Joint L_2,p-norm and random walk graph constrained PCA for single-cell RNA-seq data

Abstract

The development and widespread utilization of high-throughput sequencing technologies in biology has fueled the rapid growth of single-cell RNA sequencing (scRNA-seq) data over the past decade. The development of scRNA-seq technology has significantly expanded researchers’ understanding of cellular heterogeneity. Accurate cell type identification is the prerequisite for any research on heterogeneous cell populations. However, due to the high noise and high dimensionality of scRNA-seq data, improving the effectiveness of cell type identification remains a challenge. As an effective dimensionality reduction method, Principal Component Analysis (PCA) is an essential tool for visualizing high-dimensional scRNA-seq data and identifying cell subpopulations. However, traditional PCA has some defects when used in mining the nonlinear manifold structure of the data and usually suffers from over-density of principal components (PCs). Therefore, we present a novel method in this paper called joint $L_{2,p}$-norm and random walk graph constrained PCA (RWPPCA). RWPPCA aims to retain the data’s local information in the process of mapping high-dimensional data to low-dimensional space, to more accurately obtain sparse principal components and to then identify cell types more precisely. Specifically, RWPPCA combines the random walk (RW) algorithm with graph regularization to more accurately determine the local geometric relationships between data points. Moreover, to mitigate the adverse effects of dense PCs, the $L_{2,p}$-norm is introduced to make the PCs sparser, thus increasing their interpretability. Then, we evaluate the effectiveness of RWPPCA on simulated data and scRNA-seq data. The results show that RWPPCA performs well in cell type identification and outperforms other comparison methods.

Keywords:

• Cell type identification
• principal component analysis
• random walk graph regularization
• single-cell RNA sequencing data

Disclosure statement

There are no potential conflicts of interest reported by the authors.

Additional information

Funding

This work was supported by National Natural Science Foundation of China under Grant Nos. 62172253, 62172254, 61972226, and 61902216.