Daily Papers

In this paper, we propose a new class of metric for table structure recognition (TSR) evaluation, called grid table similarity (GriTS). Unlike prior metrics, GriTS evaluates the correctness of a predicted table directly in its natural form as a matrix. To create a similarity measure between matrices, we generalize the two-dimensional largest common substructure (2D-LCS) problem, which is NP-hard, to the 2D most similar substructures (2D-MSS) problem and propose a polynomial-time heuristic for solving it. This algorithm produces both an upper and a lower bound on the true similarity between matrices. We show using evaluation on a large real-world dataset that in practice there is almost no difference between these bounds. We compare GriTS to other metrics and empirically validate that matrix similarity exhibits more desirable behavior than alternatives for TSR performance evaluation. Finally, GriTS unifies all three subtasks of cell topology recognition, cell location recognition, and cell content recognition within the same framework, which simplifies the evaluation and enables more meaningful comparisons across different types of TSR approaches. Code will be released at https://github.com/microsoft/table-transformer.

3D cellular image segmentation methods are commonly divided into non-2D-based and 2D-based approaches, the latter reconstructing 3D shapes from the segmentation results of 2D layers. However, errors in 2D results often propagate, leading to oversegmentations in the final 3D results. To tackle this issue, we introduce an interpretable geometric framework that addresses the oversegmentations by correcting the 2D segmentation results based on geometric information from adjacent layers. Leveraging both geometric (layer-to-layer, 2D) and topological (3D shape) features, we use binary classification to determine whether neighboring cells should be stitched. We develop a pre-trained classifier on public plant cell datasets and validate its performance on animal cell datasets, confirming its effectiveness in correcting oversegmentations under the transfer learning setting. Furthermore, we demonstrate that our framework can be extended to correcting oversegmentation on non-2D-based methods. A clear pipeline is provided for end-users to build the pre-trained model to any labeled dataset.

Leaf-lesion segmentation is topology-sensitive: small merges, splits, or false holes can be biologically meaningful descriptors of biochemical pathways, yet they are weakly penalized by standard pixel-wise losses in Euclidean latents. I explore HyperTopo-Adapters, a lightweight, parameter-efficient head trained on top of a frozen vision encoder, which embeds features on a product manifold -- hyperbolic + Euclidean + spherical (H + E + S) -- to encourage hierarchical separation (H), local linear detail (E), and global closure (S). A topology prior complements Dice/BCE in two forms: (i) persistent-homology (PH) distance for evaluation and selection, and (ii) a differentiable surrogate that combines a soft Euler-characteristic match with total variation regularization for stable training. I introduce warm-ups for both the hyperbolic contrastive term and the topology prior, per-sample evaluation of structure-aware metrics (Boundary-F1, Betti errors, PD distance), and a min-PD within top-K Dice rule for checkpoint selection. On a Kaggle leaf-lesion dataset (N=2,940), early results show consistent gains in boundary and topology metrics (reducing Delta beta_1 hole error by 9%) while Dice/IoU remain competitive. The study is diagnostic by design: I report controlled ablations (curvature learning, latent dimensions, contrastive temperature, surrogate settings), and ongoing tests varying encoder strength (ResNet-50, DeepLabV3, DINOv2/v3), input resolution, PH weight, and partial unfreezing of late blocks. The contribution is an open, reproducible train/eval suite (available at https://github.com/ChimdiWalter/HyperTopo-Adapters) that isolates geometric/topological priors and surfaces failure modes to guide stronger, topology-preserving architectures.

Geometric alignment appears in a variety of applications, ranging from domain adaptation, optimal transport, and normalizing flows in machine learning; optical flow and learned augmentation in computer vision and deformable registration within biomedical imaging. A recurring challenge is the alignment of domains whose topology is not the same; a problem that is routinely ignored, potentially introducing bias in downstream analysis. As a first step towards solving such alignment problems, we propose an unsupervised algorithm for the detection of changes in image topology. The model is based on a conditional variational auto-encoder and detects topological changes between two images during the registration step. We account for both topological changes in the image under spatial variation and unexpected transformations. Our approach is validated on two tasks and datasets: detection of topological changes in microscopy images of cells, and unsupervised anomaly detection brain imaging.

During developmental processes such as embryogenesis, how a group of cells fold into specific structures, is a central question in biology that defines how living organisms form. Establishing tissue-level morphology critically relies on how every single cell decides to position itself relative to its neighboring cells. Despite its importance, it remains a major challenge to understand and predict the behavior of every cell within the living tissue over time during such intricate processes. To tackle this question, we propose a geometric deep learning model that can predict multicellular folding and embryogenesis, accurately capturing the highly convoluted spatial interactions among cells. We demonstrate that multicellular data can be represented with both granular and foam-like physical pictures through a unified graph data structure, considering both cellular interactions and cell junction networks. We successfully use our model to achieve two important tasks, interpretable 4-D morphological sequence alignment, and predicting local cell rearrangements before they occur at single-cell resolution. Furthermore, using an activation map and ablation studies, we demonstrate that cell geometries and cell junction networks together regulate local cell rearrangement which is critical for embryo morphogenesis. This approach provides a novel paradigm to study morphogenesis, highlighting a unified data structure and harnessing the power of geometric deep learning to accurately model the mechanisms and behaviors of cells during development. It offers a pathway toward creating a unified dynamic morphological atlas for a variety of developmental processes such as embryogenesis.

Cell identity encompasses various semantic aspects of a cell, including cell type, pathway information, disease information, and more, which are essential for biologists to gain insights into its biological characteristics. Understanding cell identity from the transcriptomic data, such as annotating cell types, has become an important task in bioinformatics. As these semantic aspects are determined by human experts, it is impossible for AI models to effectively carry out cell identity understanding tasks without the supervision signals provided by single-cell and label pairs. The single-cell pre-trained language models (PLMs) currently used for this task are trained only on a single modality, transcriptomics data, lack an understanding of cell identity knowledge. As a result, they have to be fine-tuned for downstream tasks and struggle when lacking labeled data with the desired semantic labels. To address this issue, we propose an innovative solution by constructing a unified representation of single-cell data and natural language during the pre-training phase, allowing the model to directly incorporate insights related to cell identity. More specifically, we introduce LangCell, the first Language-Cell pre-training framework. LangCell utilizes texts enriched with cell identity information to gain a profound comprehension of cross-modal knowledge. Results from experiments conducted on different benchmarks show that LangCell is the only single-cell PLM that can work effectively in zero-shot cell identity understanding scenarios, and also significantly outperforms existing models in few-shot and fine-tuning cell identity understanding scenarios.

Accurate detection and segmentation of cell nuclei in volumetric (3D) fluorescence microscopy datasets is an important step in many biomedical research projects. Although many automated methods for these tasks exist, they often struggle for images with low signal-to-noise ratios and/or dense packing of nuclei. It was recently shown for 2D microscopy images that these issues can be alleviated by training a neural network to directly predict a suitable shape representation (star-convex polygon) for cell nuclei. In this paper, we adopt and extend this approach to 3D volumes by using star-convex polyhedra to represent cell nuclei and similar shapes. To that end, we overcome the challenges of 1) finding parameter-efficient star-convex polyhedra representations that can faithfully describe cell nuclei shapes, 2) adapting to anisotropic voxel sizes often found in fluorescence microscopy datasets, and 3) efficiently computing intersections between pairs of star-convex polyhedra (required for non-maximum suppression). Although our approach is quite general, since star-convex polyhedra include common shapes like bounding boxes and spheres as special cases, our focus is on accurate detection and segmentation of cell nuclei. Finally, we demonstrate on two challenging datasets that our approach (StarDist-3D) leads to superior results when compared to classical and deep learning based methods.

In this paper, we propose HiPoNet, an end-to-end differentiable neural network for regression, classification, and representation learning on high-dimensional point clouds. Our work is motivated by single-cell data which can have very high-dimensionality --exceeding the capabilities of existing methods for point clouds which are mostly tailored for 3D data. Moreover, modern single-cell and spatial experiments now yield entire cohorts of datasets (i.e., one data set for every patient), necessitating models that can process large, high-dimensional point-clouds at scale. Most current approaches build a single nearest-neighbor graph, discarding important geometric and topological information. In contrast, HiPoNet models the point-cloud as a set of higher-order simplicial complexes, with each particular complex being created using a reweighting of features. This method thus generates multiple constructs corresponding to different views of high-dimensional data, which in biology offers the possibility of disentangling distinct cellular processes. It then employs simplicial wavelet transforms to extract multiscale features, capturing both local and global topology from each view. We show that geometric and topological information is preserved in this framework both theoretically and empirically. We showcase the utility of HiPoNet on point-cloud level tasks, involving classification and regression of entire point-clouds in data cohorts. Experimentally, we find that HiPoNet outperforms other point-cloud and graph-based models on single-cell data. We also apply HiPoNet to spatial transcriptomics datasets using spatial coordinates as one of the views. Overall, HiPoNet offers a robust and scalable solution for high-dimensional data analysis.

Latent Graph Inference (LGI) relaxed the reliance of Graph Neural Networks (GNNs) on a given graph topology by dynamically learning it. However, most of LGI methods assume to have a (noisy, incomplete, improvable, ...) input graph to rewire and can solely learn regular graph topologies. In the wake of the success of Topological Deep Learning (TDL), we study Latent Topology Inference (LTI) for learning higher-order cell complexes (with sparse and not regular topology) describing multi-way interactions between data points. To this aim, we introduce the Differentiable Cell Complex Module (DCM), a novel learnable function that computes cell probabilities in the complex to improve the downstream task. We show how to integrate DCM with cell complex message passing networks layers and train it in a end-to-end fashion, thanks to a two-step inference procedure that avoids an exhaustive search across all possible cells in the input, thus maintaining scalability. Our model is tested on several homophilic and heterophilic graph datasets and it is shown to outperform other state-of-the-art techniques, offering significant improvements especially in cases where an input graph is not provided.

Traditional fluorescence staining is phototoxic to live cells, slow, and expensive; thus, the subcellular structure prediction (SSP) from transmitted light (TL) images is emerging as a label-free, faster, low-cost alternative. However, existing approaches utilize 3D networks for one-to-one voxel level dense prediction, which necessitates a frequent and time-consuming Z-axis imaging process. Moreover, 3D convolutions inevitably lead to significant computation and GPU memory overhead. Therefore, we propose an efficient framework, SparseSSP, predicting fluorescent intensities within the target voxel grid in an efficient paradigm instead of relying entirely on 3D topologies. In particular, SparseSSP makes two pivotal improvements to prior works. First, SparseSSP introduces a one-to-many voxel mapping paradigm, which permits the sparse TL slices to reconstruct the subcellular structure. Secondly, we propose a hybrid dimensions topology, which folds the Z-axis information into channel features, enabling the 2D network layers to tackle SSP under low computational cost. We conduct extensive experiments to validate the effectiveness and advantages of SparseSSP on diverse sparse imaging ratios, and our approach achieves a leading performance compared to pure 3D topologies. SparseSSP reduces imaging frequencies compared to previous dense-view SSP (i.e., the number of imaging is reduced up to 87.5% at most), which is significant in visualizing rapid biological dynamics on low-cost devices and samples.

Blood vessel networks in the brain play a crucial role in stroke research, where understanding their topology is essential for analyzing blood flow dynamics. However, extracting detailed topological vessel network information from microscopy data remains a significant challenge, mainly due to the scarcity of labeled training data and the need for high topological accuracy. This work combines synthetic data generation with deep learning to automatically extract vessel networks as graphs from volumetric microscopy data. To combat data scarcity, we introduce a comprehensive pipeline for generating large-scale synthetic datasets that mirror the characteristics of real vessel networks. Our three-stage approach progresses from abstract graph generation through vessel mask creation to realistic medical image synthesis, incorporating biological constraints and imaging artifacts at each stage. Using this synthetic data, we develop a two-stage deep learning pipeline of 3D U-Net-based models for node detection and edge prediction. Fine-tuning on real microscopy data shows promising adaptation, improving edge prediction F1 scores from 0.496 to 0.626 by training on merely 5 manually labeled samples. These results suggest that automated vessel network extraction is becoming practically feasible, opening new possibilities for large-scale vascular analysis in stroke research.

Precise cell classification is essential in biomedical diagnostics and therapeutic monitoring, particularly for identifying diverse cell types involved in various diseases. Traditional cell classification methods such as flow cytometry depend on molecular labeling which is often costly, time-intensive, and can alter cell integrity. To overcome these limitations, we present a label-free machine learning framework for cell classification, designed for real-time sorting applications using bright-field microscopy images. This approach leverages a teacher-student model architecture enhanced by knowledge distillation, achieving high efficiency and scalability across different cell types. Demonstrated through a use case of classifying lymphocyte subsets, our framework accurately classifies T4, T8, and B cell types with a dataset of 80,000 preprocessed images, accessible via an open-source Python package for easy adaptation. Our teacher model attained 98\% accuracy in differentiating T4 cells from B cells and 93\% accuracy in zero-shot classification between T8 and B cells. Remarkably, our student model operates with only 0.02\% of the teacher model's parameters, enabling field-programmable gate array (FPGA) deployment. Our FPGA-accelerated student model achieves an ultra-low inference latency of just 14.5~μs and a complete cell detection-to-sorting trigger time of 24.7~μs, delivering 12x and 40x improvements over the previous state-of-the-art real-time cell analysis algorithm in inference and total latency, respectively, while preserving accuracy comparable to the teacher model. This framework provides a scalable, cost-effective solution for lymphocyte classification, as well as a new SOTA real-time cell sorting implementation for rapid identification of subsets using in situ deep learning on off-the-shelf computing hardware.

A central question for neuroscience is how to characterize brain representations of perceptual and cognitive content. An ideal characterization should distinguish different functional regions with robustness to noise and idiosyncrasies of individual brains that do not correspond to computational differences. Previous studies have characterized brain representations by their representational geometry, which is defined by the representational dissimilarity matrix (RDM), a summary statistic that abstracts from the roles of individual neurons (or responses channels) and characterizes the discriminability of stimuli. Here we explore a further step of abstraction: from the geometry to the topology of brain representations. We propose topological representational similarity analysis (tRSA), an extension of representational similarity analysis (RSA) that uses a family of geo-topological summary statistics that generalizes the RDM to characterize the topology while de-emphasizing the geometry. We evaluate this new family of statistics in terms of the sensitivity and specificity for model selection using both simulations and functional MRI (fMRI) data. In the simulations, the ground truth is a data-generating layer representation in a neural network model and the models are the same and other layers in different model instances (trained from different random seeds). In fMRI, the ground truth is a visual area and the models are the same and other areas measured in different subjects. Results show that topology-sensitive characterizations of population codes are robust to noise and interindividual variability and maintain excellent sensitivity to the unique representational signatures of different neural network layers and brain regions.

