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Arganda-Carreras, I.

Publications and source records attributed to Arganda-Carreras, I..

14 recordsLinked to original sources

PhenoMe: An interactive AI framework for interpretable, microscopy-driven phenotyping

Extracting meaningful biological patterns from microscopy image datasets requires tools that quantitatively connect visual similarities and experimental context. Deep learning models, and in particular novel foundation models, have the capacity to translate images into high-dimensional embeddings that can better represent complex visual patterns. Using these complex representations analytically and linking them to experimental information, it is possible to build advanced exploratory and phenotyping capabilities. Here, we present PhenoMe, an open-source, model-agnostic framework to handle pretrained foundation model-derived image representations alongside quantitative image properties and experimental metadata. PhenoMe integrates multiple scriptable and interactive workflows for embedding space visualisation, dimensionality reduction and clustering, similarity-based comparison and retrieval of representative images for each phenotype, among others. It also supports correlation analyses that link the embedding structure to interpretable image properties. We demonstrate PhenoMe's capabilities on seven public microscopy datasets, ranging from cell painting assays, nanoscale synaptic images, drug-response analyses and dynamic cell-phenotyping. These case studies show how readily available image representations can support data contextualisation, curation and analysis. Through guided notebooks, reproducible configurations, extensible model wrappers and a napari plugin, PhenoMe makes representation-based microscopy exploration accessible to researchers without dedicated technical expertise. PhenoMe lays the groundwork for applying foundation models and representation learning to microscopy data analysis.

bioinformatics↗

RnR-ExM: Robust Non-rigid Registration Challenge for Expansion Microscopy Volumes

Expansion Microscopy (ExM) enables nanoscale imaging of biological samples while preserving structural and molecular details. The Robust Non-rigid Registration Challenge for ExM (RnR-ExM) was launched to benchmark 3D registration algorithms on real-world ExM datasets. The challenge released 24 pairs of high-resolution 3D volumes from zebrafish, mouse, and C.~elegans, deliberately selected for their difficulty with standard alignment methods. To evaluate performance, we provided curated segmentation masks of nuclei and blood vessels as landmarks for half of the dataset. To encourage learning-based approaches, we released code for generating synthetic training data reflecting the deformation and appearance of the unlabeled pairs. By submission, 168 participants registered, with six teams submitting results by the deadline; the top three were invited to present at ISBI 2023. Accurate registration of ExM volumes is essential for downstream biological analyses such as multiplexed molecular mapping and cell-type-specific structural profiling. In this paper, we detail the methods and results of these top teams, highlighting current capabilities and future directions for 3D registration in ExM. All datasets and code are available at https://rnr-exm.grand-challenge.org/

neuroscience↗

Patterned membrane recycling balances apical and lateral cell surfaces to confine tissue deformation under stretch

During development, epithelia undergo large stretches, but how tissues confine the resulting deformations and stresses to specific regions is poorly understood. Here, we show that during Drosophila dorsal closure, the epidermis confines deformation through a developmentally controlled, patterned increase in apical cell surface. Dorsal cells respond to stretch by expanding their apical surface and flattening, whereas ventral cells do not expand nor flatten, even when over-stretched and despite reorganizing their actomyosin. Both shape changes require Rab11-dependent membrane recycling, showing that cell height and apical area are actively controlled rather than passively set by stretch. The Dpp/Brinker pathway restricts this remodeling to the dorsal epidermis. A vertex model shows that localized remodeling is sufficient to pattern tissue deformation and to reduce stresses, including in the ventral, non-remodeling, region. Tissue deformation is thus spatially confined by developmental patterning of the balance between apical and lateral surfaces through membrane recycling, rather than by cytoskeletal forces.

developmental biology↗

MitoEM 2.0 - A Benchmark for Challenging 3D MitochondriaInstance Segmentation from EM Images

We present MitoEM 2.0, a curated data resource for training and evaluating three-dimensional (3D) mitochondria instance segmentation in volume electron microscopy. The collection assembles multiscale vEM datasets (FIB-SEM, SBF-SEM, ssSEM) spanning diverse tissues and species, with expert-verified instance labels emphasizing biologically difficult scenarios, including dense mitochondrial packing, hyperfused networks, and thin filamentous connections with ambiguous boundaries. All releases include native-resolution volumes and standardized processed versions, per-volume metadata (voxel size, modality, tissue, splits), and official train/validation/test partitions to enable reproducible benchmarking. Annotations follow a consistent protocol with quality checks and instance reindexing. Data are provided in NIfTI with nnU-Net-compatible layout, alongside machine-readable split files and checksums. Baseline scripts support common training pipelines and size-stratified evaluation. By consolidating challenging volumes and harmonized labels, MitoEM 2.0 facilitates robust model development and fair comparison across methods while supporting reuse in bioimage analysis, algorithm benchmarking, and teaching.

