Contrastively generative self-expression model for single-cell and spatial multimodal data.

Advances in single-cell multi-omics technology provide an unprecedented opportunity to fully understand cellular heterogeneity. However, integrating omics data from multiple modalities is challenging due to the individual characteristics of each measurement. Here, to solve such a problem, we propose a contrastive and generative deep self-expression model, called single-cell multimodal self-expressive integration (scMSI), which integrates the heterogeneous multimodal data into a unified manifold space. Specifically, scMSI first learns each omics-specific latent representation and self-expression relationship to consider the characteristics of different omics data by deep self-expressive generative model. Then, scMSI combines these omics-specific self-expression relations through contrastive learning. In such a way, scMSI provides a paradigm to integrate multiple omics data even with weak relation, which effectively achieves the representation learning and data integration into a unified framework. We demonstrate that scMSI provides a cohesive solution for a variety of analysis tasks, such as integration analysis, data denoising, batch correction and spatial domain detection. We have applied scMSI on various single-cell and spatial multimodal datasets to validate its high effectiveness and robustness in diverse data types and application scenarios.