The caliber and configuration of retinal blood vessels serve as important biomarkers for various diseases and medical conditions. A thorough analysis of the retinal vasculature requires the segmentation of the blood vessels and their classification into arteries and veins, typically performed on color fundus images obtained by retinography. However, manually performing these tasks is labor-intensive and prone to human error. While several automated methods have been proposed to address this task, the current state of art faces challenges due to manifest classification errors affecting the topological consistency of segmentation maps. In this work, we introduce RRWNet, a novel end-to-end deep learning framework that addresses this limitation. The framework consists of a fully convolutional neural network that recursively refines semantic segmentation maps, correcting manifest classification errors and thus improving topological consistency. In particular, RRWNet is composed of two specialized subnetworks: a Base subnetwork that generates base segmentation maps from the input images, and a Recursive Refinement subnetwork that iteratively and recursively improves these maps. Evaluation on three different public datasets demonstrates the state-of-the-art performance of the proposed method, yielding more topologically consistent segmentation maps with fewer manifest classification errors than existing approaches. In addition, the Recursive Refinement module within RRWNet proves effective in post-processing segmentation maps from other methods, further demonstrating its potential. The model code, weights, and predictions will be publicly available at https://github.com/j-morano/rrwnet.

Topological data analysis (TDA) is an area of data science that focuses on using invariants from algebraic topology to provide multiscale shape descriptors for geometric data sets such as point clouds. One of the most important such descriptors is {\em persistent homology}, which encodes the change in shape as a filtration parameter changes; a typical parameter is the feature scale. For many data sets, it is useful to simultaneously vary multiple filtration parameters, for example feature scale and density. While the theoretical properties of single parameter persistent homology are well understood, less is known about the multiparameter case. In particular, a central question is the problem of representing multiparameter persistent homology by elements of a vector space for integration with standard machine learning algorithms. Existing approaches to this problem either ignore most of the multiparameter information to reduce to the one-parameter case or are heuristic and potentially unstable in the face of noise. In this article, we introduce a new general representation framework that leverages recent results on {\em decompositions} of multiparameter persistent homology. This framework is rich in information, fast to compute, and encompasses previous approaches. Moreover, we establish theoretical stability guarantees under this framework as well as efficient algorithms for practical computation, making this framework an applicable and versatile tool for analyzing geometric and point cloud data. We validate our stability results and algorithms with numerical experiments that demonstrate statistical convergence, prediction accuracy, and fast running times on several real data sets.

Adversarially perturbed images of text can cause sophisticated OCR systems to produce misleading or incorrect transcriptions from seemingly invisible changes to humans. Some of these perturbations even survive physical capture, posing security risks to high-stakes applications such as document processing, license plate recognition, and automated compliance systems. Existing defenses, such as adversarial training, input preprocessing, or post-recognition correction, are often model-specific, computationally expensive, and affect performance on unperturbed inputs while remaining vulnerable to unseen or adaptive attacks. To address these challenges, TopoReformer is introduced, a model-agnostic reformation pipeline that mitigates adversarial perturbations while preserving the structural integrity of text images. Topology studies properties of shapes and spaces that remain unchanged under continuous deformations, focusing on global structures such as connectivity, holes, and loops rather than exact distance. Leveraging these topological features, TopoReformer employs a topological autoencoder to enforce manifold-level consistency in latent space and improve robustness without explicit gradient regularization. The proposed method is benchmarked on EMNIST, MNIST, against standard adversarial attacks (FGSM, PGD, Carlini-Wagner), adaptive attacks (EOT, BDPA), and an OCR-specific watermark attack (FAWA).

Cell instance segmentation (CIS) is crucial for identifying individual cell morphologies in histopathological images, providing valuable insights for biological and medical research. While unsupervised CIS (UCIS) models aim to reduce the heavy reliance on labor-intensive image annotations, they fail to accurately capture cell boundaries, causing missed detections and poor performance. Recognizing the absence of error-free instances as a key limitation, we present COIN (COnfidence score-guided INstance distillation), a novel annotation-free framework with three key steps: (1) Increasing the sensitivity for the presence of error-free instances via unsupervised semantic segmentation with optimal transport, leveraging its ability to discriminate spatially minor instances, (2) Instance-level confidence scoring to measure the consistency between model prediction and refined mask and identify highly confident instances, offering an alternative to ground truth annotations, and (3) Progressive expansion of confidence with recursive self-distillation. Extensive experiments across six datasets show COIN outperforming existing UCIS methods, even surpassing semi- and weakly-supervised approaches across all metrics on the MoNuSeg and TNBC datasets. The code is available at https://github.com/shjo-april/COIN.

Object segmentation is an important step in the workflow of computational pathology. Deep learning based models generally require large amount of labeled data for precise and reliable prediction. However, collecting labeled data is expensive because it often requires expert knowledge, particularly in medical imaging domain where labels are the result of a time-consuming analysis made by one or more human experts. As nuclei, cells and glands are fundamental objects for downstream analysis in computational pathology/cytology, in this paper we propose a simple CNN-based approach to speed up collecting annotations for these objects which requires minimum interaction from the annotator. We show that for nuclei and cells in histology and cytology images, one click inside each object is enough for NuClick to yield a precise annotation. For multicellular structures such as glands, we propose a novel approach to provide the NuClick with a squiggle as a guiding signal, enabling it to segment the glandular boundaries. These supervisory signals are fed to the network as auxiliary inputs along with RGB channels. With detailed experiments, we show that NuClick is adaptable to the object scale, robust against variations in the user input, adaptable to new domains, and delivers reliable annotations. An instance segmentation model trained on masks generated by NuClick achieved the first rank in LYON19 challenge. As exemplar outputs of our framework, we are releasing two datasets: 1) a dataset of lymphocyte annotations within IHC images, and 2) a dataset of segmented WBCs in blood smear images.

Cell instance segmentation in fluorescence microscopy images is becoming essential for cancer dynamics and prognosis. Data extracted from cancer dynamics allows to understand and accurately model different metabolic processes such as proliferation. This enables customized and more precise cancer treatments. However, accurate cell instance segmentation, necessary for further cell tracking and behavior analysis, is still challenging in scenarios with high cell concentration and overlapping edges. Within this framework, we propose a novel cell instance segmentation approach based on the well-known U-Net architecture. To enforce the learning of morphological information per pixel, a deep distance transformer (DDT) acts as a back-bone model. The DDT output is subsequently used to train a top-model. The following top-models are considered: a three-class (e.g., foreground, background and cell border) U-net, and a watershed transform. The obtained results suggest a performance boost over traditional U-Net architectures. This opens an interesting research line around the idea of injecting morphological information into a fully convolutional model.

Efficient Human Epithelial-2 (HEp-2) cell image classification can facilitate the diagnosis of many autoimmune diseases. This paper presents an automatic framework for this classification task, by utilizing the deep convolutional neural networks (CNNs) which have recently attracted intensive attention in visual recognition. This paper elaborates the important components of this framework, discusses multiple key factors that impact the efficiency of training a deep CNN, and systematically compares this framework with the well-established image classification models in the literature. Experiments on benchmark datasets show that i) the proposed framework can effectively outperform existing models by properly applying data augmentation; ii) our CNN-based framework demonstrates excellent adaptability across different datasets, which is highly desirable for classification under varying laboratory settings. Our system is ranked high in the cell image classification competition hosted by ICPR 2014.

Persistent homology, a technique from computational topology, has recently shown strong empirical performance in the context of graph classification. Being able to capture long range graph properties via higher-order topological features, such as cycles of arbitrary length, in combination with multi-scale topological descriptors, has improved predictive performance for data sets with prominent topological structures, such as molecules. At the same time, the theoretical properties of persistent homology have not been formally assessed in this context. This paper intends to bridge the gap between computational topology and graph machine learning by providing a brief introduction to persistent homology in the context of graphs, as well as a theoretical discussion and empirical analysis of its expressivity for graph learning tasks.

We present EuLearn, the first surface datasets equitably representing a diversity of topological types. We designed our embedded surfaces of uniformly varying genera relying on random knots, thus allowing our surfaces to knot with themselves. EuLearn contributes new topological datasets of meshes, point clouds, and scalar fields in 3D. We aim to facilitate the training of machine learning systems that can discern topological features. We experimented with specific emblematic 3D neural network architectures, finding that their vanilla implementations perform poorly on genus classification. To enhance performance, we developed a novel, non-Euclidean, statistical sampling method adapted to graph and manifold data. We also introduce adjacency-informed adaptations of PointNet and Transformer architectures that rely on our non-Euclidean sampling strategy. Our results demonstrate that incorporating topological information into deep learning workflows significantly improves performance on these otherwise challenging EuLearn datasets.

Machine learning for point clouds has been attracting much attention, with many applications in various fields, such as shape recognition and material science. For enhancing the accuracy of such machine learning methods, it is often effective to incorporate global topological features, which are typically extracted by persistent homology. In the calculation of persistent homology for a point cloud, we choose a filtration for the point cloud, an increasing sequence of spaces. Since the performance of machine learning methods combined with persistent homology is highly affected by the choice of a filtration, we need to tune it depending on data and tasks. In this paper, we propose a framework that learns a filtration adaptively with the use of neural networks. In order to make the resulting persistent homology isometry-invariant, we develop a neural network architecture with such invariance. Additionally, we show a theoretical result on a finite-dimensional approximation of filtration functions, which justifies the proposed network architecture. Experimental results demonstrated the efficacy of our framework in several classification tasks.

Recent advances have discussed cell complexes as ideal learning representations. However, there is a lack of available machine learning methods suitable for learning on CW complexes. In this paper, we derive an explicit expression for the Wasserstein distance between cell complex signal distributions in terms of a Hodge-Laplacian matrix. This leads to a structurally meaningful measure to compare CW complexes and define the optimal transportation map. In order to simultaneously include both feature and structure information, we extend the Fused Gromov-Wasserstein distance to CW complexes. Finally, we introduce novel kernels over the space of probability measures on CW complexes based on the dual formulation of optimal transport.

In this paper, we propose a hybrid approach for multi-object microbial cell segmentation. The approach combines an ML-based detection with a geometry-aware variational-based segmentation using B-splines that are parametrized based on a geometric model of the cell shape. The detection is done first using YOLOv5. In a second step, each detected cell is segmented individually. Thus, the segmentation only needs to be done on a per-cell basis, which makes it amenable to a variational approach that incorporates prior knowledge on the geometry. Here, the contour of the segmentation is modelled as closed uniform cubic B-spline, whose control points are parametrized using the known cell geometry. Compared to purely ML-based segmentation approaches, which need accurate segmentation maps as training data that are very laborious to produce, our method just needs bounding boxes as training data. Still, the proposed method performs on par with ML-based segmentation approaches usually used in this context. We study the performance of the proposed method on time-lapse microscopy data of Corynebacterium glutamicum.

A suitable feature representation that can both preserve the data intrinsic information and reduce data complexity and dimensionality is key to the performance of machine learning models. Deeply rooted in algebraic topology, persistent homology (PH) provides a delicate balance between data simplification and intrinsic structure characterization, and has been applied to various areas successfully. However, the combination of PH and machine learning has been hindered greatly by three challenges, namely topological representation of data, PH-based distance measurements or metrics, and PH-based feature representation. With the development of topological data analysis, progresses have been made on all these three problems, but widely scattered in different literatures. In this paper, we provide a systematical review of PH and PH-based supervised and unsupervised models from a computational perspective. Our emphasizes are the recent development of mathematical models and tools, including PH softwares and PH-based functions, feature representations, kernels, and similarity models. Essentially, this paper can work as a roadmap for the practical application of PH-based machine learning tools. Further, we consider different topological feature representations in different machine learning models, and investigate their impacts on the protein secondary structure classification.

In biological research, fluorescence staining is a key technique to reveal the locations and morphology of subcellular structures. However, it is slow, expensive, and harmful to cells. In this paper, we model it as a deep learning task termed subcellular structure prediction (SSP), aiming to predict the 3D fluorescent images of multiple subcellular structures from a 3D transmitted-light image. Unfortunately, due to the limitations of current biotechnology, each image is partially labeled in SSP. Besides, naturally, subcellular structures vary considerably in size, which causes the multi-scale issue of SSP. To overcome these challenges, we propose Re-parameterizing Mixture-of-Diverse-Experts (RepMode), a network that dynamically organizes its parameters with task-aware priors to handle specified single-label prediction tasks. In RepMode, the Mixture-of-Diverse-Experts (MoDE) block is designed to learn the generalized parameters for all tasks, and gating re-parameterization (GatRep) is performed to generate the specialized parameters for each task, by which RepMode can maintain a compact practical topology exactly like a plain network, and meanwhile achieves a powerful theoretical topology. Comprehensive experiments show that RepMode can achieve state-of-the-art overall performance in SSP.

Extracting single-cell information from microscopy data requires accurate instance-wise segmentations. Obtaining pixel-wise segmentations from microscopy imagery remains a challenging task, especially with the added complexity of microstructured environments. This paper presents a novel dataset for segmenting yeast cells in microstructures. We offer pixel-wise instance segmentation labels for both cells and trap microstructures. In total, we release 493 densely annotated microscopy images. To facilitate a unified comparison between novel segmentation algorithms, we propose a standardized evaluation strategy for our dataset. The aim of the dataset and evaluation strategy is to facilitate the development of new cell segmentation approaches. The dataset is publicly available at https://christophreich1996.github.io/yeast_in_microstructures_dataset/ .

Subcellular localization is a crucial biological task for drug target identification and function annotation. Although it has been biologically realized that subcellular localization is closely associated with protein structure, no existing dataset offers comprehensive 3D structural information with detailed subcellular localization annotations, thus severely hindering the application of promising structure-based models on this task. To address this gap, we introduce a new benchmark called CAPSUL, a Comprehensive humAn Protein benchmark for SUbcellular Localization. It features a dataset that integrates diverse 3D structural representations with fine-grained subcellular localization annotations carefully curated by domain experts. We evaluate this benchmark using a variety of state-of-the-art sequence-based and structure-based models, showcasing the importance of involving structural features in this task. Furthermore, we explore reweighting and single-label classification strategies to facilitate future investigation on structure-based methods for this task. Lastly, we showcase the powerful interpretability of structure-based methods through a case study on the Golgi apparatus, where we discover a decisive localization pattern α-helix from attention mechanisms, demonstrating the potential for bridging the gap with intuitive biological interpretability and paving the way for data-driven discoveries in cell biology.