neuroscience↗

3D Mapping of Intact Ovaries Reveals the Aging Dynamics of the Ovarian Reserve

Female fertility depends on a finite pool of oocytes that depletes during aging, yet the spatiotemporal dynamics of this depletion remain poorly understood. Traditional methods obscure the 3D architecture of the ovary, limiting quantitative insights. Here, we combine light-sheet microscopy, artificial intelligence (AI)-driven segmentation, and mathematical modeling to map over 85,000 oocytes in whole-ovaries across the reproductive lifespan in mouse. We find that newly activated oocytes represent a fixed fraction of the ovarian reserve, despite an age-related decline in total oocyte numbers. Spatial analysis revealed that oocytes are enriched along the lateral ovarian axis, and local oocyte density positively correlates with activation. We also uncover a bimodal distribution of oocyte sizes, suggesting a bottleneck during oogenesis. Finally, a differential equation-based model captures the kinetics of oocyte activation and loss. Our findings establish a quantitative framework for understanding ovarian aging and suggest that an organ-scale regulatory mechanism coordinates the age-related decline in oocyte numbers.

cell biology↗

Mechanosensitive and Reversible Chromatin-Lamina Dewetting Triggers Cellular Contraction During Wound Healing

Tissue wounding causes rapid mechanical changes in the epithelium, but how these changes affect intracellular organization remains unclear. Using the Drosophila embryonic epidermis, we show that wounding induces a fast, transient compaction of chromatin and its detachment ("dewetting") from the nuclear lamina in about half of the wound-edge cells. Within minutes, chromatin in these cells re-expands and re-associates with the lamina ("re-wetting"). This reversible chromatin-lamina dewetting is mechanosensitive, requiring both the LINC complex and intracellular calcium. During compaction, calcium is stored within chromatin and is later released during ATR-mediated expansion and lamina re-wetting. Chromatin re-expansion then triggers actomyosin contraction and promotes tissue repair through Jun kinase activation, straightening of the wound edge, and supracellular actin ring formation. Together, our findings reveal a multiscale mechanosensitive mechanism by which tissue-scale mechanical changes induce a reversible chromatin-lamina dewetting, leading to cellular contraction and initiation of tissue repair.

cell biology↗

DINOSim: Zero-Shot Object Detection and Semantic Segmentation on Electron Microscopy Images

We present DINOSim, a novel method for detecting and segmenting objects in microscopy images without the need for large annotated datasets or additional training. DINOSim builds on the pretrained DINOv2 image encoder, which captures semantic information from images. By comparing the encoders features of images patches to those of a user-selected reference, DINOSim generates pseudo-labels that guide object detection and segmentation. Subsequently, a k-nearest neighbors framework is then used to refine predictions across new images. Our experiments show that DINOSim can effectively identify and segment previously unseen objects in diverse microscopy datasets, offering performance comparable to supervised approaches while avoiding the need for costly manual labeling. We also investigate how different choices of user prompts selection and model size affect accuracy and generalization. To make the method widely accessible, we provide an open-source Napari plugin (github.com/AAitorG/napari-DINOSim), enabling researchers to easily apply DINOSim to their own data. Overall, DINOSim offers a fast, flexible and practical solution for bioimage analysis, particularly valuable in resource-constrained settings.

bioinformatics↗

Complexity shapes uniqueness: Neuropil volumes and synaptic clusters shape behavioural plasticity under challenging environments in the invasive Argentine ants

