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At least 19 recordsLinked to original sources

Chemical Imaging of Retinal Pigment Epithelium in Frozen Sections of Zebrafish Larvae Using ToF-SIMS.

Variants of the SLC24A5 gene, which encodes a putative potassium-dependent sodium-calcium exchanger (NCKX5) that most likely resides in the melanosome or its precursor, affect pigmentation in both humans and zebrafish (Danio rerio). This finding suggests that genetic variations influencing human skin pigmentation alter melanosome biogenesis via ionic changes. Gaining an understanding of how changes in the ionic environment of organelles impact melanosome morphogenesis and pigmentation will require a spatially resolved way to characterize the chemical environment of melanosomes in pigmented tissue such as retinal pigment epithelium (RPE). The imaging mass spectrometry technique most suited for this type of cell and tissue analysis is time-of-flight secondary ion mass spectrometry (ToF-SIMS) because it is able to detect many biochemical species with high sensitivity and with submicron spatial resolution. Here, we describe chemical imaging of the RPE in frozen-hydrated sections of larval zebrafish using cryo-ToF-SIMS. To facilitate the data interpretation, positive and negative polarity ToF-SIMS image data were transformed into a single hyperspectral data set and analyzed using principal component analysis. The combination of a novel protocol and the use of multivariate data analysis allowed us to discover new marker ions that are attributable to leucodopachrome, a metabolite specific to the biosynthesis of eumelanin. The described methodology may be adapted for the investigation of other classes of molecules in frozen tissues from zebrafish and other organisms.

Animals

A STORM-based protocol for nanoscale imaging and quantitative analysis of protein-associated and phospholipid-associated structures in natural rubber.

Stochastic Optical Reconstruction Microscopy (STORM) enables nanoscale mapping of molecular components beyond the diffraction limit; however, its reproducible implementation in hydrophobic polymer matrices remains challenging because fluorescence-labeling specificity, fluorophore photoswitching, three-dimensional localization, chromatic registration, and quantitative image analysis must be carefully controlled. This protocol presents a standardized experimental workflow for dual-color labeling, astigmatism-based three-dimensional STORM acquisition, and quantitative analysis of protein-associated and phospholipid-associated structures in natural rubber (NR). The workflow covers sample pretreatment, Cy5 NHS ester labeling of protein-associated primary amines, DiI labeling of phospholipid-rich domains, STORM imaging-buffer preparation, three-dimensional single-molecule localization, dual-channel registration, generation of standardized xy projections, aggregate-size analysis, and projected lateral spatial correlation assessment. Reproducibility is supported by defined acquisition and localization criteria, three independent sample preparations with at least five fields of view analyzed per condition, and unlabeled, single-color, dye-only matrix, and processing-associated Cy5 controls. Mean lateral localization precisions of 11.8 ± 2.3 nm for Cy5 and 13.5 ± 2.9 nm for DiI were obtained, while two-dimensional Fourier ring correlation analysis of the xy projections yielded effective lateral image resolutions of approximately 25 and 28 nm, respectively. Image-based particle segmentation and localization-coordinate-based density-based spatial clustering of applications with noise (DBSCAN) were applied to standardized xy projections as complementary quantitative approaches. Application of the protocol to untreated, centrifuged, and protease-treated NR samples demonstrated treatment-associated changes in the detected abundance and projected size distributions of protein- and phospholipid-associated aggregates, together with a non-monotonic change in their projected lateral spatial correlation. These observations describe alterations in nanoscale organization but do not, by themselves, establish stable protein-phospholipid complex formation. Unlike previous studies that primarily demonstrated the feasibility of STORM imaging in rubber materials, the principal contribution of this work is an end-to-end, step-by-step protocol incorporating defined controls, three-dimensional localization, image-quality metrics, chromatic-registration procedures, and complementary quantitative-analysis pipelines for non-expert users. The workflow may be adaptable to other hydrophobic polymers and soft-material systems after appropriate optimization and validation.

Rubber

Integrating histology and spatial transcriptomics via multimodal transformers and contrastive representation learning for accurate gene expression prediction.

