Annotating Spatial Multi-Omics Spot-Level Niche Types Using Bi-View Retrieval-Augmented Generation With SpotTypeLLM

Spatial multi-omics techniques generate extensive spot-level profiles without accompanying spot-type labels, forcing biologists into labor-intensive manual annotation. Although large language models (LLMs) promise automated annotation, they are poorly equipped to handle high-dimensional numeric inputs, struggle to convert complex spatial-omics structures into interpretable text, and lack the specialized biological knowledge needed to avoid hallucinations. Moreover, the intrinsic sparsity and heterogeneity of spatial omics data undermine robust feature extraction and accurate spot-level niche label assignment. To address these challenges, we propose SpotTypeLLM, a framework for annotating spatial multi-omics spot-level niche types using a Bi-view Retrieval-Augmented Generation (BiRAG) tailored for LLMs. Specifically, SpotTypeLLM encodes spatial multi-omics data through scLLM-based embeddings, graph convolutional networks (GCNs), and multi-view attention module, and then selects spot-specific genes to construct the prompts for LLMs. We validate the accuracy and practical utility of our framework by comparing it with ten state-of-the-art methods on labeled spatial multi-omics datasets. The results demonstrate the effectiveness of SpotTypeLLM in overcoming the limitations of current annotation methods and enhancing spatial multi-omics analysis.