ARGLRR: A Sparse Low-Rank Representation Single-Cell RNA-Sequencing Data Clustering Method Combined with a New Graph Regularization.

Abstract

The development of single-cell transcriptome sequencing technologies has opened new ways to study biological phenomena at the cellular level. A key application of such technologies involves the employment of single-cell RNA sequencing (scRNA-seq) data to identify distinct cell types through clustering, which in turn provides evidence for revealing heterogeneity. Despite the promise of this approach, the inherent characteristics of scRNA-seq data, such as higher noise levels and lower coverage, pose major challenges to existing clustering methods and compromise their accuracy. In this study, we propose a method called Adjusted Random walk Graph regularization Sparse Low-Rank Representation (ARGLRR), a practical sparse subspace clustering method, to identify cell types. The fundamental low-rank representation (LRR) model is concerned with the global structure of data. To address the limited ability of the LRR method to capture local structure, we introduced adjusted random walk graph regularization in its framework. ARGLRR allows for the capture of both local and global structures in scRNA-seq data. Additionally, the imposition of similarity constraints into the LRR framework further improves the ability of the proposed model to estimate cell-to-cell similarity and capture global structural relationships between cells. ARGLRR surpasses other advanced comparison approaches on nine known scRNA-seq data sets judging by the results. In the normalized mutual information and Adjusted Rand Index metrics on the scRNA-seq data sets clustering experiments, ARGLRR outperforms the best-performing comparative method by 6.99% and 5.85%, respectively. In addition, we visualize the result using Uniform Manifold Approximation and Projection. Visualization results show that the usage of ARGLRR enhances the separation of different cell types within the similarity matrix.