Biology subjects

Rey, S.

Publications and source records attributed to Rey, S..

12 recordsLinked to original sources

bioRxiv2026

End-to-end plaque counting and virus titration from laboratory plate images with deep learning

Plaque assays are the gold standard for quantifying infectious virus, yet plaque enumeration is still routinely performed manually, making virus titration labor-intensive, subjective, and difficult to standardize across analysts and laboratories. Existing automated methods primarily address individual tasks, such as plaque segmentation or counting, but do not provide an integrated workflow from plate images to biological quantification. In this paper we present Titra, an end-to-end workflow for automated cytopathic effect (CPE)-based virus titration from standard photographs of plaque assay plates. The workflow combines automatic well detection, plaque segmentation, post-processing for instance separation, plaque counting, and plaque-forming units per millilitre (PFU/mL) estimation within a single web-based platform that also enables experiment management and expert review. The approach was evaluated using images from three viral species (Mayaro virus, Coxsackievirus B3, and vaccinia virus), two plate formats (6- and 12-well), and heterogeneous image acquisition conditions, including both a newly curated dataset and the public VACVPlaque dataset. Automated plaque counts showed strong agreement with manual annotations (Pearson correlation coefficients of 0.98 for MAYV/CVB3 and 0.88 for VACV), while PFU/mL estimates closely matched manual calculations for the MAYV/CVB3 dataset (Pearson r=0.975). Comparative experiments against U-Net, StarDist, HSD-WBR, and PyPlaque demonstrated competitive segmentation and counting performance, with the proposed approach achieving the highest Dice and mAP on the public VACVPlaque dataset.

bioinformatics↗

bioRxiv2026

BIOTIA-DX RESISTANCE Achieved the Best Antimicrobial Resistance Phenotype Prediction Accuracy at CAMDA 2026

We present BIOTIA-DX RESISTANCE (BDXR), our submission to the CAMDA 2026 AMR Challenge. This work extends our CAMDA 2025 submission [1] to a new set of six species-drug pairs and adds k-mer-based feature engineering (both targeted and whole-genome) for pairs where the 2025 gene-presence base model underperforms. BDXR achieved a mean accuracy of 86.1% across the six pairs on the CAMDA 2026 test set, ranking first on four pairs, tied for first on Streptococcus pneumoniae (penicillin), and second on Campylobacter jejuni (nalidixic acid); per-pair test accuracy ranged from 69.9% (C. jejuni, nalidixic acid) to 98.8% (S. pneumoniae, penicillin). We refer the reader to our 2025 preprint [1] for the underlying workflow, dataset curation, and clinical motivation; this preprint focuses on the results and methodological changes that are new in 2026.

microbiology↗

bioRxiv2025

BIOTIA-DX RESISTANCE Achieved the Best Antimicrobial Resistance Phenotype Prediction Accuracy at CAMDA 2025

We have developed BIOTIA-DX RESISTANCE (BDXR), a bioinformatic tool for predicting antimicrobial resistance (AMR) from whole genome sequencing of microbial isolates. BDXR achieved the best accuracy of any submission to the CAMDA 2025 AMR Challenge. This years challenge focused on predicting AMR phenotype which is a more complex problem than the detection of AMR marker genes, the focus of some prior years. BDXR achieved an overall F1 score of 89% on the training set and 84.1% on the challenge test set. Accuracy varied across the 9 species and drug pairs in the competition from an F1 score of 98.4% (Campylobacter jejuni, tetracycline) to 78.5% (Pseudomonas aeruginosa, cefatzidime). BDXR is based on curation of global datasets, machine learning-based predictions from input data, and highly stringent prepreprocessing of input data and databases.

microbiology↗

bioRxiv2025

Transcriptional network analysis of PTEN protein-deficient prostate tumors reveals robust stromal reprogramming and signs of senescent paracrine communication

Among the extensive genomic alterations in prostate cancer, the genomic deletion of PTEN stands out as one of the most consistently observed and confirmed alteration. PTEN loss in prostate tumors is primarily associated with cancer cell proliferation and survival through the activation of the PI3K-AKT-mTOR signalling pathway. However, its use as a robust biomarker in the clinical practice is hampered by the complex epigenetic, transcriptional and post-translational regulation. Here, we undertook an approach that combined in situ assessment of PTEN protein with transcriptional surrogates of its activity to gain insights into the downstream functional effects of PTEN loss in primary tumors. Our extensive bioinformatic analyses, including the integration with single-cell RNA-Seq approaches in a new clinical cohort, highlighted stroma remodeling as the major cancer cell-extrinsic process associated with PTEN loss. By applying similar computational strategy on the transcriptomic data generated from primary prostate tumors of genetically engineered Pten knock-out mouse models, we validated the causal role of Pten in the stromal reaction observed in clinical specimens. Mechanistically, we provide evidence for the activation of a paracrine program that encompasses enhanced TGF-{beta} signalling and that is compatible with the secretome of PTEN-deficient senescent cancer cells. Our study provides relevant biological context to the cellular and molecular alterations unleashed upon PTEN protein loss.