Predicting spatial gene expression from Histological images is a fundamental task in understanding tissue organization and molecular phenotypes. However, existing methods often rely on single-model representations or lack effective alignment between image and transcriptomic features. To address these limitations, we propose a unified multimodal learning framework that integrates histological imaging and spatial transcriptomics through a shared latent representation space. Specifically, histological H&E images are encoded by a ResNet50-based convolutional stem and a MobileViT Transformer backbone to extract hierarchical visual representations. Both modalities are projected into a shared latent space via linear-GELU-dropout transformation blocks, enabling cross-modal alignment through a contrastive learning objective that maximizes agreement between the corresponding image and the spot embeddings. Experimental results on the 10x Genomics Visium dataset of human liver tissue demonstrate that MViTGene achieves significantly higher prediction accuracy than existing methods across multiple gene subsets, with improvements of 20%, 33%, and 12% in predicting marker genes, highly expressed genes, and highly variable genes, respectively. The significant improvement in relevance indicates that the model can more accurately capture the true correspondence between tissue morphology and gene expression, therefore enabling more reliable biological interpretation. It provides a computational tool for high-throughput spatial gene expression prediction that balances performance and interpretability.

Humans

High-Plex Tissue Imaging with Conventional Immunofluorescence Platforms and Open-Source Software via Iterative Bleaching Extends Multiplexity (IBEX).

Iterative bleaching extends multiplexity (IBEX) is an easy-to-use, highly multiplex immunofluorescent tissue imaging method that employs widely available microscopy platforms, commercial reagents, and open-source software. In this article, we describe how to implement this method in a laboratory that has minimal experience with immunohistochemistry.

Software

Automated Classification of Lymphoma Subtypes From Histopathological Images Using a U-Net Deep Learning Model: Comparative Evaluation Study.

BACKGROUND: Accurate classification and grading of lymphoma subtypes are essential for treatment planning. Traditional diagnostic methods face challenges of subjectivity and inefficiency, highlighting the need for automated solutions based on deep learning techniques. OBJECTIVE: This study aimed to investigate the application of deep learning technology, specifically the U-Net model, in classifying and grading lymphoma subtypes to enhance diagnostic precision and efficiency. METHODS: In this study, the U-Net model was used as the primary tool for image segmentation integrated with attention mechanisms and residual networks for feature extraction and classification. A total of 620 high-quality histopathological images representing 3 major lymphoma subtypes were collected from The Cancer Genome Atlas and the Cancer Imaging Archive. All images underwent standardized preprocessing, including Gaussian filtering for noise reduction, histogram equalization, and normalization. Data augmentation techniques such as rotation, flipping, and scaling were applied to improve the model's generalization capability. The dataset was divided into training (70%), validation (15%), and test (15%) subsets. Five-fold cross-validation was used to assess model robustness. Performance was benchmarked against mainstream convolutional neural network architectures, including fully convolutional network, SegNet, and DeepLabv3+. RESULTS: The U-Net model achieved high segmentation accuracy, effectively delineating lesion regions and improving the quality of input for classification and grading. The incorporation of attention mechanisms further improved the model's ability to extract key features, whereas the residual structure of the residual network enhanced classification accuracy for complex images. In the test set (N=1250), the proposed fusion model achieved an accuracy of 92% (1150/1250), a sensitivity of 91.04% (1138/1250), a specificity of 89.04% (1113/1250), and an F1-score of 90% (1125/1250) for the classification of the 3 lymphoma subtypes, with an area under the receiver operating characteristic curve of 0.95 (95% CI 0.93-0.97). The high sensitivity and specificity of the model indicate strong clinical applicability, particularly as an assistive diagnostic tool. CONCLUSIONS: Deep learning techniques based on the U-Net architecture offer considerable advantages in the automated classification and grading of lymphoma subtypes. The proposed model significantly improved diagnostic accuracy and accelerated pathological evaluation, providing efficient and precise support for clinical decision-making. Future work may focus on enhancing model robustness through integration with advanced algorithms and validating performance across multicenter clinical datasets. The model also holds promise for deployment in digital pathology platforms and artificial intelligence-assisted diagnostic workflows, improving screening efficiency and promoting consistency in pathological classification.

