Understanding Cell Fate Decisions with Temporal Attention

Understanding non-genetic determinants of cell fate is critical for developing and improving cancer therapies, as genetically identical cells can exhibit divergent outcomes under the same treatment conditions. In this work, we present a deep learning approach for cell fate prediction from raw long-term live-cell recordings of cancer cell populations under chemotherapeutic treatment. Our Transformer model is trained to predict cell fate directly from raw image sequences, without relying on predefined morphological or molecular features. Beyond classification, we introduce a comprehensive explainability framework for interpreting the temporal and morphological cues guiding the model's predictions. We demonstrate that prediction of cell outcomes is possible based on the video only, our model achieves balanced accuracy of 0.94 and an F1-score of 0.93. Attention and masking experiments further indicate that the signal predictive of the cell fate is not uniquely located in the final frames of a cell trajectory, as reliable predictions are possible up to 10 h before the event. Our analysis reveals distinct temporal distribution of predictive information in the mitotic and apoptotic sequences, as well as the role of cell morphology and p53 signaling in determining cell outcomes. Together, these findings demonstrate that attention-based temporal models enable accurate cell fate prediction while providing biologically interpretable insights into non-genetic determinants of cellular decision-making. The code is available at https://github.com/bozeklab/Cell-Fate-Prediction.

Self-Supervised ImageNet Representations for In Vivo Confocal Microscopy: Tortuosity Grading without Segmentation Maps

The tortuosity of corneal nerve fibers are used as indication for different diseases. Current state-of-the-art methods for grading the tortuosity heavily rely on expensive segmentation maps of these nerve fibers. In this paper, we demonstrate that self-supervised pretrained features from ImageNet are transferable to the domain of in vivo confocal microscopy. We show that DINO should not be disregarded as a deep learning model for medical imaging, although it was superseded by two later versions. After careful fine-tuning, DINO improves upon the state-of-the-art in terms of accuracy (84,25%) and sensitivity (77,97%). Our fine-tuned model focuses on the key morphological elements in grading without the use of segmentation maps.

Context-aware Skin Cancer Epithelial Cell Classification with Scalable Graph Transformers

Whole-slide images (WSIs) from cancer patients contain rich information that can be used for medical diagnosis or to follow treatment progress. To automate their analysis, numerous deep learning methods based on convolutional neural networks and Vision Transformers have been developed and have achieved strong performance in segmentation and classification tasks. However, due to the large size and complex cellular organization of WSIs, these models rely on patch-based representations, losing vital tissue-level context. We propose using scalable Graph Transformers on a full-WSI cell graph for classification. We evaluate this methodology on a challenging task: the classification of healthy versus tumor epithelial cells in cutaneous squamous cell carcinoma (cSCC), where both cell types exhibit very similar morphologies and are therefore difficult to differentiate for image-based approaches. We first compared image-based and graph-based methods on a single WSI. Graph Transformer models SGFormer and DIFFormer achieved balanced accuracies of $85.2 \pm 1.5$ ($\pm$ standard error) and $85.1 \pm 2.5$ in 3-fold cross-validation, respectively, whereas the best image-based method reached $81.2 \pm 3.0$. By evaluating several node feature configurations, we found that the most informative representation combined morphological and texture features as well as the cell classes of non-epithelial cells, highlighting the importance of the surrounding cellular context. We then extended our work to train on several WSIs from several patients. To address the computational constraints of image-based models, we extracted four $2560 \times 2560$ pixel patches from each image and converted them into graphs. In this setting, DIFFormer achieved a balanced accuracy of $83.6 \pm 1.9$ (3-fold cross-validation), while the state-of-the-art image-based model CellViT256 reached $78.1 \pm 0.5$.

AMAP-APP: Efficient Segmentation and Morphometry Quantification of Fluorescent Microscopy Images of Podocytes

Background: Automated podocyte foot process quantification is vital for kidney research, but the established "Automatic Morphological Analysis of Podocytes" (AMAP) method is hindered by high computational demands, a lack of a user interface, and Linux dependency. We developed AMAP-APP, a cross-platform desktop application designed to overcome these barriers. Methods: AMAP-APP optimizes efficiency by replacing intensive instance segmentation with classic image processing while retaining the original semantic segmentation model. It introduces a refined Region of Interest (ROI) algorithm to improve precision. Validation involved 365 mouse and human images (STED and confocal), benchmarking performance against the original AMAP via Pearson correlation and Two One-Sided T-tests (TOST). Results: AMAP-APP achieved a 147-fold increase in processing speed on consumer hardware. Morphometric outputs (area, perimeter, circularity, and slit diaphragm density) showed high correlation (r>0.90) and statistical equivalence (TOST P<0.05) to the original method. Additionally, the new ROI algorithm demonstrated superior accuracy compared to the original, showing reduced deviation from manual delineations. Conclusion: AMAP-APP democratizes deep learning-based podocyte morphometry. By eliminating the need for high-performance computing clusters and providing a user-friendly interface for Windows, macOS, and Linux, it enables widespread adoption in nephrology research and potential clinical diagnostics.

ActiTect: A Generalizable Machine Learning Pipeline for REM Sleep Behavior Disorder Screening through Standardized Actigraphy

Isolated rapid eye movement sleep behavior disorder (iRBD) is a major prodromal marker of $α$-synucleinopathies, often preceding the clinical onset of Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. While wrist-worn actimeters hold significant potential for detecting RBD in large-scale screening efforts by capturing abnormal nocturnal movements, they become inoperable without a reliable and efficient analysis pipeline. This study presents ActiTect, a fully automated, open-source machine learning tool to identify RBD from actigraphy recordings. To ensure generalizability across heterogeneous acquisition settings, our pipeline includes robust preprocessing and automated sleep-wake detection to harmonize multi-device data and extract physiologically interpretable motion features characterizing activity patterns. Model development was conducted on a cohort of 78 individuals, yielding strong discrimination under nested cross-validation (AUROC = 0.95). Generalization was confirmed on a blinded local test set (n = 31, AUROC = 0.86) and on two independent external cohorts (n = 113, AUROC = 0.84; n = 57, AUROC = 0.94). To assess real-world robustness, leave-one-dataset-out cross-validation across the internal and external cohorts demonstrated consistent performance (AUROC range = 0.84-0.89). A complementary stability analysis showed that key predictive features remained reproducible across datasets, supporting the final pooled multi-center model as a robust pre-trained resource for broader deployment. By being open-source and easy to use, our tool promotes widespread adoption and facilitates independent validation and collaborative improvements, thereby advancing the field toward a unified and generalizable RBD detection model using wearable devices.