Single-cell data integration across weakly linked modalities.

Rapid advancements in technology enables the measurement of multimodal data at single-cell resolution, but with emerging modalities that are characterized by weak correlations with other modalities. Several computational approaches attempt to integrate these weakly linked multimodal data, but face challenges regarding accurate modeling relationship between cells and learning meaningful cell representation. In this study, single-cell MultiModal data Integration through Hypergraph Contrastive Learning (MMIHCL), a deep learning-based framework that leverages an optimized adaptive k-nearest neighbor graph to model single cell pair-wise relationships for multimodal data integration is presented. MMIHCL uses hypergraph contrastive learning to capture the high-order information of a graph to produce cell representations. Comprehensive benchmarking using a multi-dimensional evaluation framework demonstrates that MMIHCL consistently delivers high-quality integration across diverse weakly linked datasets and maintains high accuracy in strongly linked scenarios. Crucially, MMIHCL exhibits versatile utility in downstream applications: it enables accurate cross-modality feature prediction via explicit cell matching, and empowers robust disease classification and drug target discovery by leveraging optimized joint embeddings. A python implementation of MMIHCL is publicly available at https://github.com/SundayChou/MMIHCL.