Biology subjects

Talbot, S.

Publications and source records attributed to Talbot, S..

13 recordsLinked to original sources

bioRxiv2026

Accurate ab initio gene prediction in eukaryotes with Tiberius in multiple clades

BackgroundEukaryotic genome annotation is currently bottlenecked by limitations in the generality, scalability or accuracy of computational methods and fewer than 20% of the genomes available at NCBI Datasets have associated gene annotations. Evidence-based pipelines such as BRAKER3 achieve high accuracy but require substantial extrinsic evidence and compute. Deep learning approaches have recently achieved large improvements in ab initio gene prediction accuracy. The end-to-end deep learning gene predictor Tiberius approaches the accuracy of evidence-based annotation on mammalian genomes without using any extrinsic evidence, but its published models were trained on mammals only, limiting its applicability across eukaryotes. ResultsWe extend Tiberius beyond mammals by training lineage-specific models for Mesan-giospermae, Fungi, Vertebrata, Insecta, Chlorophyta and Bacillariophyta, making the tool applicable to 92% of currently available eukaryotic assemblies. Across a benchmark of 33 species, Tiberius achieved higher exon-, transcript- and gene-level accuracy than the other evaluated ab initio methods, Helixer and ANNEVO, improving gene-level F1 score by 12-37 percentage points over Helixer and by 10-22 percentage points over ANNEVO, while also having the fastest runtimes overall. Compared with BRAKER3, which incorporates RNA-Seq and protein evidence, Tiberius approaches state-of-the-art accuracy in Mesangiospermae, Fungi, Bacillariophyta and Chlorophyta, while being on average 80 times faster when using a GPU. A reimplementation of the Tiberius backend reduced runtime by 31% compared to the previous implementation. Tiberius and its models are also available through a web server, which allows annotation of submitted assemblies without local resources. Furthermore, the Vertebrata model has been applied to annotate 2,948 vertebrate assemblies totalling nearly 6 trillion base pairs. ConclusionsTiberius is transferable well beyond Mammalia and reaches accuracy close to evidence-based annotation in several clades at a small fraction of the compute cost. This makes it a practical choice for highly accurate large-scale genome annotation, particularly when extrinsic evidence is unavailable or annotation throughput is limiting. Availability and implementationCode: https://github.com/Gaius-Augustus/Tiberius, web server: https://bioinf.uni-greifswald.de/tiberius.

bioinformatics↗

bioRxiv2026

Grapevine Red Blotch Virus Induces Haplotype-specific Genetic and Epigenetic Responses

Haplotype-resolved genomes provide a powerful framework for uncovering allele-specific regulatory mechanisms obscured in collapsed diploid references. Despite growing evidence of cultivar- and clone-dependent variation in disease severity caused by Grapevine Red Blotch Virus (GRBV), the contribution of haplotype-specific transcriptional and epigenetic regulation to host-virus interactions remains poorly understood. Here, we integrate a haplotype-resolved grapevine genome with time-resolved transcriptomic and whole-genome bisulfite sequencing to dissect allele-specific regulatory responses to GRBV infection. Allele-aware RNA-seq analysis revealed extensive haplotype-dependent transcriptional remodeling, with both shared and divergent temporal expression programs across infection stages. Soft clustering and weighted gene co-expression network analysis (WGCNA) identified haplotype-specific co-expression modules and regulatory hubs, uncovering asymmetric network organization and distinct antiviral strategies between parental haplotypes. Notably, chloroplast-associated defense networks emerged as conserved but highly infection-sensitive modules, exhibiting haplotype-dependent recovery or sustained disruption during infection. Methylome profiling demonstrated that GRBV infection induces pronounced haplotype-specific epigenetic reprogramming, with differential DNA methylation concentrated in promoter-proximal and transposable element-associated regions. Together, our results demonstrate that haplotype-resolved, multi-omic analyses reveal regulatory complexity and divergent antiviral strategies that are hidden by collapsed-genome approaches. This work provides new mechanistic insight into grapevine-virus interactions and lays a foundation for leveraging allelic variation to improve disease resilience in clonally propagated crops.

