Maximilian Diehn

Sakib Mostafa, Tarik Massoud, Maximilian Diehn et al.

Tabular data are central to biomedical research, from liquid biopsy and bulk and single-cell transcriptomics to electronic health records and phenotypic profiling. Unlike images or sequences, however, tabular datasets lack intrinsic spatial organization: features are treated as unordered dimensions, and their relationships must be inferred implicitly by the model. This limits the ability of vision architectures to exploit local structure and higher-order feature interactions in non-spatial biomedical data. Here we introduce Dynamic Feature Mapping (Dynomap), an end-to-end deep learning framework that learns a task-optimized spatial topology of features directly from data. Dynomap jointly optimizes feature placement and prediction through a fully differentiable rendering mechanism, without relying on heuristics, predefined groupings, or external priors. By transforming high-dimensional tabular vectors into learned feature maps, Dynomap enables vision-based models to operate effectively on unordered biomedical inputs. Across multiple clinical and biological datasets, Dynomap consistently outperformed classical machine learning, modern deep tabular models, and existing vector-to-image approaches. In liquid biopsy data, Dynomap organized clinically relevant gene signatures into coherent spatial patterns and improved multiclass cancer subtype prediction accuracy by up to 18%. In a Parkinson disease voice dataset, it clustered disease-associated acoustic descriptors and improved accuracy by up to 8%. Similar gains and interpretable feature organization were observed in additional biomedical datasets. These results establish Dynomap as a general strategy for bridging tabular and vision-based deep learning and for uncovering structured, clinically relevant patterns in high-dimensional biomedical data.

Yuwei Xue, Sakib Mostafa, James Zou et al.

Biological systems are governed by structured molecular interactions, where pathways, regulatory circuits, and functional gene relationships shape cellular behavior and disease progression. Much of this knowledge is naturally represented as graphs. However, most biomedical AI models cannot directly use graph-encoded biological knowledge and instead require compressed low-dimensional representations, which can lose important structure and reduce performance, especially in limited-sample clinical studies. Here, we introduce Graph-in-Graph (GiG), a knowledge graph-modulated deep learning framework for data-efficient clinical prediction. GiG represents each patient as a standalone modular graph, in which curated biological knowledge graphs define edges and patient-specific measurements, such as gene expression, define node features. This design allows multiple biological knowledge graphs to be integrated while preserving gene-gene interactions and pathway topology during patient-level representation learning. Across cohorts comprising nearly 9,700 patients and five clinical tasks, including liquid biopsy cancer detection, prostate cancer diagnosis, and 32-class pan-cancer classification, GiG consistently outperforms traditional and state-of-the-art methods, with the largest gains in limited-sample settings. On the challenging prostate cancer diagnosis task, GiG improves macro-F1 by up to 49 percentage points relative to competing methods. Control experiments replacing real pathway graphs with random topologies confirm that these gains arise from biologically grounded knowledge graph structure rather than graph modeling alone. These findings show that knowledge graph-modulated deep learning can improve robustness, interpretability, and sample efficiency in clinical data analysis, and provide a principled framework for integrating biological knowledge graphs into predictive modeling.

Jinxi Xiang, Siyu Hou, Yuchen Li et al.

Spatial transcriptomics (ST) enables gene expression mapping within anatomical context but remains costly and low-throughput. Hematoxylin and eosin (H\&E) staining offers rich morphology yet lacks molecular resolution. We present \textbf{\ours} (\textbf{S}patial \textbf{T}ranscriptomics and hist\textbf{O}logy \textbf{R}epresentation \textbf{M}odel), a foundation model trained on 1.2 million spatially resolved transcriptomic profiles with matched histology across 18 organs. Using a hierarchical architecture integrating morphological features, gene expression, and spatial context, STORM bridges imaging and omics through robust molecular--morphological representations. STORM enhances spatial domain discovery, producing biologically coherent tissue maps, and outperforms existing methods in predicting spatial gene expression from H\&E images across 11 tumor types. The model is platform-agnostic, performing consistently across Visium, Xenium, Visium HD, and CosMx. Applied to 23 independent cohorts comprising 7,245 patients, STORM significantly improves immunotherapy response prediction and prognostication over established biomarkers, providing a scalable framework for spatially informed discovery and clinical precision medicine.

Xiangde Luo, Xiyue Wang, Feyisope Eweje et al.

Histopathology is essential for disease diagnosis and treatment decision-making. Recent advances in artificial intelligence (AI) have enabled the development of pathology foundation models that learn rich visual representations from large-scale whole-slide images (WSIs). However, existing models are often trained on disparate datasets using varying strategies, leading to inconsistent performance and limited generalizability. Here, we introduce ELF (Ensemble Learning of Foundation models), a novel framework that integrates five state-of-the-art pathology foundation models to generate unified slide-level representations. Trained on 53,699 WSIs spanning 20 anatomical sites, ELF leverages ensemble learning to capture complementary information from diverse models while maintaining high data efficiency. Unlike traditional tile-level models, ELF's slide-level architecture is particularly advantageous in clinical contexts where data are limited, such as therapeutic response prediction. We evaluated ELF across a wide range of clinical applications, including disease classification, biomarker detection, and response prediction to major anticancer therapies, cytotoxic chemotherapy, targeted therapy, and immunotherapy, across multiple cancer types. ELF consistently outperformed all constituent foundation models and existing slide-level models, demonstrating superior accuracy and robustness. Our results highlight the power of ensemble learning for pathology foundation models and suggest ELF as a scalable and generalizable solution for advancing AI-assisted precision oncology.

Stephen Baek, Yusen He, Bryan G. Allen et al.

Non-small-cell lung cancer (NSCLC) represents approximately 80-85% of lung cancer diagnoses and is the leading cause of cancer-related death worldwide. Recent studies indicate that image-based radiomics features from positron emission tomography-computed tomography (PET/CT) images have predictive power on NSCLC outcomes. To this end, easily calculated functional features such as the maximum and the mean of standard uptake value (SUV) and total lesion glycolysis (TLG) are most commonly used for NSCLC prognostication, but their prognostic value remains controversial. Meanwhile, convolutional neural networks (CNN) are rapidly emerging as a new premise for cancer image analysis, with significantly enhanced predictive power compared to other hand-crafted radiomics features. Here we show that CNN trained to perform the tumor segmentation task, with no other information than physician contours, identify a rich set of survival-related image features with remarkable prognostic value. In a retrospective study on 96 NSCLC patients before stereotactic-body radiotherapy (SBRT), we found that the CNN segmentation algorithm (U-Net) trained for tumor segmentation in PET/CT images, contained features having strong correlation with 2- and 5-year overall and disease-specific survivals. The U-net algorithm has not seen any other clinical information (e.g. survival, age, smoking history) than the images and the corresponding tumor contours provided by physicians. Furthermore, through visualization of the U-Net, we also found convincing evidence that the regions of progression appear to match with the regions where the U-Net features identified patterns that predicted higher likelihood of death. We anticipate our findings will be a starting point for more sophisticated non-intrusive patient specific cancer prognosis determination.