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

Author:

Zhang Chengming123ORCID,Yang Yiwen124,Tang Shijie12,Aihara Kazuyuki3,Zhang Chuanchao567ORCID,Chen Luonan124897ORCID

Affiliation:

1. Key Laboratory of Systems Biology , Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, , Shanghai 200031 , China

2. Chinese Academy of Sciences , Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, , Shanghai 200031 , China

3. International Research Center for Neurointelligence, The University of Tokyo Institutes for Advanced Study , The University of Tokyo, Tokyo 113-0033 , Japan

4. School of Life Science and Technology, ShanghaiTech University , Shanghai 201210 , China

5. Key Laboratory of Systems Health Science of Zhejiang Province , Hangzhou Institute for Advanced Study, University of , Hangzhou 310024 , China

6. Chinese Academy of Sciences, Chinese Academy of Sciences , Hangzhou Institute for Advanced Study, University of , Hangzhou 310024 , China

7. Guangdong Institute of Intelligence Science and Technology , Hengqin, Zhuhai, Guangdong 519031 , China

8. Key Laboratory of Systems Health Science of Zhejiang Province , Hangzhou Institute for Advanced Study, , Chinese Academy of Sciences, Hangzhou 310024 , China

9. University of Chinese Academy of Sciences , Hangzhou Institute for Advanced Study, , Chinese Academy of Sciences, Hangzhou 310024 , China

Abstract

Abstract 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.

Funder

National Basic Research Program of China

Strategic Priority Research Program of the Chinese Academy of Sciences

National Natural Science Foundation of China

Special Fund for Science and Technology Innovation Strategy of Guangdong Province

Japan Science and Technology Agency

AMED

Institute of AI and Beyond of the University of Tokyo

International Research Center for Neurointelligence

University of Tokyo Institutes for Advanced Study

Japan Society for the Promotion of Science

Publisher

Oxford University Press (OUP)

Subject

Molecular Biology,Information Systems

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