and diagnostics; using a reproducible process permits diagnostic test manufacturers, researchers, clinical and public health laboratories to select the level of statistical support necessitated by their specific use-case, Policymakers should balance the benefits of expert rules against loss of reproducibility. Future work will expand the size of the datasets used, integrate minimum inhibitory concentration data, and establish consensus workflows for routine, transparent catalogue updates.

microbiology↗

bioRxiv2025

Complete genomes reveal the full extent of Mycobacterium tuberculosis complex diversity across evolutionary scales

Advances in short-read sequencing have enhanced our understanding of Mycobacterium tuberculosis complex (MTBC), but fail to capture its complete genomic diversity. We applied long-read sequencing to 216 isolates from the Valencia Region (Spain) and generated high-quality, complete genomes, revealing detailed insights into MTBC evolution across timescales. Complete genome comparisons increased the estimated evolutionary rate by 1.5-fold, resulting in a median of 312 (-1 to 792) additional SNPs per pairwise comparison. Multiple diversity hotspots were identified, mostly in the pe/ppe genes and driven by gene conversion. However, most PE/PPE epitopes were hyperconserved, with notable exceptions involving vaccine candidates. Incorporating previously undetected SNPs and indels improved resolution in transmission analyses. Furthermore, patient-specific reference mapping validates only 5-10% of within-host diversity detected by standard pipelines, indicating substantial overestimation in previous studies. These findings expand our view of MTBC diversity and have important implications for understanding host-pathogen interactions, epidemiology, and transmission dynamics.

genomics↗

bioRxiv2024

Typhi Mykrobe: fast and accurate lineage identification and antimicrobial resistance genotyping directly from sequence reads for the typhoid fever agent Salmonella Typhi

BackgroundTyphoid fever results from systemic infection with Salmonella enterica serovar Typhi (Typhi) and causes 10 million illnesses annually. Disease control relies on prevention (water, sanitation, and hygiene interventions or vaccination) and effective antimicrobial treatment. Antimicrobial resistant (AMR) Typhi lineages have emerged and become established in many parts of the world. Knowledge of local pathogen populations informed by genomic surveillance, including of lineages (defined by the GenoTyphi scheme) and AMR determinants, is increasingly used to inform local treatment guidelines and to inform vaccination strategy. Current tools for genotyping Typhi require multiple read alignment or assembly steps and have not been validated for analysis of data generated with Oxford Nanopore Technologies (ONT) long-read sequencing devices. Here, we introduce Typhi Mykrobe, a command line software tool for rapid genotyping of Typhi lineages, AMR determinants, and plasmid replicons direct from sequencing reads. ResultsWe validated Typhi Mykrobe lineage genotyping by comparison with the current standard read mapping-based approach and demonstrated 99.8% concordance across nearly 13,000 genomes sequenced with Illumina platforms. For the few isolates with discordant calls, we show that Typhi Mykrobe results are better supported by the evidence from raw sequence read data than the results generated using the mapping-based approach. We also demonstrate 99.9% concordance for detection of AMR determinants compared with the current standard assembly-based approach, with similar results for plasmid marker detection. Typhi Mykrobe predicts clinical resistance categorisation (S/I/R) for eight drug classes, and we show strong agreement with phenotypic categorisations generated from reference laboratory minimum inhibitory concentration (MIC) data for n=1,572 Illumina-sequenced isolates (>99% agreement within one doubling dilution). We show strong concordance (>96% for genotype and >98% for AMR and plasmid) between calls made from ONT reads and those made from Illumina reads for isolates sequenced on both platforms (n =93 genomes). Typhi Mykrobe takes less than a minute per sample and is available at https://github.com/typhoidgenomics/genotyphi. ConclusionsTyphi Mykrobe provides rapid and sensitive genotyping of Typhi genomes direct from Illumina and ONT reads, although lower accuracy was observed for R9 ONT data. It demonstrated accurate assignment of GenoTyphi lineage, detection of AMR determinants and prediction of corresponding AMR phenotypes, and identification of plasmid replicons.

microbiology↗

bioRxiv2024

Rate variation and recurrent sequence errors in pandemic-scale phylogenetics

Phylogenetic analyses of genome sequences from infectious pathogens reveal essential information regarding their evolution and transmission, as seen during the COVID-19 pandemic. Recently developed pandemic-scale phylogenetic inference methods reduce the computational demand of phylogenetic reconstruction from genomic epidemiological datasets, allowing the analysis of millions of closely related genomes. However, widespread homoplasies, due to recurrent mutations and sequence errors, cause phylogenetic uncertainty and biases. We present new algorithms and models to substantially improve the computational performance and accuracy of pandemic-scale phylogenetics. In particular, we account for, and identify, mutation rate variation and recurrent sequence errors. We reconstruct reliable and public sequence alignment and phylogenetic tree of > 2 million SARS-CoV-2 genomes encapsulating the evolutionary history and global spread of the virus up to February 2023.

