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SAFE-clustering: Single-cell Aggregated (From Ensemble) Clustering for Single-cell RNA-seq Data

By Yuchen Yang, Ruth Huh, Houston W. Culpepper, Yuan Lin, Michael I. Love, Yun Li

Posted 07 Nov 2017
bioRxiv DOI: 10.1101/215723 (published DOI: 10.1093/bioinformatics/bty793)

Motivation: Accurately clustering cell types from a mass of heterogeneous cells is a crucial first step for the analysis of single-cell RNA-seq (scRNA-Seq) data. Although several methods have been recently developed, they utilize different characteristics of data and yield varying results in terms of both the number of clusters and actual cluster assignments. Results: Here, we present SAFE-clustering, Single-cell Aggregated (From Ensemble) clustering, a flexible, accurate and robust method for clustering scRNA-Seq data. SAFE-clustering takes as input, results from multiple clustering methods, to build one consensus solution. SAFE-clustering currently embeds four state-of-the-art methods, SC3, CIDR, Seurat and t-SNE + k-means; and ensembles solutions from these four methods using three hypergraph-based partitioning algorithms. Extensive assessment across 12 datasets with the number of clusters ranging from 3 to 14, and the number of single cells ranging from 49 to 32,695 showcases the advantages of SAFE-clustering in terms of both cluster number (18.9 - 50.0% reduction in absolute deviation to the truth) and cluster assignment (on average 28.9% improvement, and up to 34.5% over the best of the four methods, measured by adjusted rand index). Moreover, SAFE-clustering is computationally efficient to accommodate large datasets, taking <10 minutes to process 28,733 cells. Availability and implementation: SAFE-clustering, including source codes and tutorial, is free available on the web at http://yunliweb.its.unc.edu/safe/.

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