Recent advancements in methodologies and technologies have enabled the simultaneous measurement of multiple omics data, which provides a comprehensive understanding of cellular heterogeneity. However, existing methods have limitations in accurately identifying cell types while maintaining model interpretability, especially in the presence of noise. We propose a novel method called scMFG, which leverages feature grouping and group integration techniques for the integration of single-cell multi-omics data. By organizing features with similar characteristics within each omics layer through feature grouping. Furthermore, scMFG ensures a consistent feature grouping approach across different omics layers, promoting comparability of diverse data types. Additionally, scMFG incorporates a matrix factorization-based approach to enable the integrated results remain interpretable. We comprehensively evaluated scMFG’s performance on four complex real-world datasets generated using diverse sequencing technologies, highlighting its robustness in accurately identifying cell types. Notably, scMFG exhibited superior performance in deciphering cellular heterogeneity at a finer resolution compared to existing methods when applied to simulated datasets. Furthermore, our method proved highly effective in identifying rare cell types, showcasing its robust performance and suitability for detecting low-abundance cellular populations. The interpretability of scMFG was successfully validated through its specific association of outputs with specific cell types or states observed in the neonatal mouse cerebral cortices dataset. Moreover, we demonstrated that scMFG is capable of identifying cell developmental trajectories even in datasets with batch effects. Our work presents a robust framework for the analysis of single-cell multi-omics data, advancing our understanding of cellular heterogeneity in a comprehensive and interpretable manner.
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