Cell instance segmentation in cytology images has significant importance for biology analysis and cancer screening, while remains challenging due to 1) the extensive overlapping translucent cell clusters that cause the ambiguous boundaries, and 2) the confusion of mimics and debris as nuclei. In this work, we proposed a De-overlapping Network (DoNet) in a decompose-and-recombined strategy. A Dual-path Region Segmentation Module (DRM) explicitly decomposes the cell clusters into intersection and complement regions, followed by a Semantic Consistency-guided Recombination Module (CRM) for integration. To further introduce the containment relationship of the nucleus in the cytoplasm, we design a Mask-guided Region Proposal Strategy (MRP) that integrates the cell attention maps for inner-cell instance prediction. We validate the proposed approach on ISBI2014 and CPS datasets. Experiments show that our proposed DoNet significantly outperforms other state-of-the-art (SOTA) cell instance segmentation methods. The code is available at https://github.com/DeepDoNet/DoNet.

Detecting and classifying cells in histopathology H\&E stained whole-slide images is a core task in computational pathology, as it provides valuable insight into the tumor microenvironment. In this work we investigate the impact of ground truth formats on the models performance. Additionally, cell-tissue interactions are considered by providing tissue segmentation predictions as input to the cell detection model. We find that a "soft", probability-map instance segmentation ground truth leads to best model performance. Combined with cell-tissue interaction and test-time augmentation our Soft Cell-Tissue-Model (SoftCTM) achieves 0.7172 mean F1-Score on the Overlapped Cell On Tissue (OCELOT) test set, achieving the third best overall score in the OCELOT 2023 Challenge. The source code for our approach is made publicly available at https://github.com/lely475/ocelot23algo.

Nucleus segmentation is a challenging task due to the crowded distribution and blurry boundaries of nuclei. Recent approaches represent nuclei by means of polygons to differentiate between touching and overlapping nuclei and have accordingly achieved promising performance. Each polygon is represented by a set of centroid-to-boundary distances, which are in turn predicted by features of the centroid pixel for a single nucleus. However, using the centroid pixel alone does not provide sufficient contextual information for robust prediction and thus degrades the segmentation accuracy. To handle this problem, we propose a Context-aware Polygon Proposal Network (CPP-Net) for nucleus segmentation. First, we sample a point set rather than one single pixel within each cell for distance prediction. This strategy substantially enhances contextual information and thereby improves the robustness of the prediction. Second, we propose a Confidence-based Weighting Module, which adaptively fuses the predictions from the sampled point set. Third, we introduce a novel Shape-Aware Perceptual (SAP) loss that constrains the shape of the predicted polygons. Here, the SAP loss is based on an additional network that is pre-trained by means of mapping the centroid probability map and the pixel-to-boundary distance maps to a different nucleus representation. Extensive experiments justify the effectiveness of each component in the proposed CPP-Net. Finally, CPP-Net is found to achieve state-of-the-art performance on three publicly available databases, namely DSB2018, BBBC06, and PanNuke. Code of this paper is available at \url{https://github.com/csccsccsccsc/cpp-net

Segmenting cells and tracking their motion over time is a common task in biomedical applications. However, predicting accurate instance-wise segmentation and cell motions from microscopy imagery remains a challenging task. Using microstructured environments for analyzing single cells in a constant flow of media adds additional complexity. While large-scale labeled microscopy datasets are available, we are not aware of any large-scale dataset, including both cells and microstructures. In this paper, we introduce the trapped yeast cell (TYC) dataset, a novel dataset for understanding instance-level semantics and motions of cells in microstructures. We release 105 dense annotated high-resolution brightfield microscopy images, including about 19k instance masks. We also release 261 curated video clips composed of 1293 high-resolution microscopy images to facilitate unsupervised understanding of cell motions and morphology. TYC offers ten times more instance annotations than the previously largest dataset, including cells and microstructures. Our effort also exceeds previous attempts in terms of microstructure variability, resolution, complexity, and capturing device (microscopy) variability. We facilitate a unified comparison on our novel dataset by introducing a standardized evaluation strategy. TYC and evaluation code are publicly available under CC BY 4.0 license.

The digitization of histology slides has revolutionized pathology, providing massive datasets for cancer diagnosis and research. Contrastive self-supervised and vision-language models have been shown to effectively mine large pathology datasets to learn discriminative representations. On the other hand, generative models, capable of synthesizing realistic and diverse images, present a compelling solution to address unique problems in pathology that involve synthesizing images; overcoming annotated data scarcity, enabling privacy-preserving data sharing, and performing inherently generative tasks, such as virtual staining. We introduce PixCell, the first diffusion-based generative foundation model for histopathology. We train PixCell on PanCan-30M, a vast, diverse dataset derived from 69,184 H\&E-stained whole slide images covering various cancer types. We employ a progressive training strategy and a self-supervision-based conditioning that allows us to scale up training without any annotated data. PixCell generates diverse and high-quality images across multiple cancer types, which we find can be used in place of real data to train a self-supervised discriminative model. Synthetic images shared between institutions are subject to fewer regulatory barriers than would be the case with real clinical images. Furthermore, we showcase the ability to precisely control image generation using a small set of annotated images, which can be used for both data augmentation and educational purposes. Testing on a cell segmentation task, a mask-guided PixCell enables targeted data augmentation, improving downstream performance. Finally, we demonstrate PixCell's ability to use H\&E structural staining to infer results from molecular marker studies; we use this capability to infer IHC staining from H\&E images. Our trained models are publicly released to accelerate research in computational pathology.

Feature vectors provided by pre-trained deep artificial neural networks have become a dominant source for image representation in recent literature. Their contribution to the performance of image analysis can be improved through finetuning. As an ultimate solution, one might even train a deep network from scratch with the domain-relevant images, a highly desirable option which is generally impeded in pathology by lack of labeled images and the computational expense. In this study, we propose a new network, namely KimiaNet, that employs the topology of the DenseNet with four dense blocks, fine-tuned and trained with histopathology images in different configurations. We used more than 240,000 image patches with 1000x1000 pixels acquired at 20x magnification through our proposed "highcellularity mosaic" approach to enable the usage of weak labels of 7,126 whole slide images of formalin-fixed paraffin-embedded human pathology samples publicly available through the The Cancer Genome Atlas (TCGA) repository. We tested KimiaNet using three public datasets, namely TCGA, endometrial cancer images, and colorectal cancer images by evaluating the performance of search and classification when corresponding features of different networks are used for image representation. As well, we designed and trained multiple convolutional batch-normalized ReLU (CBR) networks. The results show that KimiaNet provides superior results compared to the original DenseNet and smaller CBR networks when used as feature extractor to represent histopathology images.

Automated and semi-automated techniques in biomedical electron microscopy (EM) enable the acquisition of large datasets at a high rate. Segmentation methods are therefore essential to analyze and interpret these large volumes of data, which can no longer completely be labeled manually. In recent years, deep learning algorithms achieved impressive results in both pixel-level labeling (semantic segmentation) and the labeling of separate instances of the same class (instance segmentation). In this review, we examine how these algorithms were adapted to the task of segmenting cellular and sub-cellular structures in EM images. The special challenges posed by such images and the network architectures that overcame some of them are described. Moreover, a thorough overview is also provided on the notable datasets that contributed to the proliferation of deep learning in EM. Finally, an outlook of current trends and future prospects of EM segmentation is given, especially in the area of label-free learning.

With the rapid development of computational pathology, many AI-assisted diagnostic tasks have emerged. Cellular nuclei segmentation can segment various types of cells for downstream analysis, but it relies on predefined categories and lacks flexibility. Moreover, pathology visual question answering can perform image-level understanding but lacks region-level detection capability. To address this, we propose a new benchmark called Pathology Visual Grounding (PathVG), which aims to detect regions based on expressions with different attributes. To evaluate PathVG, we create a new dataset named RefPath which contains 27,610 images with 33,500 language-grounded boxes. Compared to visual grounding in other domains, PathVG presents pathological images at multi-scale and contains expressions with pathological knowledge. In the experimental study, we found that the biggest challenge was the implicit information underlying the pathological expressions. Based on this, we proposed Pathology Knowledge-enhanced Network (PKNet) as the baseline model for PathVG. PKNet leverages the knowledge-enhancement capabilities of Large Language Models (LLMs) to convert pathological terms with implicit information into explicit visual features, and fuses knowledge features with expression features through the designed Knowledge Fusion Module (KFM). The proposed method achieves state-of-the-art performance on the PathVG benchmark.

This paper presents advancements in automated early-stage prediction of the success of reprogramming human induced pluripotent stem cells (iPSCs) as a potential source for regenerative cell therapies.The minuscule success rate of iPSC-reprogramming of around 0.01% to 0.1% makes it labor-intensive, time-consuming, and exorbitantly expensive to generate a stable iPSC line. Since that requires culturing of millions of cells and intense biological scrutiny of multiple clones to identify a single optimal clone. The ability to reliably predict which cells are likely to establish as an optimal iPSC line at an early stage of pluripotency would therefore be ground-breaking in rendering this a practical and cost-effective approach to personalized medicine. Temporal information about changes in cellular appearance over time is crucial for predicting its future growth outcomes. In order to generate this data, we first performed continuous time-lapse imaging of iPSCs in culture using an ultra-high resolution microscope. We then annotated the locations and identities of cells in late-stage images where reliable manual identification is possible. Next, we propagated these labels backwards in time using a semi-automated tracking system to obtain labels for early stages of growth. Finally, we used this data to train deep neural networks to perform automatic cell segmentation and classification. Our code and data are available at https://github.com/abhineet123/ipsc_prediction.

Persistent homology (PH) provides topological descriptors for geometric data, such as weighted graphs, which are interpretable, stable to perturbations, and invariant under, e.g., relabeling. Most applications of PH focus on the one-parameter case -- where the descriptors summarize the changes in topology of data as it is filtered by a single quantity of interest -- and there is now a wide array of methods enabling the use of one-parameter PH descriptors in data science, which rely on the stable vectorization of these descriptors as elements of a Hilbert space. Although the multiparameter PH (MPH) of data that is filtered by several quantities of interest encodes much richer information than its one-parameter counterpart, the scarceness of stability results for MPH descriptors has so far limited the available options for the stable vectorization of MPH. In this paper, we aim to bring together the best of both worlds by showing how the interpretation of signed barcodes -- a recent family of MPH descriptors -- as signed measures leads to natural extensions of vectorization strategies from one parameter to multiple parameters. The resulting feature vectors are easy to define and to compute, and provably stable. While, as a proof of concept, we focus on simple choices of signed barcodes and vectorizations, we already see notable performance improvements when comparing our feature vectors to state-of-the-art topology-based methods on various types of data.

Modern representation learning increasingly relies on unsupervised and self-supervised methods trained on large-scale unlabeled data. While these approaches achieve impressive generalization across tasks and domains, evaluating embedding quality without labels remains an open challenge. In this work, we propose Persistence, a topology-aware metric based on persistent homology that quantifies the geometric structure and topological richness of embedding spaces in a fully unsupervised manner. Unlike metrics that assume linear separability or rely on covariance structure, Persistence captures global and multi-scale organization. Empirical results across diverse domains show that Persistence consistently achieves top-tier correlations with downstream performance, outperforming existing unsupervised metrics and enabling reliable model and hyperparameter selection.

For many segmentation tasks, especially for the biomedical image, the topological prior is vital information which is useful to exploit. The containment/nesting is a typical inter-class geometric relationship. In the MICCAI Brain tumor segmentation challenge, with its three hierarchically nested classes 'whole tumor', 'tumor core', 'active tumor', the nested classes relationship is introduced into the 3D-residual-Unet architecture. The network comprises a context aggregation pathway and a localization pathway, which encodes increasingly abstract representation of the input as going deeper into the network, and then recombines these representations with shallower features to precisely localize the interest domain via a localization path. The nested-class-prior is combined by proposing the multi-class activation function and its corresponding loss function. The model is trained on the training dataset of Brats2018, and 20% of the dataset is regarded as the validation dataset to determine parameters. When the parameters are fixed, we retrain the model on the whole training dataset. The performance achieved on the validation leaderboard is 86%, 77% and 72% Dice scores for the whole tumor, enhancing tumor and tumor core classes without relying on ensembles or complicated post-processing steps. Based on the same start-of-the-art network architecture, the accuracy of nested-class (enhancing tumor) is reasonably improved from 69% to 72% compared with the traditional Softmax-based method which blind to topological prior.

We algorithmically determine the regions and facets of all dimensions of the canonical polyhedral complex, the universal object into which a ReLU network decomposes its input space. We show that the locations of the vertices of the canonical polyhedral complex along with their signs with respect to layer maps determine the full facet structure across all dimensions. We present an algorithm which calculates this full combinatorial structure, making use of our theorems that the dual complex to the canonical polyhedral complex is cubical and it possesses a multiplication compatible with its facet structure. The resulting algorithm is numerically stable, polynomial time in the number of intermediate neurons, and obtains accurate information across all dimensions. This permits us to obtain, for example, the true topology of the decision boundaries of networks with low-dimensional inputs. We run empirics on such networks at initialization, finding that width alone does not increase observed topology, but width in the presence of depth does. Source code for our algorithms is accessible online at https://github.com/mmasden/canonicalpoly.

Complex prediction models such as deep learning are the output from fitting machine learning, neural networks, or AI models to a set of training data. These are now standard tools in science. A key challenge with the current generation of models is that they are highly parameterized, which makes describing and interpreting the prediction strategies difficult. We use topological data analysis to transform these complex prediction models into pictures representing a topological view. The result is a map of the predictions that enables inspection. The methods scale up to large datasets across different domains and enable us to detect labeling errors in training data, understand generalization in image classification, and inspect predictions of likely pathogenic mutations in the BRCA1 gene.

We present TopoMortar, a brick wall dataset that is the first dataset specifically designed to evaluate topology-focused image segmentation methods, such as topology loss functions. TopoMortar enables to investigate in two ways whether methods incorporate prior topological knowledge. First, by eliminating challenges seen in real-world data, such as small training set, noisy labels, and out-of-distribution test-set images, that, as we show, impact the effectiveness of topology losses. Second, by allowing to assess in the same dataset topology accuracy across dataset challenges, isolating dataset-related effects from the effect of incorporating prior topological knowledge. In these two experiments, it is deliberately difficult to improve topology accuracy without actually using topology information, thus, permitting to attribute an improvement in topology accuracy to the incorporation of prior topological knowledge. To this end, TopoMortar includes three types of labels (accurate, noisy, pseudo-labels), two fixed training sets (large and small), and in-distribution and out-of-distribution test-set images. We compared eight loss functions on TopoMortar, and we found that clDice achieved the most topologically accurate segmentations, Skeleton Recall loss performed best particularly with noisy labels, and the relative advantageousness of the other loss functions depended on the experimental setting. Additionally, we show that simple methods, such as data augmentation and self-distillation, can elevate Cross entropy Dice loss to surpass most topology loss functions, and that those simple methods can enhance topology loss functions as well. clDice and Skeleton Recall loss, both skeletonization-based loss functions, were also the fastest to train, making this type of loss function a promising research direction. TopoMortar and our code can be found at https://github.com/jmlipman/TopoMortar

In this paper we introduce a novel family of attributed graphs for the purpose of shape discrimination. Our graphs typically arise from variations on the Mapper graph construction, which is an approximation of the Reeb graph for point cloud data. Our attributions enrich these constructions with (persistent) homology in ways that are provably stable, thereby recording extra topological information that is typically lost in these graph constructions. We provide experiments which illustrate the use of these invariants for shape representation and classification. In particular, we obtain competitive shape classification results when using our topologically attributed graphs as inputs to a simple graph neural network classifier.

