ST-LLM: Spatial Transcriptomics Embedding with Large Language Models

Abstract

Spatial transcriptomics provides unprecedented opportunities to analyze gene patterns while preserving spatial tissue architecture. However, traditional deep learning methods for spatial transcriptomics analysis face significant challenges in multi-modal data integration, spatial dependency modeling, and biological knowledge incorporation, while existing large language models lack explicit spatial modeling capabilities for transcriptomic data. So we first present a Spatial Transcriptomics Embedding with Large Language Models (ST-LLM), a novel simple and effective approach that transforms intricate spatial graph structures into structured textual representations suitable for large language models (LLMs). ST-LLM dynamically constructs graph adjacency construction using reinforcement learning paradigms to adaptively optimize spatial relationships, converts the resulting graphs into hierarchical textual descriptions with spatial context, and leverages pre-trained semantic understanding to generate high-dimensional spatial-aware representations. Comprehensive experiments on 14 datasets demonstrate that ST-LLM achieves comparable or better performance than traditional model. ST-LLM shows that LLMs embeddings provide a new simple and effective path to encoding spatial transcriptomics biological knowledge.