GRACE: A Graph-Based Cluster Ensemble Approach for Single-Cell RNA-Seq Data Clustering

Abstract

Rapid development of single cell RNA sequencing (scRNA-seq) technology has accelerated the exploration in biomedical researches. One of the focal interests in scRNA-seq data analysis is to classify cells into different types, which significantly assists in studying inter-cellular heterogeneity, such as cell types, cell states, and cell lineages, at the resolution of single cells. Although a number of tailored approaches have been developed for scRNA-seq data, their performance varies with different datasets and their clustering accuracy need to be improved. In this paper, we propose a novel ensemble clustering framework for scRNA-seq data called GRACE (GRAph-based Cluster Ensemble approach). First, we construct a highly reliable graph network for single cells by combining the clustering outcomes from five leading scRNA-seq data clustering methods. Then, we remeasure the relationships between cells by exploring the topology structure of network using random walk distance. Finally, we build a hierarchical cell-tree and obtain the clustering labels by cutting the tree structure into an appropriate number of sub-trees. Experimental results on twelve benchmark datasets show that GRACE has the higher clustering accuracy and is more robust among a variety of datasets than the state-of-the-art individual approaches. In addition, the graph structure of the network which is built upon the ensemble clusters is more reliable than the networks which are constructed according to the conventional similarity metrics.

Keywords

• Single cell {RNA-seq} data
• ensemble cluster
• random walk distance
• graph theory
• hierarchical clustering