plant biology↗

bioRxiv2024

TUMOR-INFILTRATING NOCICEPTOR NEURONS PROMOTE IMMUNOSUPPRESSION

Nociceptor neurons impact tumor immunity. Removing nociceptor neurons reduced myeloid-derived suppressor cell (MDSCs) tumor infiltration in mouse models of head and neck carcinoma and melanoma. Carcinoma-released small extracellular vesicles (sEVs) attract nociceptive nerves to tumors. sEV-deficient tumors fail to develop in mice lacking nociceptor neurons. Exposure of dorsal root ganglia (DRG) neurons to cancer sEVs elevated expression of Substance P, IL-6 and injury-related neuronal markers while treatment with cancer sEVs and cytotoxic CD8 T-cells induced an immunosuppressive state (increased exhaustion ligands and cytokines). Cancer patient sEVs enhanced DRG responses to capsaicin, indicating increased nociceptor sensitivity. Conditioned media from DRG and cancer cell co-cultures promoted expression of MDSC markers in primary bone marrow cells while DRG conditioned media together with cancer sEVs induced checkpoint expression on T-cells. Our findings indicate that nociceptor neurons facilitate CD8+ T cell exhaustion and enhance MDSC infiltration. Targeting nociceptor-released IL-6 emerges as a novel strategy to disrupt harmful neuro-immune interactions in cancer and enhance anti-tumor immunity.

cancer biology↗

bioRxiv2024

Nociceptor Neurons Control Pollution-Mediated Neutrophilic Asthma

The immune and sensory nervous systems, having evolved in parallel, communicate through shared receptors and transmitters to maintain homeostasis and respond to both external and internal disruptions. Although neural responses often confer protective benefits, they can also exacerbate inflammation during allergic reactions such as asthma. In our study, we modeled pollution-exacerbated asthma by exposing mice to ambient PM2.5 particles alongside ovalbumin. Compared to exposure to ovalbumin alone, this co-exposure significantly increased the numbers of neutrophils and {gamma}{delta} T cells in bronchoalveolar lavage fluid. We found that silencing nociceptor neurons at the peak of inflammation using intranasal QX-314 or ablating TRPV1-expressing neurons reduced lung neutrophil accumulation. Live in vivo intravital imaging confirmed that neuronal ablation reduced neutrophil numbers and increased their net displacement capacity. In neurons isolated from mice with pollution-exacerbated asthma, the chemical-sensing TRPA1 channel exhibited heightened sensitivity to its cognate ligand. Elevated levels of artemin were detected in the bronchoalveolar lavage fluid of pollution-exposed mice but returned to baseline in mice with ablated nociceptor neurons. Alveolar macrophages expressing the pollution-sensing aryl hydrocarbon receptor were identified as a putative source of artemin following exposure to PM2.5. This molecule enhanced TRPA1 responsiveness and, in turn, drove nociceptor-mediated neutrophil recruitment, revealing a novel mechanism by which lung-innervating neurons respond to air pollution in the context of allergy. Overall, our findings suggest that targeting artemin-driven pathways could provide a therapeutic strategy for controlling neutrophilic airway inflammation in asthma, a clinical condition typically refractory to treatment.

immunology↗

bioRxiv2024

BASOPHILS ACTIVATE PRURICEPTOR-LIKE VAGAL SENSORY NEURONS.