Humans

An automated geometric modeling framework in GATE for the design and optimization of high-sensitivity converging-beam SPECT collimators.

Objective.The trade-off between detection sensitivity and spatial resolution is a fundamental challenge in designing organ-dedicated Single-photon emission computed tomography (SPECT) collimators. While converging-hole geometries offer a solution, their optimization is often hindered by the lack of flexible computational tools capable of modeling large-scale, non-parallel hole arrays. This study aims to develop an automated geometric modeling framework to facilitate the design and evaluation of complex converging- and diverging-hole collimators within standard Monte Carlo environments.Approach.We developed a specialized modeling framework by implementing custom C++ classes and a vector-based alignment algorithm within GATE. This platform enables automated, orientation-consistent construction of large-scale converging arrays not natively supported by standard implementations. A high-sensitivity pure cone-beam collimator (CBC) was designed using this framework. The evaluation used hot-rod, disc, and Jaszczak phantoms for physical characterization, while XCAT and dedicated brain models were employed for clinical tasks, including cardiac, brain perfusion, and DaTscan SPECT simulations.Main results.The CBC achieved a nearly fourfold sensitivity increase compared to a conventional low-energy high-resolution parallel-hole collimator at a 20 cm radius of rotation, while maintaining comparable spatial resolution. Despite a 52.3% field of view reduction, the CBC yielded a 2.2-fold noise reduction (CV: 11.7% vs 25.9%) and mitigated partial volume effects via geometric magnification. XCAT and brain phantom simulations confirmed enhanced anatomical definition and contrast recovery in cardiac, perfusion, and DaTscan tasks.Significance.This work provides an efficient computational tool for rapid design space exploration of advanced collimator geometries. The results demonstrate that the proposed CBC design offers a significant sensitivity advantage, making it highly suitable for high-performance, small-volume clinical applications such as brain and cardiac molecular imaging.

Tomography, Emission-Computed, Single-Photon

Measuring Cell Dimensions in Fission Yeast Using Machine Learning.

In fission yeast (Schizosaccharomyces pombe), cell length is a crucial indicator of cell cycle progression. Microscopy screens that examine the effect of agents or genotypes suspected of altering genomic or metabolic stability and thus cell size are crucial for studying disruptions to cell cycle dynamics. This method is based on using an automated cell segmentation algorithm to measure S. pombe cells imaged by brightfield (BF) microscopy methods. PhotoPhenosizer (PP) is a machine learning-based tool designed for automated cell measuring and dimensional analysis of morphology frequency distributions. Integration of this method into large-scale pipelines for tracking cell dimension change streamlines morphological measurements, which facilitates the examination of cellular responses to genomic and metabolic stresses. In this protocol, we use PP to observe the effect of genomic instability on cell size dynamics over a 12-day chronological lifespan assay. Our results show that relative to wild-type cells, a replication stress mutant shows larger cells during chronological aging in excess glucose media. Our results are consistent with activation of checkpoints that regulate cell morphology in response to DNA damage. This method's application highlights the relevance of its incorporation in experimental routines that require large-scale image processing and its adoption by users with routine needs in S. pombe molecular research projects.

Schizosaccharomyces

Epigenetically regulated digital signaling defines epithelial innate immunity at the tissue level.

To prevent damage to the host or its commensal microbiota, epithelial tissues must match the intensity of the immune response to the severity of a biological threat. Toll-like receptors allow epithelial cells to identify microbe associated molecular patterns. However, the mechanisms that mitigate biological noise in single cells to ensure quantitatively appropriate responses remain unclear. Here we address this question using single cell and single molecule approaches in mammary epithelial cells and primary organoids. We find that epithelial tissues respond to bacterial microbe associated molecular patterns by activating a subset of cells in an all-or-nothing (i.e. digital) manner. The maximum fraction of responsive cells is regulated by a bimodal epigenetic switch that licenses the TLR2 promoter for transcription across multiple generations. This mechanism confers a flexible memory of inflammatory events as well as unique spatio-temporal control of epithelial tissue-level immune responses. We propose that epigenetic licensing in individual cells allows for long-term, quantitative fine-tuning of population-level responses.

