Learning to Cluster Rare Cell Types: Implicit Semantic Data Augmentation for Spatial Multi-modal Omics Analysis

Abstract Spatial multi-modal omics technologies have transformed biological research by enabling the simultaneous profiling of gene expression, protein abundance, and chromatin accessibility within their native spatial contexts. Despite these advances, accurately clustering rare cell types remains a major challenge due to data sparsity, high dimensionality, and limited annotated samples. While Graph Neural Networks (GNNs) have shown potential in modeling spatial omics data, their effectiveness is often constrained by the use of fixed K-nearest neighbor (KNN) graph structures, which fail to capture latent semantic relationships masked by sequencing noise. To overcome these limitations, we propose CRCT (Clustering Rare Cell Types): a novel framework that combines Implicit Semantic Data Augmentation (ISDA) with adaptive graph learning for spatial multi-modal omics analysis. Unlike traditional augmentation strategies that generate explicit synthetic samples, CRCT operates in the deep feature space by dynamically estimating intra-class covariance matrices and implicitly perturbing features along semantically meaningful directions. This enables effective augmentation for rare cell populations while preserving biological fidelity. Extensive experiments across four real-world datasets (HLN, MB, Stereo‑CITE‑seq, and SPOTS) and one synthetic benchmark demonstrate the state-of-the-art performance of CRCT, achieving improvements of up to +1.7 NMI and +7.8 ARI over strong baseline methods.