The segmentation of cell nuclei in tissue images stained with the blood dye hematoxylin and eosin (H&E) is essential for various clinical applications and analyses. Due to the complex characteristics of cellular morphology, a large receptive field is considered crucial for generating high-quality segmentation. However, previous methods face challenges in achieving a balance between the receptive field and computational burden. To address this issue, we propose LKCell, a high-accuracy and efficient cell segmentation method. Its core insight lies in unleashing the potential of large convolution kernels to achieve computationally efficient large receptive fields. Specifically, (1) We transfer pre-trained large convolution kernel models to the medical domain for the first time, demonstrating their effectiveness in cell segmentation. (2) We analyze the redundancy of previous methods and design a new segmentation decoder based on large convolution kernels. It achieves higher performance while significantly reducing the number of parameters. We evaluate our method on the most challenging benchmark and achieve state-of-the-art results (0.5080 mPQ) in cell nuclei instance segmentation with only 21.6% FLOPs compared with the previous leading method. Our source code and models are available at https://github.com/hustvl/LKCell.

High-content screening (HCS) assays based on high-throughput microscopy techniques such as Cell Painting have enabled the interrogation of cells' morphological responses to perturbations at an unprecedented scale. The collection of such data promises to facilitate a better understanding of the relationships between different perturbations and their effects on cellular state. Towards achieving this goal, recent advances in cross-modal contrastive learning could, in theory, be leveraged to learn a unified latent space that aligns perturbations with their corresponding morphological effects. However, the application of such methods to HCS data is not straightforward due to substantial differences in the semantics of Cell Painting images compared to natural images, and the difficulty of representing different classes of perturbations (e.g., small molecule vs CRISPR gene knockout) in a single latent space. In response to these challenges, here we introduce CellCLIP, a cross-modal contrastive learning framework for HCS data. CellCLIP leverages pre-trained image encoders coupled with a novel channel encoding scheme to better capture relationships between different microscopy channels in image embeddings, along with natural language encoders for representing perturbations. Our framework outperforms current open-source models, demonstrating the best performance in both cross-modal retrieval and biologically meaningful downstream tasks while also achieving significant reductions in computation time.

Image segmentation is a largely researched field where neural networks find vast applications in many facets of technology. Some of the most popular approaches to train segmentation networks employ loss functions optimizing pixel-overlap, an objective that is insufficient for many segmentation tasks. In recent years, their limitations fueled a growing interest in topology-aware methods, which aim to recover the correct topology of the segmented structures. However, so far, none of the existing approaches achieve a spatially correct matching between the topological features of ground truth and prediction. In this work, we propose the first topologically and feature-wise accurate metric and loss function for supervised image segmentation, which we term Betti matching. We show how induced matchings guarantee the spatially correct matching between barcodes in a segmentation setting. Furthermore, we propose an efficient algorithm to compute the Betti matching of images. We show that the Betti matching error is an interpretable metric to evaluate the topological correctness of segmentations, which is more sensitive than the well-established Betti number error. Moreover, the differentiability of the Betti matching loss enables its use as a loss function. It improves the topological performance of segmentation networks across six diverse datasets while preserving the volumetric performance. Our code is available in https://github.com/nstucki/Betti-matching.

Separating and labeling each instance of a nucleus (instance-aware segmentation) is the key challenge in segmenting single cell nuclei on fluorescence microscopy images. Deep Neural Networks can learn the implicit transformation of a nuclear image into a probability map indicating the class membership of each pixel (nucleus or background), but the use of post-processing steps to turn the probability map into a labeled object mask is error-prone. This especially accounts for nuclear images of tissue sections and nuclear images across varying tissue preparations. In this work, we aim to evaluate the performance of state-of-the-art deep learning architectures to segment nuclei in fluorescence images of various tissue origins and sample preparation types without post-processing. We compare architectures that operate on pixel to pixel translation and an architecture that operates on object detection and subsequent locally applied segmentation. In addition, we propose a novel strategy to create artificial images to extend the training set. We evaluate the influence of ground truth annotation quality, image scale and segmentation complexity on segmentation performance. Results show that three out of four deep learning architectures (U-Net, U-Net with ResNet34 backbone, Mask R-CNN) can segment fluorescent nuclear images on most of the sample preparation types and tissue origins with satisfactory segmentation performance. Mask R-CNN, an architecture designed to address instance aware segmentation tasks, outperforms other architectures. Equal nuclear mean size, consistent nuclear annotations and the use of artificially generated images result in overall acceptable precision and recall across different tissues and sample preparation types.

Large-scale cell microscopy screens are used in drug discovery and molecular biology research to study the effects of millions of chemical and genetic perturbations on cells. To use these images in downstream analysis, we need models that can map each image into a feature space that represents diverse biological phenotypes consistently, in the sense that perturbations with similar biological effects have similar representations. In this work, we present the largest foundation model for cell microscopy data to date, a new 1.9 billion-parameter ViT-G/8 MAE trained on over 8 billion microscopy image crops. Compared to a previous published ViT-L/8 MAE, our new model achieves a 60% improvement in linear separability of genetic perturbations and obtains the best overall performance on whole-genome biological relationship recall and replicate consistency benchmarks. Beyond scaling, we developed two key methods that improve performance: (1) training on a curated and diverse dataset; and, (2) using biologically motivated linear probing tasks to search across each transformer block for the best candidate representation of whole-genome screens. We find that many self-supervised vision transformers, pretrained on either natural or microscopy images, yield significantly more biologically meaningful representations of microscopy images in their intermediate blocks than in their typically used final blocks. More broadly, our approach and results provide insights toward a general strategy for successfully building foundation models for large-scale biological data.

Cell painting is a popular technique for creating human-interpretable, high-contrast images of cell morphology. There are two major issues with cell paint: (1) it is labor-intensive and (2) it requires chemical fixation, making the study of cell dynamics impossible. We train a diffusion model (Morphological Observation Neural Enhancement Tool, or MONET) on a large dataset to predict cell paint channels from brightfield images. We show that model quality improves with scale. The model uses a consistency architecture to generate time-lapse videos, despite the impossibility of obtaining cell paint video training data. In addition, we show that this architecture enables a form of in-context learning, allowing the model to partially transfer to out-of-distribution cell lines and imaging protocols. Virtual cell painting is not intended to replace physical cell painting completely, but to act as a complementary tool enabling novel workflows in biological research.

Although the preservation of shape continuity and physiological anatomy is a natural assumption in the segmentation of medical images, it is often neglected by deep learning methods that mostly aim for the statistical modeling of input data as pixels rather than interconnected structures. In biological structures, however, organs are not separate entities; for example, in reality, a severed vessel is an indication of an underlying problem, but traditional segmentation models are not designed to strictly enforce the continuity of anatomy, potentially leading to inaccurate medical diagnoses. To address this issue, we propose a graph-based approach that enforces the continuity and connectivity of anatomical topology in medical images. Our method encodes the continuity of shapes as a graph constraint, ensuring that the network's predictions maintain this continuity. We evaluate our method on two public benchmarks on retinal vessel segmentation, showing significant improvements in connectivity metrics compared to traditional methods while getting better or on-par performance on segmentation metrics.

This paper presents a Patherea, a framework for point-based cell detection and classification that provides a complete solution for developing and evaluating state-of-the-art approaches. We introduce a large-scale dataset collected to directly replicate a clinical workflow for Ki-67 proliferation index estimation and use it to develop an efficient point-based approach that directly predicts point-based predictions, without the need for intermediate representations. The proposed approach effectively utilizes point proposal candidates with the hybrid Hungarian matching strategy and a flexible architecture that enables the usage of various backbones and (pre)training strategies. We report state-of-the-art results on existing public datasets - Lizard, BRCA-M2C, BCData, and the newly proposed Patherea dataset. We show that the performance on existing public datasets is saturated and that the newly proposed Patherea dataset represents a significantly harder challenge for the recently proposed approaches. We also demonstrate the effectiveness of recently proposed pathology foundational models that our proposed approach can natively utilize and benefit from. We also revisit the evaluation protocol that is used in the broader field of cell detection and classification and identify the erroneous calculation of performance metrics. Patherea provides a benchmarking utility that addresses the identified issues and enables a fair comparison of different approaches. The dataset and the code will be publicly released upon acceptance.

Biological neural networks define the brain function and intelligence of humans and other mammals, and form ultra-large, spatial, structured graphs. Their neuronal organization is closely interconnected with the spatial organization of the brain's microvasculature, which supplies oxygen to the neurons and builds a complementary spatial graph. This vasculature (or the vessel structure) plays an important role in neuroscience; for example, the organization of (and changes to) vessel structure can represent early signs of various pathologies, e.g. Alzheimer's disease or stroke. Recently, advances in tissue clearing have enabled whole brain imaging and segmentation of the entirety of the mouse brain's vasculature. Building on these advances in imaging, we are presenting an extendable dataset of whole-brain vessel graphs based on specific imaging protocols. Specifically, we extract vascular graphs using a refined graph extraction scheme leveraging the volume rendering engine Voreen and provide them in an accessible and adaptable form through the OGB and PyTorch Geometric dataloaders. Moreover, we benchmark numerous state-of-the-art graph learning algorithms on the biologically relevant tasks of vessel prediction and vessel classification using the introduced vessel graph dataset. Our work paves a path towards advancing graph learning research into the field of neuroscience. Complementarily, the presented dataset raises challenging graph learning research questions for the machine learning community, in terms of incorporating biological priors into learning algorithms, or in scaling these algorithms to handle sparse,spatial graphs with millions of nodes and edges. All datasets and code are available for download at https://github.com/jocpae/VesselGraph .

Instance segmentation is critical in biomedical imaging to accurately distinguish individual objects like cells, which often overlap and vary in size. Recent query-based methods, where object queries guide segmentation, have shown strong performance. While U-Net has been a go-to architecture in medical image segmentation, its potential in query-based approaches remains largely unexplored. In this work, we present IAUNet, a novel query-based U-Net architecture. The core design features a full U-Net architecture, enhanced by a novel lightweight convolutional Pixel decoder, making the model more efficient and reducing the number of parameters. Additionally, we propose a Transformer decoder that refines object-specific features across multiple scales. Finally, we introduce the 2025 Revvity Full Cell Segmentation Dataset, a unique resource with detailed annotations of overlapping cell cytoplasm in brightfield images, setting a new benchmark for biomedical instance segmentation. Experiments on multiple public datasets and our own show that IAUNet outperforms most state-of-the-art fully convolutional, transformer-based, and query-based models and cell segmentation-specific models, setting a strong baseline for cell instance segmentation tasks. Code is available at https://github.com/SlavkoPrytula/IAUNet

Accurate segmentation of topological tubular structures, such as blood vessels and roads, is crucial in various fields, ensuring accuracy and efficiency in downstream tasks. However, many factors complicate the task, including thin local structures and variable global morphologies. In this work, we note the specificity of tubular structures and use this knowledge to guide our DSCNet to simultaneously enhance perception in three stages: feature extraction, feature fusion, and loss constraint. First, we propose a dynamic snake convolution to accurately capture the features of tubular structures by adaptively focusing on slender and tortuous local structures. Subsequently, we propose a multi-view feature fusion strategy to complement the attention to features from multiple perspectives during feature fusion, ensuring the retention of important information from different global morphologies. Finally, a continuity constraint loss function, based on persistent homology, is proposed to constrain the topological continuity of the segmentation better. Experiments on 2D and 3D datasets show that our DSCNet provides better accuracy and continuity on the tubular structure segmentation task compared with several methods. Our codes will be publicly available.

The manifold hypothesis, which assumes that data lies on or close to an unknown manifold of low intrinsic dimension, is a staple of modern machine learning research. However, recent work has shown that real-world data exhibits distinct non-manifold structures, i.e. singularities, that can lead to erroneous findings. Detecting such singularities is therefore crucial as a precursor to interpolation and inference tasks. We address this issue by developing a topological framework that (i) quantifies the local intrinsic dimension, and (ii) yields a Euclidicity score for assessing the 'manifoldness' of a point along multiple scales. Our approach identifies singularities of complex spaces, while also capturing singular structures and local geometric complexity in image data.

Cell type annotation is a key task in analyzing the heterogeneity of single-cell RNA sequencing data. Although recent foundation models automate this process, they typically annotate cells independently, without considering batch-level cellular context or providing explanatory reasoning. In contrast, human experts often annotate distinct cell types for different cell clusters based on their domain knowledge. To mimic this workflow, we introduce the CellPuzzles task, where the objective is to assign unique cell types to a batch of cells. This benchmark spans diverse tissues, diseases, and donor conditions, and requires reasoning across the batch-level cellular context to ensure label uniqueness. We find that off-the-shelf large language models (LLMs) struggle on CellPuzzles, with the best baseline (OpenAI's o1) achieving only 19.0% batch-level accuracy. To fill this gap, we propose Cell-o1, a 7B LLM trained via supervised fine-tuning on distilled reasoning traces, followed by reinforcement learning with batch-level rewards. Cell-o1 achieves state-of-the-art performance, outperforming o1 by over 73% and generalizing well across contexts. Further analysis of training dynamics and reasoning behaviors provides insights into batch-level annotation performance and emergent expert-like reasoning. Code and data are available at https://github.com/ncbi-nlp/cell-o1.

Cell segmentation is a critical step for quantitative single-cell analysis in microscopy images. Existing cell segmentation methods are often tailored to specific modalities or require manual interventions to specify hyperparameters in different experimental settings. Here, we present a multi-modality cell segmentation benchmark, comprising over 1500 labeled images derived from more than 50 diverse biological experiments. The top participants developed a Transformer-based deep-learning algorithm that not only exceeds existing methods, but can also be applied to diverse microscopy images across imaging platforms and tissue types without manual parameter adjustments. This benchmark and the improved algorithm offer promising avenues for more accurate and versatile cell analysis in microscopy imaging.

