Multimodal Outer Arithmetic Block Dual Fusion of Whole Slide Images and Omics Data for Precision Oncology

The integration of DNA methylation data with a Whole Slide Image (WSI) offers significant potential for enhancing the diagnostic precision of central nervous system (CNS) tumor classification in neuropathology. While existing approaches typically integrate encoded omic data with histology at either an early or late fusion stage, the potential of reintroducing omic data through dual fusion remains unexplored. In this paper, we propose the use of omic embeddings during early and late fusion to capture complementary information from local (patch-level) to global (slide-level) interactions, boosting performance through multimodal integration. In the early fusion stage, omic embeddings are projected onto WSI patches in latent-space, which generates embeddings that encapsulate per-patch molecular and morphological insights. This effectively incorporates omic information into the spatial representation of the WSI. These embeddings are then refined with a Multiple Instance Learning gated attention mechanism which attends to diagnostic patches. In the late fusion stage, we reintroduce the omic data by fusing it with slide-level omic-WSI embeddings using a Multimodal Outer Arithmetic Block (MOAB), which richly intermingles features from both modalities, capturing their correlations and complementarity. We demonstrate accurate CNS tumor subtyping across 20 fine-grained subtypes and validate our approach on benchmark datasets, achieving improved survival prediction on TCGA-BLCA and competitive performance on TCGA-BRCA compared to state-of-the-art methods. This dual fusion strategy enhances interpretability and classification performance, highlighting its potential for clinical diagnostics.