Animals

Automated segmentation and length measurement of metacarpal and phalangeal bones for hand radiograph evaluation.

Evaluating hand and wrist radiographs is essential in pediatric endocrinology and clinical genetics, particularly for the assessment of suspected skeletal anomalies. In this study, we present Auto-Bone-Caliper, an automated system for the segmentation and length measurement of metacarpal and phalangeal (M&P) bones, trained and evaluated on public datasets comprising both normal and dysmorphic cases. We first introduce InstanceSAM, a two-stage framework that detects and segments all 19 M&P bones in pediatric hand radiographs, achieving Dice scores of 98.7% for normal bones and 95.0% for dysmorphic bones. We further develop and evaluate three methods for bone-length estimation, identifying a k-means-based approach as the most accurate, with relative errors of 2.2% for normal bones and 4.5% for dysmorphic bones. Our automated pipeline, Auto-Bone-Caliper, integrates InstanceSAM with the k-means-based length-estimation method. To enable scale-independent downstream analyses, we derive relative bone-length measures from the automated measurements. Using these relative measures, we statistically compare measurements obtained using Auto-Bone-Caliper on an independent dataset with a healthy reference catalog of normal bone morphologies, observing a high level of agreement (Wasserstein-1 distance = 0.012). Finally, we demonstrate a potential clinical use case of Auto-Bone-Caliper by obtaining relative metacarpophalangeal pattern profiles for three genetic conditions, namely Turner syndrome, achondroplasia, and pseudohypoparathyroidism. Our results highlight the potential of the Auto-Bone-Caliper to streamline and standardize M&P length measurement, providing an objective and reproducible tool suitable for clinical application.

Humans

Foundation model based multimodal transformer framework for survival analysis in HER2 stratified breast cancer.

Objective. To improve survival prediction for HER2-positive breast cancer by integrating histopathological, molecular, and clinical data using a multimodal transformer framework.Approach. We propose a multimodal transformer framework for breast cancer survival prediction using HER2 stratified (SurvMBC), a foundation model-enhanced architecture that fuses three data modalities: whole-slide images, clinical narratives, and molecular features. Tumor microenvironment features are extracted using a pathology language and image pre-training (PLIP), clinical narratives are processed with BioBERT, and miRNA expression plus DNA methylation data are embedded using Gen2Vec. These representations are integrated through a cross-modal transformer with attention mechanisms for survival prediction.Main results. The model was evaluated on 1,095 HER2-positive breast cancer patients from The Cancer Genome Atlas. SurvMBC achieved a concordance index (C-index) of 0.857 (95% CI: 0.834, 0.880), a low integrated Brier score, and a strong inverse negative binomial log-likelihood. Risk stratification based on model outputs significantly separated high- and low-risk groups (log-rankp< 0.01) and showed strong associations with tumor stage, grade, and hormone receptor status (allp< 0.05).Significance. SurvMBC demonstrates the effectiveness of multimodal fusion in addressing tumor heterogeneity and improving prognostic accuracy. The attention-based integration enables context-aware learning of survival-relevant features across modalities, supporting individualized risk stratification and risk-adaptive treatment planning for HER2 stratified breast cancer patients.

Breast Neoplasms

A multi-scale fusion model based on multi-phase contrast-enhanced CT for predicting pancreatic cancer resectability.