cancer biology↗

bioRxiv2024

The transcriptional landscape of metastatic hormone-naive prostate cancer

Metastatic hormone-naive prostate cancer (mHNPC) is an infrequent form of this tumour type that is characterized by metastasis at the time of diagnosis and accounts for 50% of prostate cancer-related deaths. Despite the extensive characterization of localized and metastatic castration resistant prostate cancer (mCRPC), the molecular characteristics of mHNPC remain largely unexplored. Here we provide the first extensive transcriptomics characterization of mHNPC. We generated discovery and validation bulk and single-cell RNA-Seq datasets and performed integrative computational analysis in combination with experimental studies. Our results provide unprecedented evidence of the distinctive transcriptional profile of mHNPC and identify stroma remodelling as a predominant feature of these tumours. Importantly, we discover a central role for the transcription factor SOX11 in triggering a heterotypic communication that is associated to the acquisition of metastatic properties. Our study will constitute an invaluable resource for a profound understanding of mHNPC that can influence patient management.

cancer biology↗

bioRxiv2024

Subcellular visualization of the distribution of atmospheric dinitrogen fixed by Gluconacetobacter diazotrophicus bacteria in maize

Plants normally obtain the nitrogen required for growth through their roots, often after application of synthetic fertilizer to the soil, at great cost to the environment and climate. Inoculation of plant seeds with nitrogen-fixing bacteria is a promising alternative means of supplying plants the nitrogen they require in an environmentally friendly manner. When maize seeds inoculated with nitrogen-fixing Gluconacetobacter diazotrophicus (Gd) are grown for two weeks in a 15N2 air environment, nanoscale secondary ion mass spectrometry (NanoSIMS) imaging shows the distribution of fixed nitrogen with subcellular resolution, with the majority being incorporated heterogeneously into chloroplasts. Chloroplasts, as the chief energy source that drives plant growth via photosynthesis, are vital for healthy plant growth and these results help explain the observations of enhanced growth rates in plants containing this nitrogen fixing bacteria. The methodology provides a template upon which more powerful, correlative studies combining genomic and/or spatial transcriptomic methods may be based.

plant biology↗

bioRxiv2024

Cell wall digestibility outperforms ear in maintaining digestibility even under severe combined water and heat stress

CONTEXT OR PROBLEMForage maize is a central pillar of dairy cow feeding in France, directly influencing milk production. Drought significantly affects both maize yield and digestibility, which are both key parameters required for hybrid registration purposes. OBJECTIVE OR RESEARCH QUESTIONResearch on maize inbred lines has revealed droughts notable effect on dry matter and cell wall digestibilities due to changes in cell wall composition, directly impacting forage quality. No such studies have been performed on forage maize hybrids however, which are the main seed type used in the agricultural sector. In this paper, we aimed to understand the impact of water and heat stress on forage maize digestibility, and to uncover the factors controlling it. METHODSWe grew a range of modern forage maize hybrids for two years under four different controlled water stress modalities. These plants were agronomically, biochemically and histologically assayed, allowing us to perform a multiscale analysis to determine the traits responsible for variations in digestibility. RESULTSBy establishing a comprehensive heat and water stress index, we classified the environmental conditions. We demonstrated that under severe stress, ear production decreases significantly, but dry matter digestibility can be maintained through increased cell wall digestibility. This boost in cell wall digestibility was due to a reduction in p-hydroxycinnamic acid content and changes in lignin distribution, while lignin content and structure remained stable. The significant impact of lignin distribution on cell wall digestibility increased with the severity of the stress, reaching an extreme threshold where biochemical parameters solely account for digestibility variations. CONCLUSION AND IMPLICATIONSTo improve maize digestibility, it will be necessary to better understand how the reduction in carbon flux under stress affects p-hydroxycinnamic acid levels without greatly impacting lignin content. Finally, our work suggests that the inclusion of moderate stress conditions in future maize breeding programs will be necessary to better adapt forage maize hybrids to climate change.

plant biology↗

bioRxiv2023

Glial-dependent clustering of voltage-gated ion channels in Drosophila precedes myelin formation

Neuronal information conductance depends on transmission of action potentials. The conductance of action potentials is based on three physical parameters: The axial resistance of the axon, the axonal insulation by glial membranes, and the positioning of voltage-gated ion channels. In vertebrates, myelin and channel clustering allow fast saltatory conductance. Here we show that in Drosophila melanogaster voltage-gated sodium and potassium channels, Para and Shal, co-localize and cluster in an area of motor axons resembling the axon initial segment. Para but not Shal localization depends on peripheral glia. In larvae, relatively low levels of Para channels are needed to allow proper signal transduction and nerves are simply wrapped by glial cells. In adults, the concentration of Para at the axon initial segment increases. Concomitantly, these axon domains are covered by a mesh of glial processes forming a lacunar structure that serves as an ion reservoir. Directly flanking the voltage-gated ion channel rich axon segment, the lacunar structures collapse forming a myelin-like insulation. Thus, Drosophila development may reflect the evolution of myelin which forms in response to increased levels of clustered voltage-gated ion channels. One-Sentence SummaryEvolution of saltatory conductance is mirrored in fly development where glia dependent clustering of voltage-gated ion channels precedes myelination.