Adaptation to new environments is key for organisms survival, but also for their invasiveness in their introduced areas. Behaviour is considered the fastest phenotype allowing adaptation, but its plasticity can involve costs as neural development. Although individuals investment in cognition was pointed out as unnecessary for colony behaviour in eusocial insects, recent studies are highlighting the behavioural dependence on neural traits in eusocial insects. The costs of producing behavioural and neural plastic offspring could exceed the investments of eusocial insects, in which one or certain reproductives must produce multiple offspring. Thus, we wanted to analyse the link between the neuroanatomy and the behavioural variability of Linepithema humile, an invasive species organised in supercolony units containing millions of individuals, to understand its adaptive mechanisms. We repeatedly tested same aged callow workers of L. humile in behavioural tests of increasing environmental complexity and analysed the volume of their brain functional areas (neuropils) and the synaptic clusters abundance in the mushroom body calices (information processing). Given the potential large cost of plasticity, we expected to find homogeneous interindividual neuronal structures and behavioural responses. Although L. humile is considered a monomorphic species, body size conditioned behavioural and neural traits and determined individuals efficiency in exploring simple environments. Contrary to our expectations, the increase in environmental complexity revealed the behavioural plasticity of Linepithema humile workers as well as its correlation with neuropil volumes and synaptic clusters. Our results highlight the relevance of the central complex and the mushroom bodies on exploration efficiency rather than optic and olfactory lobes. Behavioural plasticity under complex environments relied on the synaptic connections of the olfactory processing area (dense lip), while individuals with higher number of synaptic connections on the visual processing area (collar) explored complex environments less efficiently. Our results suggest that behavioural differences that correlate with morphological traits might promote adaptive mechanisms in simple environments, whereas neurologically based plastic behavior may be necessary to adapt in complex environments.

animal behavior and cognition↗

Self-supervised Vision Transformers for image-to-image labeling: a BiaPy solution to the LightMyCells Challenge

Fluorescence microscopy plays a crucial role in cellular analysis but is often hindered by phototoxicity and limited spectral channels. Label-free transmitted light microscopy presents an attractive alternative, yet recovering fluorescence images from such inputs remains difficult. In this work, we address the Cell Painting problem within the LightMyCells challenge at the International Symposium on Biomedical Imaging (ISBI) 2024, aiming to predict optimally focused fluorescence images from label-free transmitted light inputs. Leveraging advancements self-supervised Vision Transformers, our method overcomes the constraints of scarce annotated biomedical data and fluorescence microscopys drawbacks. Four specialized models, each targeting a different organelle, are pretrained in a self-supervised manner to enhance model generalization. Our method, integrated within the open-source BiaPy library, contributes to the advancement of image-to-image deep-learning techniques in cellular analysis, offering a promising solution for robust and accurate fluorescence image prediction from label-free transmitted light inputs. Code and documentation can be found at https://github.com/danifranco/BiaPy and a custom tutorial to reproduce all results is available at https://biapy.readthedocs.io/en/latest/tutorials/image-to-image/lightmycells.html.

bioinformatics↗

BiaPy: A unified framework for versatile bioimage analysis with deep learning

BiaPy is an open-source library and application that streamlines the use of common deep learning approaches for bioimage analysis. Designed to simplify technical complexities, it offers an intuitive interface, zero-code notebooks, and Docker integration, catering to both users and developers. While focused on deep learning workflows for 2D and 3D image data, it enhances performance with multi-GPU capabilities, memory optimization, and scalability for large datasets. Although BiaPy does not encompass all aspects of bioimage analysis, such as visualization and manual annotation tools, it empowers researchers by providing a ready-to-use environment with customizable templates that facilitate sophisticated bioimage analysis workflows.

bioinformatics↗

DL4MicEverywhere: Deep learning for microscopy made flexible, shareable, and reproducible

Deep learning has revolutionised the analysis of extensive microscopy datasets, yet challenges persist in the widespread adoption of these techniques. Many lack access to training data, computing resources, and expertise to develop complex models. We introduce DL4MicEverywhere, advancing our previous ZeroCostDL4Mic platform, to make deep learning more accessible. DL4MicEverywhere uniquely allows flexible training and deployment across diverse computational environments by encapsulating methods in interactive Jupyter notebooks within Docker containers -a standalone virtualisation of required packages and code to reproduce a computational environment-. This enhances reproducibility and convenience. The platform includes twice as many techniques as originally provided by ZeroCostDL4Mic and enables community contributions via automated build pipelines. DL4MicEverywhere empowers participatory innovation and aims to democratise deep learning for bioimage analysis.

bioinformatics↗

CartoCell, a high-throughput pipeline for accurate 3D image analysis, unveils cell morphology patterns in epithelial cysts.