Purpose.Develop a multi-scale fusion model (MSFM) based on multi-phase contrast-enhanced computed tomography (CECT) to predict pancreatic cancer (PC) resectability, thereby assisting expert decision-making.Methods.This retrospective study enrolled 280 patients with PC from four institutions, which were randomly divided into a training cohort (202 patients) and an independent test cohort (78 patients). Three-phase CECT images (arterial, venous, and delayed phases) were used for modeling. The MSFM comprises two sub-networks: (1) a multi-phase fusion network for extracting cross-phase shared fusion features, (2) a phase-specific branch network for capturing phase-specific features; and a post-fusion strategy to generate the final predictive score by integrating the shared fusion features and three groups of phase-specific features. Additionally, a human-machine fusion deep learning model (HMfDL) was constructed by fusing the predictive score of the MSFM with expert assessments.Results.In the independent test, the MSFM achieved an AUC (area under the receiver operating characteristic curve) of 0.8385 (95% CI: 0.7521-0.9249), accuracy of 84.62%, sensitivity of 72.00%, and specificity of 90.57%. This performance outperformed single-phase models (AUC range: 0.7638-0.7781), two-phase models (AUC range: 0.7826-0.7864), and ten states-of-the-art classifiers (AUC range: 0.7404-0.7796). The HMfDL further improved the performance, reaching an AUC of 0.8626 (95% CI: 0.7853-0.9400), accuracy of 91.03%, sensitivity of 80.00%, and specificity of 96.23%. Notably, the HMfDL corrected 58.82% of misdiagnosis made by experts.Conclusions. The MSFM effectively fuses multi-phase CECT to enable highly accurate predictions of PC resectability, and provides valuable support for expert decision-making through HMfDL.

Humans

Survival prediction for clear cell renal cell carcinoma based on deep multimodal synergistic survival network.

Objective.To propose a deep multimodal synergistic survival analysis framework (Deep Multimodal Synergistic Survival Network, DMSSN) to achieve accurate prognostic analysis for clear cell renal cell carcinoma (ccRCC).Methods.This study (DMSSN) utilized matched multimodal data from the Cancer Genome Atlas-KIRC database, including CT imaging data, whole slide images, copy number variation (CNV) features, and clinical data. Deep Canonical Correlation Analysis was employed to map heterogeneous modalities into a shared latent space. Contrastive learning was introduced to enhance semantic consistency across multimodal features, and a gating network was utilized for the adaptive fusion of multimodal information to achieve precise survival risk prediction for patients.Results.Experimental results demonstrated that DMSSN achieved a Concordance Index (C-index) of 0.8153 &#xb1; 0.0994, with a Log-rank testp-value of 1.6553&#xd7;10-11. DMSSN exhibited significant performance advantages over traditional statistical methods like Log-rank-Cox (0.7055 &#xb1; 0.0670) and machine learning methods such as Random Survival Forest (RSF) (0.6836 &#xb1; 0.1048). Furthermore, in comparison with similar deep learning approaches, DMSSN outperformed late fusion strategies (0.7493 &#xb1; 0.1211) and discrete-time survival models such as DeepHit (0.7655 &#xb1; 0.1041) and Nnet-surv (0.7694 &#xb1; 0.0635). Notably, DMSSN still achieved the best predictive performance when compared to the classic deep survival model DeepSurv (0.7919 &#xb1; 0.0978) and advanced state-of-the-art multimodal fusion frameworks like Context-Aware Transformer (0.7735 &#xb1; 0.0818) and Multimodal Co-Attention Transformer (0.8102 &#xb1; 0.0972). Ablation studies showed that removing any single modality led to a decline in performance, with the largest numerical decrease occurring after removing CT imaging features (C-index decreased to 0.7327), validating the complementarity of multimodal data and the pivotal role of radiomic features in prognostic assessment. Module ablation experiments further confirmed the effectiveness of the core components.Conclusion:By effectively integrating imaging, pathology, genomic, and clinical features, the DMSSN framework demonstrates superior performance and robustness in the survival prediction of ccRCC.

Carcinoma, Renal Cell

stDyer-image improves clustering analysis of spatially resolved transcriptomics and proteomics with morphological images.

