scDRMAE: integrating masked autoencoder with residual attention networks to leverage omics feature dependencies for...

Cell clustering is foundational for analyzing the heterogeneity of biological tissues using single-cell sequencing data. With the maturation of single-cell multi-omics sequencing technologies, we can integrate multiple omics data to perform cell clustering, thereby overcoming the limitations of insufficient information from single omics data. Existing methods for cell clustering often only consider the differences in data patterns during the analysis of multi-omics data, but the dependencies between omics features of different cell types also significantly influence cell clustering. Moreover, the high dropout rates in scRNA-seq and scATAC-seq data can impact the performance of cell clustering.

We propose a cell clustering model based on a masked autoencoder, scDRMAE. Utilizing a masking mechanism, scDRMAE effectively learns the relationships between different features and imputes false zeros caused by dropout events. To differentiate the importance of various omics data in cell clustering, we dynamically adjust the weights of different omics data through an attention mechanism. Finally, we use the K-means algorithm for cluster analysis of the fused multi-omics data. On commonly used sets of 15 multi-omics datasets, our method demonstrates superior cell clustering performance on multiple metrics compared to other computational methods. In addition, when datasets exhibit varying degrees of dropout noise, our method shows better performance and stronger stability on multiple metrics compared to other methods. Moreover, by analyzing the cell clusters classified by scDRMAE, we identified several biologically significant biomarkers that have been validated, further confirming the effectiveness of scDRMAE in cell clustering from a biological perspective.