Vagal sensory neurons convey sensations from internal organs along the vagus nerve to the brainstem. Pruriceptors are a subtype of neurons that transmit itch and induce pruritus. Despite extensive research on the molecular mechanisms of itch, studies focusing on pruriceptors in the vagal ganglia still need to be explored. In this study, we characterized vagal pruriceptor neurons by their responsiveness to pruritogens such as lysophosphatidic acid, {beta}-alanine, chloroquine, and the cytokine oncostatin M. We discovered that lung-resident basophils produce oncostatin M and that its release can be induced by engagement of Fc{varepsilon}RI. Oncostatin M then sensitizes multiple populations of vagal sensory neurons, including Tac1+ and MrgprA3+ neurons in the jugular ganglia. Finally, we observed an increase in oncostatin M release in mice sensitized to the house dust mite Dermatophagoides pteronyssinus or to the fungal allergen Alternaria alternata, highlighting a novel mechanism through which basophils and vagal sensory neurons may communicate during type I hypersensitivity diseases such as allergic asthma.

neuroscience↗

bioRxiv2024

10x GENOMICS GENE EXPRESSION FLEX IS A POWERFUL TOOL FOR SINGLE-CELL TRANSCRIPTOMICS OF XENOGRAFT MODELS

The 10x Genomics Gene Expression Flex protocol allows profiling of fixed or frozen material, greatly simplifying the logistics of sample collection, storage and transfer prior to single -cell sequencing. The method makes single-cell transcriptomics possible for existing fresh-frozen or FFPE tissue samples, but also facilitates the logistics of the sampling process, allowing instant preservation of samples. The technology relies on species-specific probes available for human and mouse. Nevertheless, processing of patient-derived (PDX) or cell line (CDX) xenografts, which contain mixed human and mouse cells, is currently not supported by this protocol due to the high degree of homology between the probe sets. Here we show that it is feasible to simultaneously profile populations containing both human and mouse cells by mixing the transcriptome probe sets of both species. Cellranger outputs a count table for each of the species allowing evaluation of the performance of the different probe sets. Cross-reactive probes are greatly outperformed by the specific probe hybridizations leading to a clear difference in the recovery of UMIs and unique genes per cell. Furthermore, we developed a pipeline that removes cross-reactive signal from the data and provides species-specific count tables for further downstream analysis. Hence, the 10x Genomics Gene Expression Flex protocol can be used to process xenograft samples without the need for separation of human and mouse cells by flow sorting and allows analysis of the human and mouse single-cell transcriptome from each sample. We anticipate it will be increasingly used for single-cell sequencing of cancer cell line and patient-derived xenografts, facilitating the preservation of the samples and allowing the interrogation of both the (human) xenograft and the (mouse) tumor microenvironment at single-cell resolution.

genomics↗

bioRxiv2023

Tumor-infiltrating nerves functionally alter brain circuits and modulate behavior in a male mouse model of head-and-neck cancer

Cancer patients often experience changes in mental health, prompting an exploration into whether nerves infiltrating tumors contribute to these alterations by impacting brain functions. Using a mouse model for head and neck cancer and neuronal tracing we show that tumor-infiltrating nerves connect to distinct brain areas. The activation of this neuronal circuitry altered behaviors (decreased nest-building, increased latency to eat a cookie, and reduced wheel running). Tumor-infiltrating nociceptor neurons exhibited heightened calcium activity and brain regions receiving these neural projections showed elevated Fos as well as increased calcium responses compared to non-tumor-bearing counterparts. The genetic elimination of nociceptor neurons decreased brain Fos expression and mitigated the behavioral alterations induced by the presence of the tumor. While analgesic treatment restored nesting and cookie test behaviors, it did not fully restore voluntary wheel running indicating that pain is not the exclusive driver of such behavioral shifts. Unraveling the interaction between the tumor, infiltrating nerves, and the brain is pivotal to developing targeted interventions to alleviate the mental health burdens associated with cancer. Significance StatementHead and neck cancers are infiltrated by sensory nerves which connect to a pre-existing circuit that includes areas in the brain. Neurons within this circuit are altered and mediate modifications in behavior.

