scCAT: Single-cell Combined graph Attentional clustering for scRNA-seq analysis

Abstract

The advent of single-cell RNA sequencing (scRNA-seq) has revolutionized gene expression research at the single-cell level, enabling the study of cellular heterogeneity and identification of rare cell populations. Deep clustering is crucial for analyzing scRNA-seq datasets by assigning cells into subpopulations. However, inherent sparsity and variability in gene expression pose challenges to clustering accuracy. To address these issues, a novel unsupervised deep clustering approach named single-cell Combined graph Attentional clustering (scCAT) is introduced. The method designs a dual-branch joint dimensionality reduction (JDR) module to learn gene expression. This strategy preserves key variance while capturing complex nonlinear relationships, effectively addressing the high-dimensionality challenges of single-cell data. Additionally, a Zero-inflated negative binomial (ZINB) distribution is integrated within the JDR to tackle significant noise, sparsity, and zero-inflation challenges. A graph attention autoencoder (GATE) then processes the graph-structured data, enhancing the integration of integrating cellular topological relationships and gene expressions. Finally, a k-means-based self-optimization technique refines clustering while synchronizing with representation learning. Experimental evaluations on eight scRNA-seq datasets demonstrate that scCAT significantly improves clustering performance, mitigates the impact of inherent data defects. The embeddings learned from both linear and non-linear perspectives eliminate inter-component interactions, uncovering complex underlying structures and enhancing the recognition of cellular topological relationships when combined with graph neural networks.