Maximilian Diehn
Publications
A Multimodal Foundation Model of Spatial Transcriptomics and Histology for Biological Discovery and Clinical Prediction
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.
Vision-based Deep Learning Analysis of Unordered Biomedical Tabular Datasets via Optimal Spatial Cartography
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.