Decades of research have not yet fully explained the mechanisms of epithelial self-organization and 3D packing. Single-cell analysis of large 3D epithelial libraries is crucial for understanding the assembly and function of whole tissues. Combining 3D epithelial imaging with advanced deep learning segmentation methods is essential for enabling this high-content analysis. We introduce CartoCell, a deep learning-based pipeline that uses small datasets to generate accurate labels for hundreds of whole 3D epithelial cysts. Our method detects the realistic morphology of epithelial cells and their contacts in the 3D structure of the tissue. CartoCell enables the quantification of geometric and packing features at the cellular level. Our Single-cell Cartography approach then maps the distribution of these features on 2D plots and 3D surface maps, revealing cell morphology patterns in epithelial cysts. Additionally, we show that CartoCell can be adapted to other types of epithelial tissues. MOTIVATIONA major bottleneck in developing neural networks for cell segmentation is the need for labor-intensive manual curation in order to develop a training dataset. The present work addresses this limitation by developing an automated image analysis pipeline that utilizes small datasets to generate accurate labels of cells in complex, 3D epithelial contexts. The overall goal is to provide an automatic and feasible method to achieve high-quality epithelial reconstructions and to enable high-content analysis of morphological features, which can improve our understanding of how these tissues self-organize.

developmental biology↗

Brain virtual histology with X-ray phase-contrast tomography Part II: 3D morphologies of amyloid-β plaques in Alzheimer's disease models

While numerous transgenic mouse strains have been produced to model the formation of amyloid-{beta} (A{beta}) plaques in the brain, efficient methods for whole-brain 3D analysis of A{beta} deposits are lacking. Moreover, standard immunohistochemistry performed on brain slices precludes any shape analysis of A{beta} plaques. The present study shows how in-line (propagation-based) X-ray phase-contrast tomography (XPCT) combined with ethanol-induced brain sample dehydration enables hippocampus-wide detection and morphometric analysis of A{beta} plaques. Performed in three distinct Alzheimer mouse strains, the proposed workflow identified differences in signal intensity and 3D shape parameters: 3xTg displayed a different type of A{beta} plaques, with a larger volume and area, greater elongation, flatness and mean breadth, and more intense average signal than J20 and APP/PS1. As a label-free non-destructive technique, XPCT can be combined with standard immunohistochemistry. XPCT virtual histology could thus become instrumental in quantifying the 3D spreading and the morphological impact of seeding when studying prion-like properties of A{beta} aggregates in animal models of Alzheimers disease. This is Part II of a series of two articles reporting the value of in-line XPCT for virtual histology of the brain; Part I shows how in-line XPCT enables 3D myelin mapping in the whole rodent brain and in human autopsy brain tissue. HighlightsO_LIX-ray phase-contrast tomography (XPCT) enables whole brain detection of A{beta} plaques C_LIO_LIMorphometric parameters of A{beta} plaques may be readily retrieved from XPCT data C_LIO_LINew shape parameters were successfully extracted from three Alzheimers disease models C_LIO_LIA Fiji-based "biologist-friendly" analysis workflow is proposed and shared C_LIO_LIXPCT is a powerful virtual histology tool that requires minimal sample preparation C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=120 SRC="FIGDIR/small/436908v2_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@7c3167org.highwire.dtl.DTLVardef@18f689eorg.highwire.dtl.DTLVardef@1d9c72org.highwire.dtl.DTLVardef@a027a_HPS_FORMAT_FIGEXP M_FIG Graphical abstract C_FIG

neuroscience↗

Freeze-frame imaging of synaptic activity using SynTagMA

Information within the brain travels from neuron to neuron across synapses. At any given moment, only a few synapses within billions will be active and are thought to transmit key information about the environment, a behavior being executed or memory being recalled. Here we present SynTagMA, which marks active synapses within a ~2 s time window. Upon violet illumination, the genetically expressed tag converts from green to red fluorescence if bound to calcium. Targeted to presynaptic terminals, preSynTagMA allows discrimination between active and silent axons. Targeted to excitatory postsynapses, postSynTagMA creates a snapshot of synapses active just before photoconversion. To analyze large datasets, we developed an analysis program that automatically identifies and tracks the fluorescence of thousands of individual synapses in tissue. Together, these tools provide a high throughput method for repeatedly mapping active synapses in vitro and in vivo.

neuroscience↗