scMCs: a framework for single-cell multi-omics data integration and multiple clusterings

Abstract Motivation The integration of single-cell multi-omics data can uncover the underlying regulatory basis of diverse cell types and states. However, contemporary methods disregard the omics individuality, and the high noise, sparsity, and heterogeneity of single-cell data also impact the fusion effect. Furthermore, available single-cell clustering methods only focus on the cell type clustering, which cannot mine the alternative clustering to comprehensively analyze cells. Results We propose a single-cell data fusion based multiple clustering (scMCs) approach that can jointly model single-cell transcriptomics and epigenetic data, and explore multiple different clusterings. scMCs first mines the omics-specific and cross-omics consistent representations, then fuses them into a co-embedding representation, which can dissect cellular heterogeneity and impute data. To discover the potential alternative clustering embedded in multi-omics, scMCs projects the co-embedding representation into different salient subspaces. Meanwhile, it reduces the redundancy between subspaces to enhance the diversity of alternative clusterings and optimizes the cluster centers in each subspace to boost the quality of corresponding clustering. Unlike single clustering, these alternative clusterings provide additional perspectives for understanding complex genetic information, such as cell types and states. Experimental results show that scMCs can effectively identify subcellular types, impute dropout events, and uncover diverse cell characteristics by giving different but meaningful clusterings. Availability and implementation The code is available at www.sdu-idea.cn/codes.php?name=scMCs.