Multi-modal Spatial Clustering for Spatial Transcriptomics Utilizing High-resolution Histology Images

Abstract: Understanding the intricate cellular environment within biological tissues is crucial for uncovering insights into complex biological functions. While single-cell RNA sequencing has significantly enhanced our understanding of cellular states, it lacks the spatial context necessary to fully comprehend the cellular environment. Spatial transcriptomics (ST) addresses this limitation by enabling transcriptome-wide gene expression profiling while preserving spatial context. One of the principal challenges in ST data analysis is spatial clustering, which reveals spatial domains based on the spots within a tissue. Modern ST sequencing procedures typically include a high-resolution histology image, which has been shown in previous studies to be closely connected to gene expression profiles. However, current spatial clustering methods often fail to fully integrate high-resolution histology image features with gene expression data, limiting their ability to capture critical spatial and cellular interactions. In this study, we propose the spatial transcriptomics multi-modal clustering (stMMC) model, a novel contrastive learning-based deep learning approach that integrates gene expression data with histology image features through a multi-modal parallel graph autoencoder. We tested stMMC against four state-of-the-art baseline models: Leiden, GraphST, SpaGCN, and stLearn on two public ST datasets with 13 sample slices in total. The experiments demonstrated that stMMC outperforms all the baseline models in terms of ARI and NMI. An ablation study further validated the contributions of contrastive learning and the incorporation of histology image features.