MOTIVATION: Spatially resolved transcriptomics (SRT) and spatially resolved proteomics (SRP) data enable the study of gene expression and protein abundances within their precise spatial and cellular contexts in tissues. Certain SRT and SRP technologies also capture corresponding morphology images, adding another layer of valuable information. However, few existing methods developed for SRT data effectively leverage these supplementary images to enhance clustering performance. RESULTS: Here, we introduce stDyer-image, an end-to-end deep learning framework designed for clustering for SRT and SRP datasets with images. Unlike existing methods that utilize images to complement gene expression data, stDyer-image directly links image features to cluster labels. This approach draws inspiration from pathologists, who can visually identify specific cell types or tumor regions from morphological images without relying on gene expression or protein abundances. Benchmarks against state-of-the-art tools demonstrate that stDyer-image achieves superior performance in clustering. Moreover, it is capable of handling large-scale datasets across diverse technologies, making it a versatile and powerful tool for spatial omics analysis. AVAILABILITY AND IMPLEMENTATION: The source code of stDyer-image and detailed tutorials are available at https://github.com/ericcombiolab/stDyer-image.

Proteomics

Treemble: a graphical tool to generate Newick strings from phylogenetic tree images.

SUMMARY: Phylogenetic trees are ubiquitous and central to biology, but most published trees are available only as visual diagrams and not in the machine-readable Newick format. There are, thus, thousands of published trees in the scientific literature that are unavailable for follow-up analyses, comparisons, and supertree construction. Experts can easily read such diagrams, but the manual construction of a Newick string from a diagram is laborious, error-prone, and time-consuming. Previous attempts to semi-automate the reading of tree images relied on image processing techniques. These often encounter difficulties as typical published tree diagrams contain various graphical elements and annotations that overlap the branches, such as error bars on internal nodes. Here we introduce Treemble, a user-friendly desktop application for generating Newick strings from tree images. The user simply clicks to mark node locations, assisted by a deep learning-based node detection tool, and Treemble algorithmically assembles the tree from the node coordinates alone. Treemble also facilitates the automatic reading of tip name labels and can be used for both rectangular and circular trees. AVAILABILITY AND IMPLEMENTATION: Treemble is a native desktop application for macOS and Windows and is freely available, with documentation, at treemble.org. Source code is available at github.com/John-Allard/Treemble. The trained node detection model is available at huggingface.co/John-Allard/treemble-1.

Phylogeny

Striping artifact removal in VisiumHD data through nuclear counts modeling.

MOTIVATION: 10x Genomics VisiumHD enables spatial transcriptomics at 2&#x2009;&#xb5;m &#xd7; 2&#x2009;&#xb5;m resolution but exhibits slide-specific, non-periodic striping artifacts due to lane-width variability. These multiplicative row/column effects distort bin total counts and can bias downstream analyses. The state-of-the-art destriping approach is the normalization procedure used as a preprocessing step in bin2cell; it applies sequential high-quantile row- then column-wise normalization, which is asymmetric and can introduce edge effects/macro-stripes and distortions of large-scale total-count structure. RESULTS: We propose a statistical destriping approach that leverages nuclei segmentation from the co-registered H&E image. Assuming transcript abundance is constant within each nucleus, we model bin counts with a negative binomial distribution whose mean is a product of a nucleus-specific concentration and row- and column-specific stripe-factors reflecting lane-width variation. We fit all parameters in a generalized linear modeling framework with cross-validated regularization on stripe-factors and iterative dispersion estimation, and use the fitted parameters to correct the observed counts into a destriped image. On synthetic data with known ground truth, our method improves stripe-factor estimation accuracy and reduces error in corrected counts relative to bin2cell and bin2cell-derived baselines. Across four public VisiumHD slides, it consistently lowers striping intensity while substantially better preserving biological signal present in the large-scale global count structure and avoiding the artifacts introduced by other methods. AVAILABILITY AND IMPLEMENTATION: All source code and links to publicly available data used for this study are available at https://github.com/paolamalsot/destriping-GLM.

Artifacts

Informing agent-based models with spatial data using convolutional autoencoders.