Instance segmentation of neurons in volumetric light microscopy images of nervous systems enables groundbreaking research in neuroscience by facilitating joint functional and morphological analyses of neural circuits at cellular resolution. Yet said multi-neuron light microscopy data exhibits extremely challenging properties for the task of instance segmentation: Individual neurons have long-ranging, thin filamentous and widely branching morphologies, multiple neurons are tightly inter-weaved, and partial volume effects, uneven illumination and noise inherent to light microscopy severely impede local disentangling as well as long-range tracing of individual neurons. These properties reflect a current key challenge in machine learning research, namely to effectively capture long-range dependencies in the data. While respective methodological research is buzzing, to date methods are typically benchmarked on synthetic datasets. To address this gap, we release the FlyLight Instance Segmentation Benchmark (FISBe) dataset, the first publicly available multi-neuron light microscopy dataset with pixel-wise annotations. In addition, we define a set of instance segmentation metrics for benchmarking that we designed to be meaningful with regard to downstream analyses. Lastly, we provide three baselines to kick off a competition that we envision to both advance the field of machine learning regarding methodology for capturing long-range data dependencies, and facilitate scientific discovery in basic neuroscience.

Identifying cell types and understanding their functional properties is crucial for unraveling the mechanisms underlying perception and cognition. In the retina, functional types can be identified by carefully selected stimuli, but this requires expert domain knowledge and biases the procedure towards previously known cell types. In the visual cortex, it is still unknown what functional types exist and how to identify them. Thus, for unbiased identification of the functional cell types in retina and visual cortex, new approaches are needed. Here we propose an optimization-based clustering approach using deep predictive models to obtain functional clusters of neurons using Most Discriminative Stimuli (MDS). Our approach alternates between stimulus optimization with cluster reassignment akin to an expectation-maximization algorithm. The algorithm recovers functional clusters in mouse retina, marmoset retina and macaque visual area V4. This demonstrates that our approach can successfully find discriminative stimuli across species, stages of the visual system and recording techniques. The resulting most discriminative stimuli can be used to assign functional cell types fast and on the fly, without the need to train complex predictive models or show a large natural scene dataset, paving the way for experiments that were previously limited by experimental time. Crucially, MDS are interpretable: they visualize the distinctive stimulus patterns that most unambiguously identify a specific type of neuron.

In hematology, computational models offer significant potential to improve diagnostic accuracy, streamline workflows, and reduce the tedious work of analyzing single cells in peripheral blood or bone marrow smears. However, clinical adoption of computational models has been hampered by the lack of generalization due to large batch effects, small dataset sizes, and poor performance in transfer learning from natural images. To address these challenges, we introduce DinoBloom, the first foundation model for single cell images in hematology, utilizing a tailored DINOv2 pipeline. Our model is built upon an extensive collection of 13 diverse, publicly available datasets of peripheral blood and bone marrow smears, the most substantial open-source cohort in hematology so far, comprising over 380,000 white blood cell images. To assess its generalization capability, we evaluate it on an external dataset with a challenging domain shift. We show that our model outperforms existing medical and non-medical vision models in (i) linear probing and k-nearest neighbor evaluations for cell-type classification on blood and bone marrow smears and (ii) weakly supervised multiple instance learning for acute myeloid leukemia subtyping by a large margin. A family of four DinoBloom models (small, base, large, and giant) can be adapted for a wide range of downstream applications, be a strong baseline for classification problems, and facilitate the assessment of batch effects in new datasets. All models are available at github.com/marrlab/DinoBloom.

Nuclear segmentation, classification and quantification within Haematoxylin & Eosin stained histology images enables the extraction of interpretable cell-based features that can be used in downstream explainable models in computational pathology (CPath). However, automatic recognition of different nuclei is faced with a major challenge in that there are several different types of nuclei, some of them exhibiting large intraclass variability. In this work, we propose an approach that combine Separable-HoverNet and Instance-YOLOv5 to indentify colon nuclei small and unbalanced. Our approach can achieve mPQ+ 0.389 on the Segmentation and Classification-Preliminary Test Dataset and r2 0.599 on the Cellular Composition-Preliminary Test Dataset on ISBI 2022 CoNIC Challenge.

We present a new table structure recognition (TSR) approach, called TSRFormer, to robustly recognizing the structures of complex tables with geometrical distortions from various table images. Unlike previous methods, we formulate table separation line prediction as a line regression problem instead of an image segmentation problem and propose a new two-stage DETR based separator prediction approach, dubbed Separator REgression TRansformer (SepRETR), to predict separation lines from table images directly. To make the two-stage DETR framework work efficiently and effectively for the separation line prediction task, we propose two improvements: 1) A prior-enhanced matching strategy to solve the slow convergence issue of DETR; 2) A new cross attention module to sample features from a high-resolution convolutional feature map directly so that high localization accuracy is achieved with low computational cost. After separation line prediction, a simple relation network based cell merging module is used to recover spanning cells. With these new techniques, our TSRFormer achieves state-of-the-art performance on several benchmark datasets, including SciTSR, PubTabNet and WTW. Furthermore, we have validated the robustness of our approach to tables with complex structures, borderless cells, large blank spaces, empty or spanning cells as well as distorted or even curved shapes on a more challenging real-world in-house dataset.

In recent years, persistent homology (PH) has been successfully applied to real-world data in many different settings. Despite significant computational advances, PH algorithms do not yet scale to large datasets preventing interesting applications. One approach to address computational issues posed by PH is to select a set of landmarks by subsampling from the data. Currently, these landmark points are chosen either at random or using the maxmin algorithm. Neither is ideal as random selection tends to favour dense areas of the data while the maxmin algorithm is very sensitive to noise. Here, we propose a novel approach to select landmarks specifically for PH that preserves coarse topological information of the original dataset. Our method is motivated by the Mayer-Vietoris sequence and requires only local PH computation thus enabling efficient computation. We test our landmarks on artificial datasets which contain different levels of noise and compare them to standard landmark selection techniques. We demonstrate that our landmark selection outperforms standard methods as well as a subsampling technique based on an outlier-robust version of the k--means algorithm for low sampling densities in noisy data with respect to robustness to outliers.

Image-based 3D reconstruction has increasingly stunning results over the past few years with the latest improvements in computer vision and graphics. Geometry and topology are two fundamental concepts when dealing with 3D mesh structures. But the latest often remains a side issue in the 3D mesh-based reconstruction literature. Indeed, performing per-vertex elementary displacements over a 3D sphere mesh only impacts its geometry and leaves the topological structure unchanged and fixed. Whereas few attempts propose to update the geometry and the topology, all need to lean on costly 3D ground-truth to determine the faces/edges to prune. We present in this work a method that aims to refine the topology of any 3D mesh through a face-pruning strategy that extensively relies upon 2D alpha masks and camera pose information. Our solution leverages a differentiable renderer that renders each face as a 2D soft map. Its pixel intensity reflects the probability of being covered during the rendering process by such a face. Based on the 2D soft-masks available, our method is thus able to quickly highlight all the incorrectly rendered faces for a given viewpoint. Because our module is agnostic to the network that produces the 3D mesh, it can be easily plugged into any self-supervised image-based (either synthetic or natural) 3D reconstruction pipeline to get complex meshes with a non-spherical topology.

Object recognition plays a fundamental role in how biological organisms perceive and interact with their environment. While the human visual system performs this task with remarkable efficiency, reproducing similar capabilities in artificial systems remains challenging. This study investigates VisNet, a biologically inspired neural network model, and several enhanced variants incorporating radial basis function neurons, Mahalanobis distance based learning, and retinal like preprocessing for both general object recognition and symmetry classification. By leveraging principles of Hebbian learning and temporal continuity associating temporally adjacent views to build invariant representations. VisNet and its extensions capture robust and transformation invariant features. Experimental results across multiple datasets, including MNIST, CIFAR10, and custom symmetric object sets, show that these enhanced VisNet variants substantially improve recognition accuracy compared with the baseline model. These findings underscore the adaptability and biological relevance of VisNet inspired architectures, offering a powerful and interpretable framework for visual recognition in both neuroscience and artificial intelligence. Keywords: VisNet, Object Recognition, Symmetry Detection, Hebbian Learning, RBF Neurons, Mahalanobis Distance, Biologically Inspired Models, Invariant Representations

Self-supervised vision models have achieved notable success in digital pathology. However, their domain-agnostic transformer architectures are not originally designed to account for fundamental biological elements of histopathology images, namely cells and their complex interactions. In this work, we hypothesize that a biologically-informed modeling of tissues as cell graphs offers a more efficient representation learning. Thus, we introduce GrapHist, a novel graph-based self-supervised learning framework for histopathology, which learns generalizable and structurally-informed embeddings that enable diverse downstream tasks. GrapHist integrates masked autoencoders and heterophilic graph neural networks that are explicitly designed to capture the heterogeneity of tumor microenvironments. We pre-train GrapHist on a large collection of 11 million cell graphs derived from breast tissues and evaluate its transferability across in- and out-of-domain benchmarks. Our results show that GrapHist achieves competitive performance compared to its vision-based counterparts in slide-, region-, and cell-level tasks, while requiring four times fewer parameters. It also drastically outperforms fully-supervised graph models on cancer subtyping tasks. Finally, we also release five graph-based digital pathology datasets used in our study at https://huggingface.co/ogutsevda/datasets , establishing the first large-scale graph benchmark in this field. Our code is available at https://github.com/ogutsevda/graphist .

Quantifying cell morphology using images and machine learning has proven to be a powerful tool to study the response of cells to treatments. However, models used to quantify cellular morphology are typically trained with a single microscopy imaging type. This results in specialized models that cannot be reused across biological studies because the technical specifications do not match (e.g., different number of channels), or because the target experimental conditions are out of distribution. Here, we present CHAMMI-75, an open access dataset of heterogeneous, multi-channel microscopy images from 75 diverse biological studies. We curated this resource from publicly available sources to investigate cellular morphology models that are channel-adaptive and can process any microscopy image type. Our experiments show that training with CHAMMI-75 can improve performance in multi-channel bioimaging tasks primarily because of its high diversity in microscopy modalities. This work paves the way to create the next generation of cellular morphology models for biological studies.

With the advent of novel cancer treatment options such as immunotherapy, studying the tumour immune micro-environment (TIME) is crucial to inform on prognosis and understand potential response to therapeutic agents. A key approach to characterising the TIME may be through combining (1) digitised microscopic high-resolution optical images of hematoxylin and eosin (H&E) stained tissue sections obtained in routine histopathology examinations with (2) automated immune cell detection and classification methods. In this work, we introduce a workflow to automatically generate robust single cell contours and labels from dually stained tissue sections with H&E and multiplexed immunofluorescence (IF) markers. The approach harnesses the Segment Anything Model and requires minimal human intervention compared to existing single cell databases. With this methodology, we create Immunocto, a massive, multi-million automatically generated database of 6,848,454 human cells and objects, including 2,282,818 immune cells distributed across 4 subtypes: CD4^+ T cell lymphocytes, CD8^+ T cell lymphocytes, CD20^+ B cell lymphocytes, and CD68^+/CD163^+ macrophages. For each cell, we provide a 64times64 pixels^2 H&E image at 40times magnification, along with a binary mask of the nucleus and a label. The database, which is made publicly available, can be used to train models to study the TIME on routine H&E slides. We show that deep learning models trained on Immunocto result in state-of-the-art performance for lymphocyte detection. The approach demonstrates the benefits of using matched H&E and IF data to generate robust databases for computational pathology applications.

The rapidly growing field of single-cell transcriptomic sequencing (scRNAseq) presents challenges for data analysis due to its massive datasets. A common method in manifold learning consists in hypothesizing that datasets lie on a lower dimensional manifold. This allows to study the geometry of point clouds by extracting meaningful descriptors like curvature. In this work, we will present Adaptive Local PCA (AdaL-PCA), a data-driven method for accurately estimating various notions of intrinsic curvature on data manifolds, in particular principal curvatures for surfaces. The model relies on local PCA to estimate the tangent spaces. The evaluation of AdaL-PCA on sampled surfaces shows state-of-the-art results. Combined with a PHATE embedding, the model applied to single-cell RNA sequencing data allows us to identify key variations in the cellular differentiation.

We report DynaCLR, a self-supervised method for embedding cell and organelle Dynamics via Contrastive Learning of Representations of time-lapse images. DynaCLR integrates single-cell tracking and time-aware contrastive sampling to learn robust, temporally regularized representations of cell dynamics. DynaCLR embeddings generalize effectively to in-distribution and out-of-distribution datasets, and can be used for several downstream tasks with sparse human annotations. We demonstrate efficient annotations of cell states with a human-in-the-loop using fluorescence and label-free imaging channels. DynaCLR method enables diverse downstream biological analyses: classification of cell division and infection, clustering heterogeneous cell migration patterns, cross-modal distillation of cell states from fluorescence to label-free channel, alignment of asynchronous cellular responses and broken cell tracks, and discovering organelle response due to infection. DynaCLR is a flexible method for comparative analyses of dynamic cellular responses to pharmacological, microbial, and genetic perturbations. We provide PyTorch-based implementations of the model training and inference pipeline (https://github.com/mehta-lab/viscy) and a GUI (https://github.com/czbiohub-sf/napari-iohub) for the visualization and annotation of trajectories of cells in the real space and the embedding space.

The task of table structure recognition aims to recognize the internal structure of a table, which is a key step to make machines understand tables. Currently, there are lots of studies on this task for different file formats such as ASCII text and HTML. It also attracts lots of attention to recognize the table structures in PDF files. However, it is hard for the existing methods to accurately recognize the structure of complicated tables in PDF files. The complicated tables contain spanning cells which occupy at least two columns or rows. To address the issue, we propose a novel graph neural network for recognizing the table structure in PDF files, named GraphTSR. Specifically, it takes table cells as input, and then recognizes the table structures by predicting relations among cells. Moreover, to evaluate the task better, we construct a large-scale table structure recognition dataset from scientific papers, named SciTSR, which contains 15,000 tables from PDF files and their corresponding structure labels. Extensive experiments demonstrate that our proposed model is highly effective for complicated tables and outperforms state-of-the-art baselines over a benchmark dataset and our new constructed dataset.

Computational pathology relies on effective representation learning to support cancer research and precision medicine. Although self-supervised learning has driven major progress at the patch and whole-slide image levels, representation learning at the single-cell level remains comparatively underexplored, despite its importance for characterizing cell types and cellular phenotypes. We introduce LEMON (Learning Embeddings from Morphology Of Nuclei), a self-supervised foundation model for scalable single-cell image representation learning. Trained on millions of cell images from diverse tissues and cancer types, LEMON learns robust and versatile morphological representations that support large-scale single-cell analyses in pathology. We evaluate LEMON on five benchmark datasets across a range of prediction tasks and show that it provides strong performance, highlighting its potential as a new paradigm for cell-level computational pathology. Model weights are available at https://huggingface.co/aliceblondel/LEMON.

