Joint learning dimension reduction and clustering of single-cell RNA-sequencing data.

Abstract

Single-cell RNA-sequencing (scRNA-seq) profiles transcriptome of individual cells, which enables the discovery of cell types or subtypes by using unsupervised clustering. Current algorithms perform dimension reduction before cell clustering because of noises, high-dimensionality and linear inseparability of scRNA-seq data. However, independence of dimension reduction and clustering fails to fully characterize patterns in data, resulting in an undesirable performance. In this study, we propose a flexible and accurate algorithm for scRNA-seq data by jointly learning dimension reduction and cell clustering (aka DRjCC), where dimension reduction is performed by projected matrix decomposition and cell type clustering by non-negative matrix factorization. We first formulate joint learning of dimension reduction and cell clustering into a constrained optimization problem and then derive the optimization rules. The advantage of DRjCC is that feature selection in dimension reduction is guided by cell clustering, significantly improving the performance of cell type discovery. Eleven scRNA-seq datasets are adopted to validate the performance of algorithms, where the number of single cells varies from 49 to 68579 with the number of cell types ranging from 3 to 14. The experimental results demonstrate that DRjCC significantly outperforms 13 state-of-the-art methods in terms of various measurements on cell type clustering (on average 17.44% by improvement). Furthermore, DRjCC is efficient and robust across different scRNA-seq datasets from various tissues. The proposed model and methods provide an effective strategy to analyze scRNA-seq data. The software is coded using matlab, and is free available for academic https://github.com/xkmaxidian/DRjCC. Supplementary data are available at Bioinformatics online.