MOTIVATION: Spatial computational models such as agent-based models (ABMs) offer powerful in silico tools to study tumor dynamics, yet imaging data are still rarely used to inform these models directly. RESULTS: We present an ABM optimization framework that leverages convolutional encoders to compare spatial patterns between experimental imaging data and ABM-generated outputs within a shared latent space. This quantitative comparison was used to estimate ABM parameters across three datasets, ranging from synthetic data to 3D tumoroid-T cell co-culture microscopy and histopathology images from The Cancer Genome Atlas skin cutaneous melanoma samples. Estimated parameters were evaluated using data-derived features and experimental knowledge, including experimental conditions and gene expressions. Simulations using optimized parameters reproduced key spatial features of the training images, such as tumor boundary complexity and tumor-tumor neighborhood structure. Together, these results demonstrate a flexible framework for ABM parameter optimization using spatial data across modalities, enabling systematic investigation of how spatial architecture influences tumor progression and immune interactions. AVAILABILITY AND IMPLEMENTATION: Source code is available at https://github.com/SysBioOncology/ AutoencoderABM under the GPL-3.0 license, with corresponding data sets at https://zenodo.org/records/19022344.

Autoencoder

Odon: an ultra-fast viewer for spatial proteomics.

MOTIVATION: Multiplexed spatial proteomics and spatial transcriptomics generate large, high-dimensional imaging datasets that are challenging to visualize efficiently, particularly at whole-slide and cohort scale. Visualization is an essential step for rapid detection of staining artefacts, such as protein aggregates or non-specific staining. RESULTS: Here, we present Odon, a native Rust desktop viewer designed for rapid, interactive exploration of multiplex imaging data on a standard laptop. Odon is primarily built around the OME-Zarr imaging format, and supports annotations via GeoJSON and GeoParquet, with secondary support for SpatialData, Xenium containers, and TIFF. Data can be stored locally or streamed directly from HTTP or S3-compatible object storage using viewport-driven tile loading. Odon incorporates a highly optimized rendering engine designed for viewport-driven tile loading and GPU-based compositing. In scripted benchmarks using synthetic multiplex OME-Zarr datasets, Odon showed lower peak memory use, lower affine-derived zoom-step error, and faster warm-start image loading than napari and QuPath under the tested conditions. Its GPU-based compositing pipeline also enables smooth rendering and interaction with >1&#x2009;000&#x2009;000 segmented cells. Odon further supports integrated visual analytics, including live thresholding and cell selection, and a mosaic mode for simultaneous viewing of hundreds of regions of interest in cohort and tissue microarray studies. Together, these features establish Odon as a high-performance platform for scalable visualization of spatial proteomics data. AVAILABILITY AND IMPLEMENTATION: Source code and compiled installers are available at https://github.com/alexcoulton/odon.

Proteomics

A consistent muscle activation strategy underlies crawling and swimming in Caenorhabditis elegans.

Although undulatory swimming is observed in many organisms, the neuromuscular basis for undulatory movement patterns is not well understood. To better understand the basis for the generation of these movement patterns, we studied muscle activity in the nematode Caenorhabditis elegans. Caenorhabditis elegans exhibits a range of locomotion patterns: in low viscosity fluids the undulation has a wavelength longer than the body and propagates rapidly, while in high viscosity fluids or on agar media the undulatory waves are shorter and slower. Theoretical treatment of observed behaviour has suggested a large change in force-posture relationships at different viscosities, but analysis of bend propagation suggests that short-range proprioceptive feedback is used to control and generate body bends. How muscles could be activated in a way consistent with both these results is unclear. We therefore combined automated worm tracking with calcium imaging to determine muscle activation strategy in a variety of external substrates. Remarkably, we observed that across locomotion patterns spanning a threefold change in wavelength, peak muscle activation occurs approximately 45&#xb0; (1/8th of a cycle) ahead of peak midline curvature. Although the location of peak force is predicted to vary widely, the activation pattern is consistent with required force in a model incorporating putative length- and velocity-dependence of muscle strength. Furthermore, a linear combination of local curvature and velocity can match the pattern of activation. This suggests that proprioception can enable the worm to swim effectively while working within the limitations of muscle biomechanics and neural control.

Alleles