Recover then aggregate: unified cross-modal deep clustering with global structural information for single-cell data.

Abstract

Single-cell cross-modal joint clustering has been extensively utilized to investigate the tumor microenvironment. Although numerous approaches have been suggested, accurate clustering remains the main challenge. First, the gene expression matrix frequently contains numerous missing values due to measurement limitations. The majority of existing clustering methods treat it as a typical multi-modal dataset without further processing. Few methods conduct recovery before clustering and do not sufficiently engage with the underlying research, leading to suboptimal outcomes. Additionally, the existing cross-modal information fusion strategy does not ensure consistency of representations across different modes, potentially leading to the integration of conflicting information, which could degrade performance. To address these challenges, we propose the 'Recover then Aggregate' strategy and introduce the Unified Cross-Modal Deep Clustering model. Specifically, we have developed a data augmentation technique based on neighborhood similarity, iteratively imposing rank constraints on the Laplacian matrix, thus updating the similarity matrix and recovering dropout events. Concurrently, we integrate cross-modal features and employ contrastive learning to align modality-specific representations with consistent ones, enhancing the effective integration of diverse modal information. Comprehensive experiments on five real-world multi-modal datasets have demonstrated this method's superior effectiveness in single-cell clustering tasks.