bioinformatics↗

bioRxiv2024

Addressing pandemic-wide systematic errors in the SARS-CoV-2 phylogeny

The SARS-CoV-2 genome occupies a unique place in infection biology - it is the most highly sequenced genome on earth (making up over 20% of public sequencing datasets) with fine scale information on sampling date and geography, and has been subject to unprecedented intense analysis. As a result, these phylogenetic data are an incredibly valuable resource for science and public health. However, the vast majority of the data was sequenced by tiling amplicons across the full genome, with amplicon schemes that changed over the pandemic as mutations in the viral genome interacted with primer binding sites. In combination with the disparate set of genome assembly workflows and lack of consistent quality control (QC) processes, the current genomes have many systematic errors that have evolved with the virus and amplicon schemes. These errors have significant impacts on the phylogeny, and therefore over the last few years, many thousands of hours of researchers time has been spent in "eyeballing" trees, looking for artefacts, and then patching the tree. Given the huge value of this dataset, we therefore set out to reprocess the complete set of public raw sequence data in a rigorous amplicon-aware manner, and build a cleaner phylogeny. Here we provide a global tree of 4,471,579 samples, built from a consistently assembled set of high quality consensus sequences from all available public data as of June 2024, viewable at https://viridian.taxonium.org. Each genome was constructed using a novel assembly tool called Viridian (https://github.com/iqbal-lab-org/viridian), developed specifically to process amplicon sequence data, eliminating artefactual errors and mask the genome at low quality positions. We provide simulation and empirical validation of the methodology, and quantify the improvement in the phylogeny. We hope the tree, consensus sequences and Viridian will be a valuable resource for researchers.

bioinformatics↗

bioRxiv2024

AllTheBacteria - all bacterial genomes assembled, available and searchable

Public microbial genomes encode an immense record of biological diversity, evolution and molecular function, but much of this information remains difficult to reuse because raw sequencing data are not uniformly assembled, quality controlled, annotated or searchable at scale. Here we present AllTheBacteria, an open, community-built resource that transforms public bacterial short-read whole-genome sequencing reads into a uniformly processed discovery platform. The current analysed release contains 2,440,377 high-quality bacterial and archaeal genomes from 11,273 species, together with standardized taxonomic assignments, genome annotations, antimicrobial resistance calls, antiphage-defence annotations, protein structure predictions and AI-ready sequence tables. We show that this infrastructure enables applications that would otherwise be impractical, from global sequence search and outbreak contextualization to pangenome method development, antimicrobial resistance reservoir mapping and antiphage-defence ecology. As a stringent experimental demonstration, we mined 3,919,096 encrypted peptide fragments from AllTheBacteria proteomes using our deep learning model APEX 1.1, identifying 1,867 candidates with predicted antimicrobial activity. We synthesized 24 representative peptides and tested them against 20 clinically relevant bacterial strains, including antibiotic-resistant pathogens. Multiple peptides showed low-micromolar activity, membrane-responsive conformational transitions and selective envelope perturbation. A lead molecule, ATB20, reduced Acinetobacter baumannii burden in a murine skin abscess model with efficacy comparable to polymyxin B and no overt toxicity. Together, these results establish AllTheBacteria as both a foundational community resource for microbiology and a renewable engine for AI-guided antimicrobial discovery.

bioinformatics↗

bioRxiv2023

A network of CD163+ macrophages monitors enhanced permeability at the blood-dorsal root ganglion barrier

In dorsal root ganglia (DRG), macrophages reside in close proximity to sensory neurons, and their functions have largely been explored in the context of pain, nerve injury and repair. In this study, however, we discovered that the majority of macrophages in DRGs are in direct contact with the vasculature where they constantly monitor the circulation, efficiently phagocytosing proteins and macromolecules from the blood. Characterization of the DRG endothelium revealed a specialized vascular network spanning the arteriovenous axis, which gradually transformed from a barrier type endothelium in arteries to a highly permeable endothelium in veins. Macrophage phagocytosis spatially aligned with peak endothelial permeability and we identified caveolar transcytosis as a mechanism regulating endothelial permeability. Profiling of the DRG immune landscape revealed two subsets of perivascular macrophages with distinct transcriptome, turnover and function. CD163 expressing macrophages self-maintained locally, specifically participated in vasculature monitoring, displayed distinct responses during peripheral inflammation and were conserved in mouse and Man. Our work provides a molecular explanation for the permeability of the blood-DRG barrier and identifies an unappreciated role of macrophages as integral components of the DRG-neurovascular unit.