Histopathological analysis is a cornerstone of cancer diagnosis, with Hematoxylin and Eosin (H&E) staining routinely acquired for every patient to visualize cell morphology and tissue architecture. On the other hand, multiplex immunofluorescence (mIF) enables more precise cell type identification via proteomic markers, but has yet to achieve widespread clinical adoption due to cost and logistical constraints. To bridge this gap, we introduce MIPHEI (Multiplex Immunofluorescence Prediction from H&E), a U-Net-inspired architecture that integrates state-of-the-art ViT foundation models as encoders to predict mIF signals from H&E images. MIPHEI targets a comprehensive panel of markers spanning nuclear content, immune lineages (T cells, B cells, myeloid), epithelium, stroma, vasculature, and proliferation. We train our model using the publicly available ORION dataset of restained H&E and mIF images from colorectal cancer tissue, and validate it on two independent datasets. MIPHEI achieves accurate cell-type classification from H&E alone, with F1 scores of 0.88 for Pan-CK, 0.57 for CD3e, 0.56 for SMA, 0.36 for CD68, and 0.30 for CD20, substantially outperforming both a state-of-the-art baseline and a random classifier for most markers. Our results indicate that our model effectively captures the complex relationships between nuclear morphologies in their tissue context, as visible in H&E images and molecular markers defining specific cell types. MIPHEI offers a promising step toward enabling cell-type-aware analysis of large-scale H&E datasets, in view of uncovering relationships between spatial cellular organization and patient outcomes.

The natural world is full of complex systems characterized by intricate relations between their components: from social interactions between individuals in a social network to electrostatic interactions between atoms in a protein. Topological Deep Learning (TDL) provides a comprehensive framework to process and extract knowledge from data associated with these systems, such as predicting the social community to which an individual belongs or predicting whether a protein can be a reasonable target for drug development. TDL has demonstrated theoretical and practical advantages that hold the promise of breaking ground in the applied sciences and beyond. However, the rapid growth of the TDL literature has also led to a lack of unification in notation and language across Topological Neural Network (TNN) architectures. This presents a real obstacle for building upon existing works and for deploying TNNs to new real-world problems. To address this issue, we provide an accessible introduction to TDL, and compare the recently published TNNs using a unified mathematical and graphical notation. Through an intuitive and critical review of the emerging field of TDL, we extract valuable insights into current challenges and exciting opportunities for future development.

Processing information on 3D objects requires methods stable to rigid-body transformations, in particular rotations, of the input data. In image processing tasks, convolutional neural networks achieve this property using rotation-equivariant operations. However, contrary to images, graphs generally have irregular topology. This makes it challenging to define a rotation-equivariant convolution operation on these structures. In this work, we propose Spherical Graph Convolutional Network (S-GCN) that processes 3D models of proteins represented as molecular graphs. In a protein molecule, individual amino acids have common topological elements. This allows us to unambiguously associate each amino acid with a local coordinate system and construct rotation-equivariant spherical filters that operate on angular information between graph nodes. Within the framework of the protein model quality assessment problem, we demonstrate that the proposed spherical convolution method significantly improves the quality of model assessment compared to the standard message-passing approach. It is also comparable to state-of-the-art methods, as we demonstrate on Critical Assessment of Structure Prediction (CASP) benchmarks. The proposed technique operates only on geometric features of protein 3D models. This makes it universal and applicable to any other geometric-learning task where the graph structure allows constructing local coordinate systems.

We propose a novel approach for preserving topological structures of the input space in latent representations of autoencoders. Using persistent homology, a technique from topological data analysis, we calculate topological signatures of both the input and latent space to derive a topological loss term. Under weak theoretical assumptions, we construct this loss in a differentiable manner, such that the encoding learns to retain multi-scale connectivity information. We show that our approach is theoretically well-founded and that it exhibits favourable latent representations on a synthetic manifold as well as on real-world image data sets, while preserving low reconstruction errors.

Manual peripheral blood smear (PBS) analysis is labor intensive and subjective. While deep learning offers a promising alternative, a systematic evaluation of state of the art models such as YOLOv11 for fine grained PBS detection is still lacking. In this work, we make two key contributions. First, we curate a large scale annotated dataset for blood cell detection and classification, comprising 16,891 images across 12 peripheral blood cell (PBC) classes, along with the red blood cell class, all carefully re annotated for object detection tasks. In total, the dataset contains 298,850 annotated cells. Second, we leverage this dataset to conduct a comprehensive evaluation of five YOLOv11 variants (ranging from Nano to XLarge). These models are rigorously benchmarked under two data splitting strategies (70:20:10 and 80:10:10) and systematically assessed using multiple performance criteria, including mean Average Precision (mAP), precision, recall, F1 score, and computational efficiency. Our experiments show that the YOLOv11 Medium variant achieves the best trade off, reaching a mAP@0.5 of 0.934 under the 8:1:1 split. Larger models (Large and XLarge) provide only marginal accuracy gains at substantially higher computational cost. Moreover, the 8:1:1 split consistently outperforms the 7:2:1 split across all models. These findings highlight YOLOv11, particularly the Medium variant, as a highly effective framework for automated, fine grained PBS detection. Beyond benchmarking, our publicly released dataset (github.com/Mohamad-AbouAli/OI-PBC-Dataset) offers a valuable resource to advance research on blood cell detection and classification in hematology.

Modeling medical vessel-like anatomy is challenging due to its intricate topology and sensitivity to dataset shifts. Consequently, task-specific models often suffer from topological inconsistencies, including artificial disconnections and spurious merges. Motivated by the promise of multimodal large language models (MLLMs) for zero-shot generalization, we propose TubeMLLM, a unified foundation model that couples structured understanding with controllable generation for medical vessel-like anatomy. By integrating topological priors through explicit natural language prompting and aligning them with visual representations in a shared-attention architecture, TubeMLLM significantly enhances topology-aware perception. Furthermore, we construct TubeMData, a pionner multimodal benchmark comprising comprehensive topology-centric tasks, and introduce an adaptive loss weighting strategy to emphasize topology-critical regions during training. Extensive experiments on fifteen diverse datasets demonstrate our superiority. Quantitatively, TubeMLLM achieves state-of-the-art out-of-distribution performance, substantially reducing global topological discrepancies on color fundus photography (decreasing the β_{0} number error from 37.42 to 8.58 compared to baselines). Notably, TubeMLLM exhibits exceptional zero-shot cross-modality transferring ability on unseen X-ray angiography, achieving a Dice score of 67.50% while significantly reducing the β_{0} error to 1.21. TubeMLLM also maintains robustness against degradations such as blur, noise, and low resolution. Furthermore, in topology-aware understanding tasks, the model achieves 97.38% accuracy in evaluating mask topological quality, significantly outperforming standard vision-language baselines.

There is a growing body of work that leverages features extracted via topological data analysis to train machine learning models. While this field, sometimes known as topological machine learning (TML), has seen some notable successes, an understanding of how the process of learning from topological features differs from the process of learning from raw data is still limited. In this work, we begin to address one component of this larger issue by asking whether a model trained with topological features learns internal representations of data that are fundamentally different than those learned by a model trained with the original raw data. To quantify ``different'', we exploit two popular metrics that can be used to measure the similarity of the hidden representations of data within neural networks, neural stitching and centered kernel alignment. From these we draw a range of conclusions about how training with topological features does and does not change the representations that a model learns. Perhaps unsurprisingly, we find that structurally, the hidden representations of models trained and evaluated on topological features differ substantially compared to those trained and evaluated on the corresponding raw data. On the other hand, our experiments show that in some cases, these representations can be reconciled (at least to the degree required to solve the corresponding task) using a simple affine transformation. We conjecture that this means that neural networks trained on raw data may extract some limited topological features in the process of making predictions.

Computer vision techniques have advanced significantly in recent years, finding diverse and impactful applications within the medical field. In this paper, we introduce a new framework for the detection of Bethesda cells in Pap smear images, developed for Track B of the Riva Cytology Challenge held in association with the International Symposium on Biomedical Imaging (ISBI). This work focuses on enhancing computer vision models for cell detection, with performance evaluated using the mAP50-95 metric. We propose a solution based on an ensemble of YOLO and U-Net architectures, followed by a refinement stage utilizing overlap removal techniques and a binary classifier. Our framework achieved second place with a mAP50-95 score of 0.5909 in the competition. The implementation and source code are available at the following repository: github.com/martinamster/riva-trackb

Cell instance segmentation is a fundamental task in digital pathology with broad clinical applications. Recently, vision foundation models, which are predominantly based on Vision Transformers (ViTs), have achieved remarkable success in pathology image analysis. However, their improvements in cell instance segmentation remain limited. A key challenge arises from the tokenization process in ViTs, which substantially reduces the spatial resolution of input images, leading to suboptimal segmentation quality, especially for small and densely packed cells. To address this problem, we propose CellVTA (Cell Vision Transformer with Adapter), a novel method that improves the performance of vision foundation models for cell instance segmentation by incorporating a CNN-based adapter module. This adapter extracts high-resolution spatial information from input images and injects it into the ViT through a cross-attention mechanism. Our method preserves the core architecture of ViT, ensuring seamless integration with pretrained foundation models. Extensive experiments show that CellVTA achieves 0.538 mPQ on the CoNIC dataset and 0.506 mPQ on the PanNuke dataset, which significantly outperforms the state-of-the-art cell segmentation methods. Ablation studies confirm the superiority of our approach over other fine-tuning strategies, including decoder-only fine-tuning and full fine-tuning. Our code and models are publicly available at https://github.com/JieZheng-ShanghaiTech/CellVTA.

Computational microscopy, in which hardware and algorithms of an imaging system are jointly designed, shows promise for making imaging systems that cost less, perform more robustly, and collect new types of information. Often, the performance of computational imaging systems, especially those that incorporate machine learning, is sample-dependent. Thus, standardized datasets are an essential tool for comparing the performance of different approaches. Here, we introduce the Berkeley Single Cell Computational Microscopy (BSCCM) dataset, which contains over ~12,000,000 images of 400,000 of individual white blood cells. The dataset contains images captured with multiple illumination patterns on an LED array microscope and fluorescent measurements of the abundance of surface proteins that mark different cell types. We hope this dataset will provide a valuable resource for the development and testing of new algorithms in computational microscopy and computer vision with practical biomedical applications.

Topological Neural Networks (TNNs) incorporate higher-order relational information beyond pairwise interactions, enabling richer representations than Graph Neural Networks (GNNs). Concurrently, topological descriptors based on persistent homology (PH) are being increasingly employed to augment the GNNs. We investigate the benefits of integrating these two paradigms. Specifically, we introduce TopNets as a broad framework that subsumes and unifies various methods in the intersection of GNNs/TNNs and PH such as (generalizations of) RePHINE and TOGL. TopNets can also be readily adapted to handle (symmetries in) geometric complexes, extending the scope of TNNs and PH to spatial settings. Theoretically, we show that PH descriptors can provably enhance the expressivity of simplicial message-passing networks. Empirically, (continuous and E(n)-equivariant extensions of) TopNets achieve strong performance across diverse tasks, including antibody design, molecular dynamics simulation, and drug property prediction.

Large language models (LLMs) are increasingly applied in scientific research, offering new capabilities for knowledge discovery and reasoning. In single-cell biology, however, evaluation practices for both general and specialized LLMs remain inadequate: existing benchmarks are fragmented across tasks, adopt formats such as multiple-choice classification that diverge from real-world usage, and rely on metrics lacking interpretability and biological grounding. We present SC-ARENA, a natural language evaluation framework tailored to single-cell foundation models. SC-ARENA formalizes a virtual cell abstraction that unifies evaluation targets by representing both intrinsic attributes and gene-level interactions. Within this paradigm, we define five natural language tasks (cell type annotation, captioning, generation, perturbation prediction, and scientific QA) that probe core reasoning capabilities in cellular biology. To overcome the limitations of brittle string-matching metrics, we introduce knowledge-augmented evaluation, which incorporates external ontologies, marker databases, and scientific literature to support biologically faithful and interpretable judgments. Experiments and analysis across both general-purpose and domain-specialized LLMs demonstrate that (i) under the Virtual Cell unified evaluation paradigm, current models achieve uneven performance on biologically complex tasks, particularly those demanding mechanistic or causal understanding; and (ii) our knowledge-augmented evaluation framework ensures biological correctness, provides interpretable, evidence-grounded rationales, and achieves high discriminative capacity, overcoming the brittleness and opacity of conventional metrics. SC-Arena thus provides a unified and interpretable framework for assessing LLMs in single-cell biology, pointing toward the development of biology-aligned, generalizable foundation models.

Star-convex shapes arise across bio-microscopy and radiology in the form of nuclei, nodules, metastases, and other units. Existing instance segmentation networks for such structures train on densely labeled instances for each dataset, which requires substantial and often impractical manual annotation effort. Further, significant reengineering or finetuning is needed when presented with new datasets and imaging modalities due to changes in contrast, shape, orientation, resolution, and density. We present AnyStar, a domain-randomized generative model that simulates synthetic training data of blob-like objects with randomized appearance, environments, and imaging physics to train general-purpose star-convex instance segmentation networks. As a result, networks trained using our generative model do not require annotated images from unseen datasets. A single network trained on our synthesized data accurately 3D segments C. elegans and P. dumerilii nuclei in fluorescence microscopy, mouse cortical nuclei in micro-CT, zebrafish brain nuclei in EM, and placental cotyledons in human fetal MRI, all without any retraining, finetuning, transfer learning, or domain adaptation. Code is available at https://github.com/neel-dey/AnyStar.

Multiplex immunofluorescence and immunohistochemistry benefit patients by allowing cancer pathologists to identify several proteins expressed on the surface of cells, enabling cell classification, better understanding of the tumour micro-environment, more accurate diagnoses, prognoses, and tailored immunotherapy based on the immune status of individual patients. However, they are expensive and time consuming processes which require complex staining and imaging techniques by expert technicians. Hoechst staining is much cheaper and easier to perform, but is not typically used in this case as it binds to DNA rather than to the proteins targeted by immunofluorescent techniques, and it was not previously thought possible to differentiate cells expressing these proteins based only on DNA morphology. In this work we show otherwise, training a deep convolutional neural network to identify cells expressing three proteins (T lymphocyte markers CD3 and CD8, and the B lymphocyte marker CD20) with greater than 90% precision and recall, from Hoechst 33342 stained tissue only. Our model learns previously unknown morphological features associated with expression of these proteins which can be used to accurately differentiate lymphocyte subtypes for use in key prognostic metrics such as assessment of immune cell infiltration,and thereby predict and improve patient outcomes without the need for costly multiplex immunofluorescence.