cancer biology↗

bioRxiv2023

IL-13 promotes sensory-sympathetic neurons crosstalk in asthma

Nociceptor neurons play a crucial role in maintaining the bodys homeostasis by detecting and responding to potential dangers in the environment. However, this function can be detrimental during allergic reactions, since vagal nociceptors can contribute to immune cell infiltration, bronchial hypersensitivity, and mucus imbalance, in addition to causing pain and coughing. Despite this, the specific mechanisms by which nociceptors acquire pro-inflammatory characteristics during allergic reactions are not yet fully understood. In this study, we aimed to investigate the molecular profile of airway nociceptor neurons during allergic airway inflammation and identify the signals driving such reprogramming. Using retrograde tracing and lineage reporting, we identified a unique class of inflammatory vagal nociceptor neurons that exclusively innervate the airways. In the ovalbumin mouse model of airway inflammation, these neurons undergo significant reprogramming characterized by the upregulation of the NPY receptor Npy1r. A screening of cytokines and neurotrophins revealed that IL-1{beta}, IL-13 and BDNF drive part of this reprogramming. IL-13 triggered Npy1r overexpression in nociceptors via the JAK/STAT6 pathway. In parallel, sympathetic neurons and macrophages release NPY in the bronchoalveolar fluid of asthmatic mice, which limits the excitability of nociceptor neurons. Single-cell RNA sequencing of lung immune cells has revealed that a cell-specific knockout of Npy1r in nociceptor neurons in asthmatic mice leads to an increase in airway inflammation mediated by T cells. Opposite findings were observed in asthmatic mice in which nociceptor neurons were chemically ablated. In summary, allergic airway inflammation reprograms airway nociceptor neurons to acquire a pro-inflammatory phenotype, while a compensatory mechanism involving NPY1R limits nociceptor neurons activity.

neuroscience↗

bioRxiv2022

Ocean currents drive the worldwide colonization of the most widespread marine plant, eelgrass (Zostera marina)

Currents are unique drivers of oceanic phylogeography and so determine the distribution of marine coastal species, along with past glaciations and sea level changes. Here, we reconstruct the worldwide colonization history of eelgrass (Zostera marina L.), the most widely distributed marine flowering plant or seagrass from its origin in the Northwest Pacific, based on nuclear and chloroplast genomes. We identified two divergent Pacific clades with evidence for admixture along the East Pacific coast. Multiple west to east (trans-Pacific) colonization events support the key role of the North Pacific Current. Time-calibrated nuclear and chloroplast phylogenies yielded concordant estimates of the arrival of Z. marina in the Atlantic through the Canadian Arctic, suggesting that eelgrass-based ecosystems, hotspots of biodiversity and carbon sequestration, have only been present since [~]208 Kya (thousand years ago). Mediterranean populations were founded [~]53 Kya while extant distributions along western and eastern Atlantic shores coincide with the end of the Last Glacial Maximum ([~]20 Kya). The recent colonization and 5-to 7-fold lower genomic diversity of Atlantic compared to the Pacific populations raises concern and opportunity about how Atlantic eelgrass might respond to rapidly warming coastal oceans.

evolutionary biology↗

bioRxiv2020

Inhibiting cough by silencing large pore-expressing airway sensory neurons with a charged sodium channel blocker

Although multiple diseases of the respiratory system cause cough, there are few effective treatments for this common condition. We previously developed a strategy to treat pain and itch via the long-lasting inhibition of nociceptor sensory neurons with QX-314, a cationic sodium channel blocker that selectively enters only into activated nociceptors by permeating through the endogenous TRPV1 and TRPA1 large pore ion channels they express. In this study we design and characterize BW-031, a novel cationic compound with [~]6-fold greater potency than QX-314 for inhibiting sodium channels when introduced inside cells and with minimal extracellular activity. We show that inhalation of aerosolized BW-031 effectively inhibits citric acid-induced cough in an allergic inflammation guinea pig cough model. These data support the use of charged sodium channel blockers for the selective inhibition of airway sensory neurons with activated large pore channels as a novel targeted therapy for treating cough.

