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scSiameseClu: A Siamese Clustering Framework for Interpreting single-cell RNA Sequencing Data

2025/05/19 by Ping Xu, Xu, Ping, Zhiyuan Ning +13 · 3 citations
Biochemistry, Genetics and Molecular Biology · Computer Science · #Artificial Intelligence (cs.AI) #Bioinformatics and Genomic Networks #Domain Adaptation and Few-Shot Learning #FOS: Biological sciences #FOS: Computer and information sciences #Genomics (q-bio.GN) #Machine Learning (cs.LG) #Single-cell and spatial transcriptomics

paper · pdf · doi:10.48550/arxiv.2505.12626

openalex publication_date 2025/05/19 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28

Abstract

Single-cell RNA sequencing (scRNA-seq) reveals cell heterogeneity, with cell clustering playing a key role in identifying cell types and marker genes. Recent advances, especially graph neural networks (GNNs)-based methods, have significantly improved clustering performance. However, the analysis of scRNA-seq data remains challenging due to noise, sparsity, and high dimensionality. Compounding these challenges, GNNs often suffer from over-smoothing, limiting their ability to capture complex biological information. In response, we propose scSiameseClu, a novel Siamese Clustering framework for interpreting single-cell RNA-seq data, comprising of 3 key steps: (1) Dual Augmentation Module, which applies biologically informed perturbations to the gene expression matrix and cell graph relationships to enhance representation robustness; (2) Siamese Fusion Module, which combines cross-correlation refinement and adaptive information fusion to capture complex cellular relationships while mitigating over-smoothing; and (3) Optimal Transport Clustering, which utilizes Sinkhorn distance to efficiently align cluster assignments with predefined proportions while maintaining balance. Comprehensive evaluations on seven real-world datasets demonstrate that scSiameseClu outperforms state-of-the-art methods in single-cell clustering, cell type annotation, and cell type classification, providing a powerful tool for scRNA-seq data interpretation.

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