Cells that collide with each other repolarize away from contact, in a process called contact inhibition of locomotion (CIL), which is necessary for correct development of the embryo. CIL can occur even when cells make a micron-scale contact with a neighbor - much smaller than their size. How precisely can a cell sense cell-cell contact and repolarize in the correct direction? What factors control whether a cell recognizes it has contacted a neighbor? We propose a theoretical model for the limits of CIL where cells recognize the presence of another cell by binding the protein ephrin with the Eph receptor. This recognition is made difficult by the presence of interfering ligands that bind nonspecifically. Both theoretical predictions and simulation results show that it becomes more difficult to sense cell-cell contact when it is difficult to distinguish ephrin from the interfering ligands, or when there are more interfering ligands, or when the contact width decreases. However, the error of estimating contact position remains almost constant when the contact width changes. This happens because the cell gains spatial information largely from the boundaries of cell-cell contact. We study using statistical decision theory the likelihood of a false positive CIL event in the absence of cell-cell contact, and the likelihood of a false negative where CIL does not occur when another cell is present. Our results suggest that the cell is more likely to make incorrect decisions when the contact width is very small or so large that it nears the cell's perimeter. However, in general, we find that cells have the ability to make reasonably reliable CIL decisions even for very narrow (micron-scale) contacts, even if the concentration of interfering ligands is ten times that of the correct ligands.

Although data diffusion embeddings are ubiquitous in unsupervised learning and have proven to be a viable technique for uncovering the underlying intrinsic geometry of data, diffusion embeddings are inherently limited due to their discrete nature. To this end, we propose neural FIM, a method for computing the Fisher information metric (FIM) from point cloud data - allowing for a continuous manifold model for the data. Neural FIM creates an extensible metric space from discrete point cloud data such that information from the metric can inform us of manifold characteristics such as volume and geodesics. We demonstrate Neural FIM's utility in selecting parameters for the PHATE visualization method as well as its ability to obtain information pertaining to local volume illuminating branching points and cluster centers embeddings of a toy dataset and two single-cell datasets of IPSC reprogramming and PBMCs (immune cells).

The structure of topology underpins much of the research on performance and robustness, yet available topology data are typically scarce, necessitating the generation of synthetic graphs with desired properties for testing or release. Prior diffusion-based approaches either embed conditions into the diffusion model, requiring retraining for each attribute and hindering real-time applicability, or use classifier-based guidance post-training, which does not account for topology scale and practical constraints. In this paper, we show from a discrete perspective that gradients from a pre-trained graph-level classifier can be incorporated into the discrete reverse diffusion posterior to steer generation toward specified structural properties. Based on this insight, we propose Classifier-guided Conditional Topology Generation with Persistent Homology (CoPHo), which builds a persistent homology filtration over intermediate graphs and interprets features as guidance signals that steer generation toward the desired properties at each denoising step. Experiments on four generic/network datasets demonstrate that CoPHo outperforms existing methods at matching target metrics, and we further validate its transferability on the QM9 molecular dataset.

Detecting and segmenting object instances is a common task in biomedical applications. Examples range from detecting lesions on functional magnetic resonance images, to the detection of tumours in histopathological images and extracting quantitative single-cell information from microscopy imagery, where cell segmentation is a major bottleneck. Attention-based transformers are state-of-the-art in a range of deep learning fields. They have recently been proposed for segmentation tasks where they are beginning to outperforming other methods. We present a novel attention-based cell detection transformer (Cell-DETR) for direct end-to-end instance segmentation. While the segmentation performance is on par with a state-of-the-art instance segmentation method, Cell-DETR is simpler and faster. We showcase the method's contribution in a the typical use case of segmenting yeast in microstructured environments, commonly employed in systems or synthetic biology. For the specific use case, the proposed method surpasses the state-of-the-art tools for semantic segmentation and additionally predicts the individual object instances. The fast and accurate instance segmentation performance increases the experimental information yield for a posteriori data processing and makes online monitoring of experiments and closed-loop optimal experimental design feasible.

Earlier diagnosis of Leukemia can save thousands of lives annually. The prognosis of leukemia is challenging without the morphological information of White Blood Cells (WBC) and relies on the accessibility of expensive microscopes and the availability of hematologists to analyze Peripheral Blood Samples (PBS). Deep Learning based methods can be employed to assist hematologists. However, these algorithms require a large amount of labeled data, which is not readily available. To overcome this limitation, we have acquired a realistic, generalized, and large dataset. To collect this comprehensive dataset for real-world applications, two microscopes from two different cost spectrums (high-cost HCM and low-cost LCM) are used for dataset capturing at three magnifications (100x, 40x, 10x) through different sensors (high-end camera for HCM, middle-level camera for LCM and mobile-phone camera for both). The high-sensor camera is 47 times more expensive than the middle-level camera and HCM is 17 times more expensive than LCM. In this collection, using HCM at high resolution (100x), experienced hematologists annotated 10.3k WBC types (14) and artifacts, having 55k morphological labels (Cell Size, Nuclear Chromatin, Nuclear Shape, etc.) from 2.4k images of several PBS leukemia patients. Later on, these annotations are transferred to other 2 magnifications of HCM, and 3 magnifications of LCM, and on each camera captured images. Along with the LeukemiaAttri dataset, we provide baselines over multiple object detectors and Unsupervised Domain Adaptation (UDA) strategies, along with morphological information-based attribute prediction. The dataset will be publicly available after publication to facilitate the research in this direction.

The recent surge in performance for image analysis of digitised pathology slides can largely be attributed to the advances in deep learning. Deep models can be used to initially localise various structures in the tissue and hence facilitate the extraction of interpretable features for biomarker discovery. However, these models are typically trained for a single task and therefore scale poorly as we wish to adapt the model for an increasing number of different tasks. Also, supervised deep learning models are very data hungry and therefore rely on large amounts of training data to perform well. In this paper, we present a multi-task learning approach for segmentation and classification of nuclei, glands, lumina and different tissue regions that leverages data from multiple independent data sources. While ensuring that our tasks are aligned by the same tissue type and resolution, we enable meaningful simultaneous prediction with a single network. As a result of feature sharing, we also show that the learned representation can be used to improve the performance of additional tasks via transfer learning, including nuclear classification and signet ring cell detection. As part of this work, we train our developed Cerberus model on a huge amount of data, consisting of over 600K objects for segmentation and 440K patches for classification. We use our approach to process 599 colorectal whole-slide images from TCGA, where we localise 377 million, 900K and 2.1 million nuclei, glands and lumina, respectively and make the results available to the community for downstream analysis.

Cell segmentation is a major bottleneck in extracting quantitative single-cell information from microscopy data. The challenge is exasperated in the setting of microstructured environments. While deep learning approaches have proven useful for general cell segmentation tasks, existing segmentation tools for the yeast-microstructure setting rely on traditional machine learning approaches. Here we present convolutional neural networks trained for multiclass segmenting of individual yeast cells and discerning these from cell-similar microstructures. We give an overview of the datasets recorded for training, validating and testing the networks, as well as a typical use-case. We showcase the method's contribution to segmenting yeast in microstructured environments with a typical synthetic biology application in mind. The models achieve robust segmentation results, outperforming the previous state-of-the-art in both accuracy and speed. The combination of fast and accurate segmentation is not only beneficial for a posteriori data processing, it also makes online monitoring of thousands of trapped cells or closed-loop optimal experimental design feasible from an image processing perspective.

Drug-target interaction (DTI) prediction is crucial for identifying new therapeutics and detecting mechanisms of action. While structure-based methods accurately model physical interactions between a drug and its protein target, cell-based assays such as Cell Painting can better capture complex DTI interactions. This paper introduces MOTIVE, a Morphological cOmpound Target Interaction Graph dataset that comprises Cell Painting features for 11,000 genes and 3,600 compounds along with their relationships extracted from seven publicly available databases. We provide random, cold-source (new drugs), and cold-target (new genes) data splits to enable rigorous evaluation under realistic use cases. Our benchmark results show that graph neural networks that use Cell Painting features consistently outperform those that learn from graph structure alone, feature-based models, and topological heuristics. MOTIVE accelerates both graph ML research and drug discovery by promoting the development of more reliable DTI prediction models. MOTIVE resources are available at https://github.com/carpenter-singh-lab/motive.

Label-free single-cell imaging offers a scalable, non-invasive alternative to fluorescence-based cytometry, yet inferring molecular phenotypes directly from bright-field morphology remains challenging. We present a unified Deep Learning (DL) framework that jointly performs White Blood Cell (WBC) classification and continuous protein-expression regression from label-free Differential Phase Contrast (DPC) images. Our model employs a Hybrid architecture that fuses convolutional fine-grained texture features with transformer-based global representations through a learnable cross-branch gating module, enabling robust morpho-molecular inference from DPC images. To support downstream interpretability, we further incorporate a Large Language Model (LLM) that generates concise, biologically grounded summaries of the predicted cell states. Experiments on the Berkeley Single Cell Computational Microscopy (BSCCM) and Blood Cells Image benchmarks demonstrate strong performance, achieving a 91.3% WBC classification accuracy and a 0.72 Pearson correlation for CD16 expression regression on BSCCM. These results underscore the promise of label-free single-cell imaging for cost-effective hematological profiling, enabling simultaneous phenotype identification and quantitative biomarker estimation without fluorescent staining. The source code is available at https://github.com/saqibnaziir/Single-Cell-Phenotyping.

Precise and scalable instance segmentation of cell nuclei is essential for computational pathology, yet gigapixel Whole-Slide Images pose major computational challenges. Existing approaches rely on patch-based processing and costly post-processing for instance separation, sacrificing context and efficiency. We introduce LSP-DETR (Local Star Polygon DEtection TRansformer), a fully end-to-end framework that uses a lightweight transformer with linear complexity to process substantially larger images without additional computational cost. Nuclei are represented as star-convex polygons, and a novel radial distance loss function allows the segmentation of overlapping nuclei to emerge naturally, without requiring explicit overlap annotations or handcrafted post-processing. Evaluations on PanNuke and MoNuSeg show strong generalization across tissues and state-of-the-art efficiency, with LSP-DETR being over five times faster than the next-fastest leading method. Code and models are available at https://github.com/RationAI/lsp-detr.

Convolutional Neural Networks (CNN) have been successful in processing data signals that are uniformly sampled in the spatial domain (e.g., images). However, most data signals do not natively exist on a grid, and in the process of being sampled onto a uniform physical grid suffer significant aliasing error and information loss. Moreover, signals can exist in different topological structures as, for example, points, lines, surfaces and volumes. It has been challenging to analyze signals with mixed topologies (for example, point cloud with surface mesh). To this end, we develop mathematical formulations for Non-Uniform Fourier Transforms (NUFT) to directly, and optimally, sample nonuniform data signals of different topologies defined on a simplex mesh into the spectral domain with no spatial sampling error. The spectral transform is performed in the Euclidean space, which removes the translation ambiguity from works on the graph spectrum. Our representation has four distinct advantages: (1) the process causes no spatial sampling error during the initial sampling, (2) the generality of this approach provides a unified framework for using CNNs to analyze signals of mixed topologies, (3) it allows us to leverage state-of-the-art backbone CNN architectures for effective learning without having to design a particular architecture for a particular data structure in an ad-hoc fashion, and (4) the representation allows weighted meshes where each element has a different weight (i.e., texture) indicating local properties. We achieve results on par with the state-of-the-art for the 3D shape retrieval task, and a new state-of-the-art for the point cloud to surface reconstruction task.

Next generations of radio surveys are expected to identify tens of millions of new sources, and identifying and classifying their morphologies will require novel and more efficient methods. Self-Organising Maps (SOMs), a type of unsupervised machine learning, can be used to address this problem. We map 251,259 multi-Gaussian sources from Rapid ASKAP Continuum Survey (RACS) onto a SOM with discrete neurons. Similarity metrics, such as Euclidean distances, can be used to identify the best-matching neuron or unit (BMU) for each input image. We establish a reliability threshold by visually inspecting a subset of input images and their corresponding BMU. We label the individual neurons based on observed morphologies and these labels are included in our value-added catalogue of RACS sources. Sources for which the Euclidean distance to their BMU is lesssim 5 (accounting for approximately 79% of sources) have an estimated >90% reliability for their SOM-derived morphological labels. This reliability falls to less than 70% at Euclidean distances gtrsim 7. Beyond this threshold it is unlikely that the morphological label will accurately describe a given source. Our catalogue of complex radio sources from RACS with their SOM-derived morphological labels from this work will be made publicly available.

Medical image classification requires not only high predictive performance but also interpretability to ensure clinical trust and adoption. Graph Neural Networks (GNNs) offer a powerful framework for modeling relational structures within datasets; however, standard GNNs often operate as black boxes, limiting transparency and usability, particularly in clinical settings. In this work, we present an interpretable graph-based learning framework named FireGNN that integrates trainable fuzzy rules into GNNs for medical image classification. These rules embed topological descriptors - node degree, clustering coefficient, and label agreement - using learnable thresholds and sharpness parameters to enable intrinsic symbolic reasoning. Additionally, we explore auxiliary self-supervised tasks (e.g., homophily prediction, similarity entropy) as a benchmark to evaluate the contribution of topological learning. Our fuzzy-rule-enhanced model achieves strong performance across five MedMNIST benchmarks and the synthetic dataset MorphoMNIST, while also generating interpretable rule-based explanations. To our knowledge, this is the first integration of trainable fuzzy rules within a GNN. Source Code: https://github.com/basiralab/FireGNN

The inference of topological principles is a key problem in structured reconstruction. We observe that wrongly predicted topological relationships are often incurred by the lack of holistic geometry clues in low-level features. Inspired by the fact that massive signals can be compactly described with frequency analysis, we experimentally explore the efficiency and tendency of learning structure geometry in the frequency domain. Accordingly, we propose a frequency-domain feature learning strategy (F-Learn) to fuse scattered geometric fragments holistically for topology-intact structure reasoning. Benefiting from the parsimonious design, the F-Learn strategy can be easily deployed into a deep reconstructor with a lightweight model modification. Experiments demonstrate that the F-Learn strategy can effectively introduce structure awareness into geometric primitive detection and topology inference, bringing significant performance improvement to final structured reconstruction. Code and pre-trained models are available at https://github.com/Geo-Tell/F-Learn.

