Similarity and Dissimilarity Regularized Nonnegative Matrix Factorization for Single-Cell RNA-seq Analysis

In traditional sequencing techniques, the different functions of cells and the different roles they play in differentiation are often ignored. With the advancement of single-cell RNA sequencing (scRNA-seq) techniques, scientists can measure the gene expression value at the single-cell level, and it is helping to understand the heterogeneity hidden in cells. One of the most powerful ways to find heterogeneity is using the unsupervised clustering method to get separate subpopulations. In this paper, we propose a novel clustering method Similarity and Dissimilarity Regularized Nonnegative Matrix Factorization (SDCNMF) that simultaneously impose similarity and dissimilarity constraints on low-dimensional representations. SDCNMF both considers the similarity of closer cells and the dissimilarity of cells that are farther away. It can not only keep the similar cells getting closer in low-dimensional space, but also can push the dissimilar cells away from each other. We test the validity of our proposed method on five scRNA-seq datasets. Clustering results show that SDCNMF is better than other comparative methods, and the gene markers we find are also consistent with previous studies. Therefore, we can conclude that SDCNMF is effective in scRNA-seq data analysis. Graphic abstract: This paper proposes a novel clustering method Similarity and Dissimilarity Regularized Nonnegative Matrix Factorization (SDCNMF) that simultaneously impose similarity and dissimilarity constraints on low-dimensional representations. SDCNMF both considers the similarity of closer cells and the dissimilarity of cells that are farther away. It can not only keep the similar cells getting closer in low-dimensional space, but also can push the dissimilar cells away from each other. Clustering results show that SDCNMF is better than other comparative methods, and the gene markers we find are also consistent with previous studies. [Figure not available: see fulltext.]