immunology↗

bioRxiv2022

Repeated evolution of bedaquiline resistance in Mycobacterium tuberculosis is driven by truncation of mmpR5

The antibiotic Bedaquiline (BDQ) is a key component of new WHO regimens for drug resistant tuberculosis (TB) but predicting BDQ resistance (BDQ-R) from genotypes remains challenging. We analysed a collection (n=505) of Mycobacterium tuberculosis from two high prevalence areas in South Africa (Cape Town and Johannesburg, 2019-2020), and found 53 independent acquisitions of 31 different mutations within the mmpR5 regulatory gene, with a particular enrichment of truncated MmpR5 in BDQ-R isolates by either frameshift or introduction of an insertion element. Truncations occurred across three M. tuberculosis lineages, impacting 66% of BDQ-R isolates. Extending our analysis to 1,961 isolates with minimum inhibitory concentrations (MICs) revealed that mmpR5-disrupted isolates had a median BDQ MIC of 0.25 mg/L, compared to the wild-type median of 0.06 mg/L. By matching mmpR5-disrupted isolates with phylogenetically close control isolates without the disruption, we were able to estimate the impact on MIC of individual mutations. In conclusion, as the MIC increase borders the ECOFF threshold for BDQ-R, we recommend the continued use of MICs and detection of MmpR5 truncations to identify modest shifts in BDQ-R.

microbiology↗

bioRxiv2022

Experience-dependent flexibility in a molecularly diverse central-to-peripheral auditory feedback system

Brainstem olivocochlear neurons (OCNs) modulate the earliest stages of auditory processing through feedback projections to the cochlea and have been shown to influence hearing and protect the ear from sound-induced damage through unclear mechanisms. Here, we used single-nucleus sequencing, anatomical reconstructions, and electrophysiology to characterize OCNs during postnatal development and after sound exposure. We identified markers for known OCN subtypes, medial (MOC) and lateral (LOC) OCNs, and show that they express distinct cohorts of physiologically relevant genes that change over development. In addition, we discovered a neuropeptide-enriched LOC subtype that produces Neuropeptide Y along with other neurotransmitters. Throughout the cochlea, both LOC subtypes extend arborizations over wide frequency domains. Moreover, LOC neuropeptide expression is strongly upregulated days after acoustic trauma, potentially providing a sustained protective signal to the cochlea. OCNs are therefore poised to have diffuse, dynamic effects on early auditory processing over timescales ranging from milliseconds to days.

neuroscience↗

bioRxiv2022

Reconstruction of visual images from mouse retinal ganglion cell spiking activity using convolutional neural networks

All visual information in mammals is encoded in the aggregate pattern of retinal ganglion cell (RGC) firing. How this information is decoded to yield percepts remains incompletely understood. We have trained convolutional neural networks with multielectrode array-recorded murine RGC responses to projected images. The trained model accurately reconstructed novel facial images solely from RGC firing data. In this model, subpopulations of cells with faster firing rates are largely sufficient for accurate reconstruction, and ON- and OFF-cells contribute complementary and overlapping information to image reconstruction. Information content for reconstruction correlates with overall firing rate, and locality of information contributing to reconstruction varies substantially across the image and retina. This model demonstrates that artificial neural networks are capable of learning multicellular sensory neural encoding, and provides a viable model for understanding visual information encoding. Significance StatementConvolutional neural networks can be trained on high-density neuronal firing data from the optic nerve to reconstruct complicated images within a defined image space.

neuroscience↗

bioRxiv2022

Landscape functional connectivity for butterflies under different scenarios of land-use, land-cover, and climate change in Australia

Pollinating invertebrates are vital to terrestrial ecosystems but are impacted by anthropogenic habitat loss/fragmentation and climate change. Conserving and improving landscape connectivity is important to offset those threats, yet its assessment for invertebrates is lacking. In this study, we evaluated the functional connectivity between protected areas in Australia for 59 butterfly species, under present conditions and different future scenarios (for 2050 and 2090) of land-use, land-cover, and climate change. Using circuit-theory analysis, we found that functional connectivity under present conditions varies widely between species, even when their estimated geographical ranges are similar. Under future scenarios, functional connectivity is predicted to decrease overall, with negative changes worsening from 2050 to 2090, although a few species are positive exceptions. We have made our results available as spatial datasets to allow comparisons with taxa from other studies and can be used to identify priority areas for conservation in terms of establishing ecological corridors or stepping-stone habitat patches. Our study highlights the importance of considering pollinating invertebrates when seeking holistic conservation and restoration of a landscapes functional connectivity, underscoring the need to expand and promote protected areas to facilitate functional connectivity under future scenarios of global change. Research DataThe habitat suitability maps and functional connectivity maps are made available as GeoTiff images via Figshare (10.6084/m9.figshare.19130078).