neuroscience↗

bioRxiv2022

Daily administration of low-dose daunorubicin or doxorubicin inhibits hypoxia-inducible factor 1 and tumor vascularization

Using a hypoxia-inducible factor 1 (HIF-1)-dependent luciferase reporter in Hep3B human hepatocellular carcinoma cells, we screened over 3,000 drugs that have been used in clinical trials and identified multiple anthracyclines as inhibitors of HIF-1 activity. Anthracyclines interfered with the ability of HIF-1 to bind to DNA. Daily injection of tumor-bearing mice with anthracyclines at low dose inhibited expression of the luciferase reporter and HIF-1 target genes that encode vascular endothelial growth factor A (VEGFA; ligand of VEGFR2), stromal-derived factor 1 (SDF-1; ligand of CXCR4), and stem cell factor (SCF; ligand of CD117) in tumor tissue. Increased numbers of circulating CXCR4+/Sca1+, VEGFR2+/CD34+, and VEGFR2+/CD117+ cells were demonstrated in immunodeficient mice bearing prostate cancer xenografts but not in tumor-bearing mice treated with anthracyclines, which also significantly inhibited angiogenesis in tumor tissue. Our findings indicate that HIF-1 inhibition underlies the anti-angiogenic effect associated with daunorubicin or doxorubicin metronomic therapy and suggest that these drugs may be particularly effective in patients with high levels of HIF-1 in their diagnostic tumor biopsy.

cancer biology↗

bioRxiv2021

Drosophila beta-Heavy-Spectrin is required in polarized ensheathing glia that forma diffusion-barrier around the neuropil

In the central nervous system (CNS), functional tasks are often allocated to distinct compartments. This is also evident in the insect CNS where synapses and dendrites are clustered in distinct neuropil regions. The neuropil is separated from neuronal cell bodies by ensheathing glia, which as we show using dye injection experiments forms an internal diffusion barrier. We find that ensheathing glial cells are polarized with a basolateral plasma membrane rich in phosphatidylinositol-(3,4,5)-triphosphate (PIP3) and the Na+/K+-ATPase Nervana2 (Nrv2) that abuts an extracellular matrix formed at neuropil-cortex interface. The apical plasma membrane is facing the neuropil and is rich in phosphatidylinositol-(4,5)-bisphosphate (PIP2) that is supported by a sub-membranous {beta}Heavy-Spectrin cytoskeleton. {beta}Heavy-spectrin mutant larvae affect ensheathing glial cell polarity with delocalized PIP2 and Nrv2 and exhibit an abnormal locomotion which is similarly shown by ensheathing glia ablated larvae. Thus, polarized glia compartmentalizes the brain and is essential for proper nervous system function.

neuroscience↗

bioRxiv2020

MAJORA: Continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance

Genomic epidemiology has become an increasingly common tool for epidemic response. Recent technological advances have made it possible to sequence genomes rapidly enough to inform outbreak response, and cheaply enough to justify dense sampling of even large epidemics. With increased availability of sequencing it is possible for agile networks of sequencing facilities to collaborate on the sequencing and analysis of epidemic genomic data. In response to the ongoing SARS-CoV-2 pandemic in the United Kingdom, the COVID-19 Genomics UK (COG-UK) consortium was formed with the aim of rapidly sequencing SARS-CoV-2 genomes as part of a national-scale genomic surveillance strategy. The network consists of universities, academic institutes, regional sequencing centres and the four UK Public Health Agencies. We describe the development and deployment of Majora, an encompassing digital infrastructure to address the challenge of collecting and integrating both genomic sequencing data and sample-associated metadata produced across the COG-UK network. The system was designed and implemented pragmatically to stand up capacity rapidly in a pandemic caused by a novel virus. This approach has underpinned the success of COG-UK, which has rapidly become the leading contributor of SARS-CoV-2 genomes to international databases and has generated over 60,000 sequences to date.

bioinformatics↗

bioRxiv2018

Poly(ADP-ribose) Polymerase-1 Hyperactivity at DNA Single-Strand Breaks Triggers Seizures and Shortened Lifespan

Defects in DNA single-strand break repair result in cerebellar ataxia which in Xrcc1Nes-Cre mice is promoted by hyperactivity of the DNA strand break sensor protein, Parp1. Here, we show that Parp1 hyperactivity extends beyond the cerebellum in Xrcc1-defective brain, resulting in lethal seizures and shortened lifespan. We demonstrate that aberrant Parp1 activation triggers seizure-like activity in Xrcc1-defective hippocampus ex vivo and aberrant presynaptic calcium signalling in isolated hippocampal neurons in vitro. Moreover, we show that these defects are prevented by Parp1 inhibition and/or deletion. Collectively, these data identify aberrant Parp1 activity at unrepaired DNA breaks as a cell-autonomous source of deregulated presynaptic calcium signalling, and highlight PARP inhibition as a possible therapeutic approach in XRCC1-mutated neurodegenerative disease. SummaryPARP1 activity and presynaptic Ca2+ signalling

neuroscience↗