Unravelling tumour spatiotemporal heterogeneity using spatial multimodal data

Analysing the genome, epigenome, transcriptome, proteome, and metabolome within the spatial context of cells has transformed our understanding of tumour spatiotemporal heterogeneity. Advances in spatial multi-omics technologies now reveal complex molecular interactions shaping cellular behaviour and tissue dynamics. This review highlights key technologies and computational methods that have advanced spatial domain identification and their pseudo-relations, as well as inference of intra- and inter-cellular molecular networks that drive disease progression. We also discuss strategies to address major challenges, including data sparsity, high-dimensionality, scalability, and heterogeneity. Furthermore, we outline how spatial multi-omics enables novel insights into disease mechanisms, advancing precision medicine and informing targeted therapies. KEY POINTS: Advancements in spatial multi-omics facilitate our understanding of tumour spatiotemporal heterogeneity. AI-driven multimodal models uncover complex molecular interactions that underlie cellular behaviours and tissue dynamics. Combining multi-omics technologies and AI-enabled bioinformatics tools helps predict critical disease stages, such as pre-cancer, advancing precision medicine, and informing targeted therapeutic strategies.