Real-world phenomena do not generate arbitrary variability: their signals concentrate on compact, low-variability subsets of functional space, enabling rapid generalization from few examples. A small child can recognize a dog after extremely limited exposure because the perceptual manifold of "dog" is compact, structured, and low-dimensional. We formalize this principle through a deterministic functional-topological framework in which the set of valid realizations produced by a physical process forms a compact subset of a Banach space, endowed with stable invariants, a finite Hausdorff radius, and an induced continuous perceptual functional. This geometry provides explicit limits on knowledge, conditions for identifiability, and guarantees for generalization from sparse evidence -- properties fundamental to both natural and artificial intelligence. Across electromechanical, electrochemical, and physiological domains, we show that real-world processes consistently generate compact perceptual manifolds with the same geometric characteristics. Their boundaries can be discovered in a fully self-supervised manner as the empirical radius saturates with increasing sampling, even when the governing equations are unknown. These results demonstrate that deterministic functional topology offers a unified mathematical foundation for perception, representation, and world-model construction. It provides a geometric explanation for why biological learners and self-supervised AI systems can generalize from few observations, and establishes compact perceptual manifolds as a fundamental building block for future AI architectures. Finally, this work unifies biological perception and modern self-supervised models under a single geometric principle: both derive their generalization ability from the compactness and invariants of real-world perceptual manifolds.

Driven by advancements in deep learning, computer-aided diagnoses have made remarkable progress. However, outside controlled laboratory settings, algorithms may encounter several challenges. In the medical domain, these difficulties often stem from limited data availability due to ethical and legal restrictions, as well as the high cost and time required for expert annotations-especially in the face of emerging or rare diseases. In this context, open-set recognition plays a vital role by identifying whether a sample belongs to one of the known classes seen during training or should be rejected as an unknown. Recent studies have shown that features learned in the later stages of deep neural networks are observed to cluster around their class means, which themselves are arranged as individual vertices of a regular simplex [32]. The proposed method introduces a loss function designed to reject samples of unknown classes effectively by penalizing open space regions using auxiliary datasets. This approach achieves significant performance gain across four MedMNIST datasets-BloodMNIST, OCTMNIST, DermaMNIST, TissueMNIST and a publicly available skin dataset [29] outperforming state-of-the-art techniques.

Computational pathology has made significant progress in recent years, fueling advances in both fundamental disease understanding and clinically ready tools. This evolution is driven by the availability of large amounts of digitized slides and specialized deep learning methods and models. Multiple self-supervised foundation feature extractors have been developed, enabling downstream predictive applications from cell segmentation to tumor sub-typing and survival analysis. In contrast, generative foundation models designed specifically for histopathology remain scarce. Such models could address tasks that are beyond the capabilities of feature extractors, such as virtual staining. In this paper, we introduce CytoSyn, a state-of-the-art foundation latent diffusion model that enables the guided generation of highly realistic and diverse histopathology H&E-stained images, as shown in an extensive benchmark. We explored methodological improvements, training set scaling, sampling strategies and slide-level overfitting, culminating in the improved CytoSyn-v2, and compared our work to PixCell, a state-of-the-art model, in an in-depth manner. This comparison highlighted the strong sensitivity of both diffusion models and performance metrics to preprocessing-specific details such as JPEG compression. Our model has been trained on a dataset obtained from more than 10,000 TCGA diagnostic whole-slide images of 32 different cancer types. Despite being trained only on oncology slides, it maintains state-of-the-art performance generating inflammatory bowel disease images. To support the research community, we publicly release CytoSyn's weights, its training and validation datasets, and a sample of synthetic images in this repository: https://huggingface.co/Owkin-Bioptimus/CytoSyn.

Recent advances in microscopy have enabled the rapid generation of terabytes of image data in cell biology and biomedical research. Vision-language models (VLMs) offer a promising solution for large-scale biological image analysis, enhancing researchers' efficiency, identifying new image biomarkers, and accelerating hypothesis generation and scientific discovery. However, there is a lack of standardized, diverse, and large-scale vision-language benchmarks to evaluate VLMs' perception and cognition capabilities in biological image understanding. To address this gap, we introduce {\mu}-Bench, an expert-curated benchmark encompassing 22 biomedical tasks across various scientific disciplines (biology, pathology), microscopy modalities (electron, fluorescence, light), scales (subcellular, cellular, tissue), and organisms in both normal and abnormal states. We evaluate state-of-the-art biomedical, pathology, and general VLMs on {\mu}-Bench and find that: i) current models struggle on all categories, even for basic tasks such as distinguishing microscopy modalities; ii) current specialist models fine-tuned on biomedical data often perform worse than generalist models; iii) fine-tuning in specific microscopy domains can cause catastrophic forgetting, eroding prior biomedical knowledge encoded in their base model. iv) weight interpolation between fine-tuned and pre-trained models offers one solution to forgetting and improves general performance across biomedical tasks. We release {\mu}-Bench under a permissive license to accelerate the research and development of microscopy foundation models.

Vision-language models (VLMs) achieve strong multimodal performance, yet how computation is organized across populations of neurons remains poorly understood. In this work, we study VLMs through the lens of neural topology, representing each layer as a within-layer correlation graph derived from neuron-neuron co-activations. This view allows us to ask whether population-level structure is behaviorally meaningful, how it changes across modalities and depth, and whether it identifies causally influential internal components under intervention. We show that correlation topology carries recoverable behavioral signal; moreover, cross-modal structure progressively consolidates with depth around a compact set of recurrent hub neurons, whose targeted perturbation substantially alters model output. Neural topology thus emerges as a meaningful intermediate scale for VLM interpretability: richer than local attribution, more tractable than full circuit recovery, and empirically tied to multimodal behavior. Code is publicly available at https://github.com/he-h/vlm-graph-probing.

Masked image modelling (MIM) is a powerful self-supervised representation learning paradigm, whose potential has not been widely demonstrated in medical image analysis. In this work, we show the capacity of MIM to capture rich semantic representations of Haemotoxylin & Eosin (H&E)-stained images at the nuclear level. Inspired by Bidirectional Encoder representation from Image Transformers (BEiT), we split the images into smaller patches and generate corresponding discrete visual tokens. In addition to the regular grid-based patches, typically used in visual Transformers, we introduce patches of individual cell nuclei. We propose positional encoding of the irregular distribution of these structures within an image. We pre-train the model in a self-supervised manner on H&E-stained whole-slide images of diffuse large B-cell lymphoma, where cell nuclei have been segmented. The pre-training objective is to recover the original discrete visual tokens of the masked image on the one hand, and to reconstruct the visual tokens of the masked object instances on the other. Coupling these two pre-training tasks allows us to build powerful, context-aware representations of nuclei. Our model generalizes well and can be fine-tuned on downstream classification tasks, achieving improved cell classification accuracy on PanNuke dataset by more than 5% compared to current instance segmentation methods.

High-throughput screening techniques, such as microscopy imaging of cellular responses to genetic and chemical perturbations, play a crucial role in drug discovery and biomedical research. However, robust perturbation screening for de novo cell lines remains challenging due to the significant morphological and biological heterogeneity across cell lines. To address this, we propose a novel framework that integrates external biological knowledge into existing pretraining strategies to enhance microscopy image profiling models. Our approach explicitly disentangles perturbation-specific and cell line-specific representations using external biological information. Specifically, we construct a knowledge graph leveraging protein interaction data from STRING and Hetionet databases to guide models toward perturbation-specific features during pretraining. Additionally, we incorporate transcriptomic features from single-cell foundation models to capture cell line-specific representations. By learning these disentangled features, our method improves the generalization of imaging models to de novo cell lines. We evaluate our framework on the RxRx database through one-shot fine-tuning on an RxRx1 cell line and few-shot fine-tuning on cell lines from the RxRx19a dataset. Experimental results demonstrate that our method enhances microscopy image profiling for de novo cell lines, highlighting its effectiveness in real-world phenotype-based drug discovery applications.

The enduring legacy of Euclidean geometry underpins classical machine learning, which, for decades, has been primarily developed for data lying in Euclidean space. Yet, modern machine learning increasingly encounters richly structured data that is inherently nonEuclidean. This data can exhibit intricate geometric, topological and algebraic structure: from the geometry of the curvature of space-time, to topologically complex interactions between neurons in the brain, to the algebraic transformations describing symmetries of physical systems. Extracting knowledge from such non-Euclidean data necessitates a broader mathematical perspective. Echoing the 19th-century revolutions that gave rise to non-Euclidean geometry, an emerging line of research is redefining modern machine learning with non-Euclidean structures. Its goal: generalizing classical methods to unconventional data types with geometry, topology, and algebra. In this review, we provide an accessible gateway to this fast-growing field and propose a graphical taxonomy that integrates recent advances into an intuitive unified framework. We subsequently extract insights into current challenges and highlight exciting opportunities for future development in this field.

We introduce CurveBench, a benchmark for hierarchical topological reasoning from visual input. CurveBench consists of 756 images of pairwise non-intersecting Jordan curves across easy, polygonal, topographic-inspired, maze-like, and dense counting configurations. Each image is annotated with a rooted tree encoding the containment relations between planar regions. We formulate the task as structured prediction: given an image, a model must recover the full rooted containment tree induced by the curves. Despite the visual simplicity of the task, the strongest evaluated model, Gemini 3.1 Pro, achieves only 71.1\% tree-generation accuracy on CurveBench-Easy and 19.1\% on CurveBench-Hard. We further demonstrate benchmark utility through RLVR-style fine-tuning of open-weight vision-language models. Our trained Qwen3-VL-8B model improves over Qwen-3-VL-8B-Thinking from 2.8\% to 33.3\% tree-generation accuracy on CurveBench-Easy, exceeding GPT-5.4 and Claude Opus 4.5 under our evaluation protocol. The remaining gap, especially on CurveBench-Hard, shows that exact topology-aware visual reasoning remains far from solved.

Single-cell technologies generate high-dimensional point clouds of cells, enabling detailed characterization of complex patient states and treatment responses. Yet each patient is represented by an irregular point cloud rather than a simple vector, making it difficult to directly quantify and compare biological differences between individuals. Nonlinear methods such as kernels and neural networks achieve predictive accuracy but act as black boxes, offering little biological interpretability. To address these limitations, we adapt the Linear Optimal Transport (LOT) framework to this setting, embedding irregular point clouds into a fixed-dimensional Euclidean space while preserving distributional structure. This embedding provides a principled linear representation that preserves optimal transport geometry while enabling downstream analysis. It also forms a registration between any two patients, enabling direct comparison of their cellular distributions. Within this space, LOT enables: (i) accurate and interpretable classification of COVID-19 patient states, where classifier weights map back to specific markers and spatial regions driving predictions; and (ii) synthetic data generation for patient-derived organoids, exploiting the linearity of the LOT embedding. LOT barycenters yield averaged cellular profiles representing combined conditions or samples, supporting drug interaction testing. Together, these results establish LOT as a unified framework that bridges predictive performance, interpretability, and generative modeling. By transforming heterogeneous point clouds into structured embeddings directly traceable to the original data, LOT opens new opportunities for understanding immune variation and treatment effects in high-dimensional biological systems.

Fully automatic cardiac segmentation can be a fast and reproducible method to extract clinical measurements from an echocardiography examination. The U-Net architecture is the current state-of-the-art deep learning architecture for medical segmentation and can segment cardiac structures in real-time with average errors comparable to inter-observer variability. However, this architecture still generates large outliers that are often anatomically incorrect. This work uses the concept of graph convolutional neural networks that predict the contour points of the structures of interest instead of labeling each pixel. We propose a graph architecture that uses two convolutional rings based on cardiac anatomy and show that this eliminates anatomical incorrect multi-structure segmentations on the publicly available CAMUS dataset. Additionally, this work contributes with an ablation study on the graph convolutional architecture and an evaluation of clinical measurements on the clinical HUNT4 dataset. Finally, we propose to use the inter-model agreement of the U-Net and the graph network as a predictor of both the input and segmentation quality. We show this predictor can detect out-of-distribution and unsuitable input images in real-time. Source code is available online: https://github.com/gillesvntnu/GCN_multistructure

Topology reasoning aims to comprehensively understand road scenes and present drivable routes in autonomous driving. It requires detecting road centerlines (lane) and traffic elements, further reasoning their topology relationship, i.e., lane-lane topology, and lane-traffic topology. In this work, we first present that the topology score relies heavily on detection performance on lane and traffic elements. Therefore, we introduce a powerful 3D lane detector and an improved 2D traffic element detector to extend the upper limit of topology performance. Further, we propose TopoMLP, a simple yet high-performance pipeline for driving topology reasoning. Based on the impressive detection performance, we develop two simple MLP-based heads for topology generation. TopoMLP achieves state-of-the-art performance on OpenLane-V2 benchmark, i.e., 41.2% OLS with ResNet-50 backbone. It is also the 1st solution for 1st OpenLane Topology in Autonomous Driving Challenge. We hope such simple and strong pipeline can provide some new insights to the community. Code is at https://github.com/wudongming97/TopoMLP.

Immunohistochemical (IHC) staining highlights the molecular information critical to diagnostics in tissue samples. However, compared to H&E staining, IHC staining can be much more expensive in terms of both labor and the laboratory equipment required. This motivates recent research that demonstrates that the correlations between the morphological information present in the H&E-stained slides and the molecular information in the IHC-stained slides can be used for H&E-to-IHC stain translation. However, due to a lack of pixel-perfect H&E-IHC groundtruth pairs, most existing methods have resorted to relying on expert annotations. To remedy this situation, we present a new loss function, Adaptive Supervised PatchNCE (ASP), to directly deal with the input to target inconsistencies in a proposed H&E-to-IHC image-to-image translation framework. The ASP loss is built upon a patch-based contrastive learning criterion, named Supervised PatchNCE (SP), and augments it further with weight scheduling to mitigate the negative impact of noisy supervision. Lastly, we introduce the Multi-IHC Stain Translation (MIST) dataset, which contains aligned H&E-IHC patches for 4 different IHC stains critical to breast cancer diagnosis. In our experiment, we demonstrate that our proposed method outperforms existing image-to-image translation methods for stain translation to multiple IHC stains. All of our code and datasets are available at https://github.com/lifangda01/AdaptiveSupervisedPatchNCE.

Protein representation learning (PRL) is crucial for understanding structure-function relationships, yet current sequence- and graph-based methods fail to capture the hierarchical organization inherent in protein structures. We introduce Topotein, a comprehensive framework that applies topological deep learning to PRL through the novel Protein Combinatorial Complex (PCC) and Topology-Complete Perceptron Network (TCPNet). Our PCC represents proteins at multiple hierarchical levels -- from residues to secondary structures to complete proteins -- while preserving geometric information at each level. TCPNet employs SE(3)-equivariant message passing across these hierarchical structures, enabling more effective capture of multi-scale structural patterns. Through extensive experiments on four PRL tasks, TCPNet consistently outperforms state-of-the-art geometric graph neural networks. Our approach demonstrates particular strength in tasks such as fold classification which require understanding of secondary structure arrangements, validating the importance of hierarchical topological features for protein analysis.