neuroscience↗

bioRxiv2020

Tumor-infiltrating nerves create an electro-physiologically active microenvironment and contribute to treatment resistance

Patients with densely innervated tumors do poorly as compared to those with sparsely innervated disease. Why some tumors heavily recruit nerves while others do not, remains unknown as does the functional contribution of tumor-infiltrating nerves to cancer. Moreover, while patients receive chemotherapeutic treatment, whether these drugs affect nerve recruitment has not been tested. Using a murine model of ovarian cancer, we show that tumor-infiltrating sensory nerves potentiate tumor growth, decrease survival, and contribute to treatment resistance. Furthermore, matched patient samples show significantly increased tumor innervation following chemotherapy. In vitro analysis of tumor-released extracellular vesicles (sEVs) shows they harbor neurite outgrowth activity. These data suggest that chemotherapy may alter sEV cargo, endowing it with robust nerve recruiting capacity.

cancer biology↗

bioRxiv2020

Fast Cell Parasites Detection with Neural Networks

Deep learning has dramatically improved the performance in many application areas such as image classification, object detection, speech recognition, drug discovery and etc since 2012. Where deep learning algorithms promise to discover the intricate hidden information inside the data by leveraging the large dataset, advanced model and computing power. Although deep learning techniques show medical expert level performance in a lot of medical applications, but some of the applications are still not explored or under explored due to the variation of the species. In this work, we studied the bright field based cell level Cryptosporidium and Giardia detection in the drink water with deep learning. Our experimental demonstrates that the new developed deep learning-based algorithm surpassed the handcrafted SVM based algorithm with above 97 percentage in accuracy and 700+fps in speed on embedded Jetson TX2 platform. Our research will lead to real-time and high accuracy label-free cell level Cryptosporidium and Giardia detection system in the future.

cell biology↗

bioRxiv2019

Down regulation of Hmgcr in response to Influenza A infection is independent of the IFN response in human cells

Previous studies have demonstrated that the product of the Interferon stimulated gene Ch25h, 25-Hydroxycholestrol, provides an immediate and rapid mechanism for down-regulating sterol biosynthesis, through the inhibition of Hmgcr gene expression and proteolytic degradation of HMGCR protein. Further studies provide evidence that inhibition of the sterol biosynthesis pathway by 25-HC has broad antiviral effects. In this study, Influenza A virus (IAV) replication was inhibited in cells treated with Fluvastatin or where Hmgcr expression was inhibited with an siRNA. Treatment of A549 cells with 25-HC however, resulted in a 2-fold enhancement of IAV replication despite the fact that 25-HC promotes the proteolytic degradation of HMGCR. A549 cells infected with IAV revealed a rapid loss of HMGCR protein, a reduction in Hmgcr gene expression as well as an increase in the expression of Ch25h, that were all independent of the IFN pathway. Infection of both wild-type and Ch25h-/- murine BMDMs with IAV also revealed a rapid loss of HMGCR abundance indicating that 25-HC independent mechanisms exist for promoting proteolytic degradation of HMGCR. These data for the human A549 cell line contrast with the induction of Ch25h and subsequent loss of HMGCR in murine cells that has been shown to be dependent on IFN signalling.\n\nImportanceCholesterol, a lipid, is mainly produced by the liver or obtained from everyday foods. It is an essential element of the structure of cells and is vital for maintaining the normal function of human body. In cells, cholesterol can be oxidised to oxysterols by biological catalysts, known as enzymes. Certain oxysterols have recently emerged as important elements in the immune response to micro-organisms. This project studied a key enzyme, which is a component of the cholesterol metabolism, known as 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). A set of experiments were designed and performed to study the behaviour of HMGCR following viral infections. This study lays the foundation for re-building a map of cholesterol metabolism and the immune response to viral infection. It will be useful for understanding the importance of cholesterol metabolism in infection and exploring novel antiviral strategies.

immunology↗