ecology↗

bioRxiv2022

ReadItAndKeep: rapid decontamination of SARS-CoV-2 sequencing reads

SummaryViral sequence data from clinical samples frequently contain human contamination, which must be removed prior to sharing for legal and ethical reasons. To enable host read removal for SARS-CoV-2 sequencing data on low-specification laptops, we developed ReadItAndKeep, a fast lightweight tool for Illumina and nanopore data that only keeps reads matching the SARS-CoV-2 genome. Peak RAM usage is typically below 10MB, and runtime less than one minute. We show that by excluding the polyA tail from the viral reference, ReadItAndKeep prevents bleed-through of human reads, whereas mapping to the human genome lets some reads escape. We believe our test approach (including all possible reads from the human genome, human samples from each of the 26 populations in the 1000 genomes data, and a diverse set of SARS-CoV-2 genomes) will also be useful for others. Availability and implementationReadItAndKeep is implemented in C++, released under the MIT license, and available from https://github.com/GenomePathogenAnalysisService/read-it-and-keep.

bioinformatics↗

bioRxiv2021

Minos: variant adjudication and joint genotyping of cohorts of bacterial genomes

Short-read variant calling for bacterial genomics is a mature field, and there are many widely-used software tools. Different underlying approaches (eg pileup, local or global assembly, paired-read use, haplotype use) lend each tool different strengths, especially when considering non-SNP (single nucleotide polymorphism) variation or potentially distant reference genomes. It would therefore be valuable to be able to integrate the results from multiple variant callers, using a robust statistical approach to "adjudicate" at loci where there is disagreement between callers. To this end, we present a tool, Minos, for variant adjudication by mapping reads to a genome graph of variant calls. Minos allows users to combine output from multiple variant callers without loss of precision. Minos also addresses a second problem of joint genotyping SNPs and indels in bacterial cohorts, which can also be framed as an adjudication problem. We benchmark on 62 samples from 3 species (Mycobacterium tuberculosis, Staphylococcus aureus, Klebsiella pneumoniae) and an outbreak of 385 M. tuberculosis samples. Finally, we joint genotype a large M. tuberculosis cohort (N{approx}15k) for which the rifampicin phenotype is known. We build a map of non-synonymous variants in the RRDR (rifampicin resistance determining region) of the rpoB gene and extend current knowledge relating RRDR SNPs to heterogeneity in rifampicin resistance levels. We replicate this finding in a second M. tuberculosis cohort (N{approx}13k). Minos is released under the MIT license, available at https://github.com/iqbal-lab-org/minos.

bioinformatics↗

bioRxiv2021

Predicted the impacts of climate change and extreme-weather events on the future distribution of fruit bats in Australia

AimFruit bats (Megachiroptera) are important pollinators and seed dispersers whose distribution might be affected by climate change and extreme-weather events. We assessed the potential impacts of those changes, particularly more frequent and intense heatwaves, and drought, on the future distribution of fruit bats in Australia. We also focus a case study on Tasmania, the southernmost island state of Australia, which is currently devoid of fruit bats but might serve as a future climate refugium. LocationAustralia (continental-scale study) and Tasmania. MethodsSpecies distribution modelling was used to predict the occurrence of seven species of fruit bats, using an ensemble of machine-learning algorithms. Predictors included extreme-weather events (heatwave and drought), vegetation (as a proxy for habitat) and bioclimatic variables. Predictions were made for the current-day distribution and future (2050 and 2070) scenarios using multiple emission scenarios and global circulation models. ResultsChanges in climate and extreme-weather events are forecasted to impact all fruit-bat species, with the loss and gain of suitable areas being predominantly along the periphery of a species current distribution. A higher emission scenario resulted in a higher loss of areas for Grey-headed flying fox (Pteropus poliocephalus) and Spectacled flying fox (P. conspicillatus) but a higher gain of areas for the Northern blossom bat (Macroglossus minimus). The Grey-headed flying fox (Pteropus poliocephalus) is the only study species predicted to potentially occur in Tasmania under future scenarios. Main conclusionsFruit bats are likely to respond to climate change and extreme weather by migrating to more suitable areas, including regions not historically inhabited by those species such as Tasmania--possibly leading to human-wildlife conflicts. Conservation strategies (e.g., habitat protection) should focus on areas we found to remain suitable under future scenarios, and not be limited by state-political boundaries.

ecology↗