Transitive Representation Learning Enhances Histopathology Annotation

The characterization of histopathology with AI promises to assist clinical decision-making, but it is currently limited due to coarse-grained annotations that miss cellular identities. To overcome this gap, we bridge histopathological images, gene expression profiles, and natural-language descriptions using SpatialWhisperer , a trimodal contrastive learning model. Our training integrates community-scale datasets comprising spatially resolved gene expression profiles paired with histopathology images, as well as single-cell gene expression profiles with detailed annotations. The shared gene expression modality implies a transitive relationship between images and textual annotations, which our method leverages to enable accurate zero-shot cell type annotation directly from H&E images. SpatialWhisperer outperforms published baselines, achieving relative AUROC gains of up to 15.9% across three benchmarks spanning 19 tissues and 20 cell types. When training with data from all three modality pairs, we observe performance gains in low-data regimes. We formalize our approach and present a sufficient condition under which this transitive alignment is induced. Our work establishes transitive representation learning for fine-grained interpretation of histopathology images.