biostudies-literatureUnknownLiu SNIDA NIH HHSNHGRI NIH HHSNCI NIH HHSNIH HHSThe intricate spatial organization and molecular communication among cells are fundamental to multicellular systems. Spatial transcriptomics (ST) enables gene expression profiling while preserving spatial context, providing rich data for studying cellular interactions and tissue dynamics. However, most existing computational approaches focus on embedding-based tasks and provide limited generative capacity for simulating cell behavior <i>in situ</i>. Moreover, accurately interpreting spatial interactions requires extensive biological knowledge, which current models do not incorporate. Here, we introduce TissueNarrator, a framework that reformulates spatial omics analysis as a language modeling problem. By representing tissue sections as spatial sentences - rank-based gene lists augmented wibioRxiv : the preprint server for biology2025.11.24.690325https://www.ebi.ac.uk/biostudies/studies/S-EPMC12697357biostudies-literatureTissueNarrator: Generative Modeling of Spatial Transcriptomics with Large Language Models.PMC12697357R21 DA061481R03 OD039980UM1 HG011593R01 HG012303UH3 CA268202R01 HG007352Liang STang JMa JLiu SfalseTissueNarrator: Generative Modeling of Spatial Transcriptomics with Large Language Models.The intricate spatial organization and molecular communication among cells are fundamental to multicellular systems. Spatial transcriptomics (ST) enables gene expression profiling while preserving spatial context, providing rich data for studying cellular interactions and tissue dynamics. However, most existing computational approaches focus on embedding-based tasks and provide limited generative capacity for simulating cell behavior <i>in situ</i>. Moreover, accurately interpreting spatial interactions requires extensive biological knowledge, which current models do not incorporate. Here, we introduce TissueNarrator, a framework that reformulates spatial omics analysis as a language modeling problem. By representing tissue sections as spatial sentences - rank-based gene lists augmented wi2025-01-01T00:00:00Z2025 Nov2026-06-14T03:15:17.928Z2026-06-14T03:08:49.393ZS-EPMC126973574139462810.1101/2025.11.24.690325