SRLST: a unified multimodal representation learning framework for spatial transcriptomics analysis.

Abstract

Spatial transcriptomics (ST) enables molecular profiling within native tissue architecture, yet accurate delineation of spatial domains in ST data is challenging, as it demands the coordinated integration of transcriptomic, spatial, and tissue histological information. We present SRLST, an unsupervised representation learning framework that holistically harmonize these three complementary data modalities to precisely uncover tissue organization. SRLST employs a dual-graph variational autoencoding strategy to jointly model spatial proximity and morphological relations, fusing these with gene-expression embeddings into a unified latent space. Across distinct experimental datasets, SRLST consistently outperforms existing methods in delineating cortical organization, identifying small discontinuous tissue compartments, and capturing complex intratumor heterogeneity. The code implementation of the SRLST algorithm is available at https://github.com/lanbiolab/SRLST.