New single-cell technologies continue to fuel the explosive growth in the scale of heterogeneous single-cell data. However, existing computational methods are inadequately scalable to large datasets and therefore cannot uncover the complex cellular heterogeneity.

We introduce a highly scalable graph-based clustering algorithm PARC—Phenotyping by Accelerated Refined Community-partitioning—for large-scale, high-dimensional single-cell data (>1 million cells). Using large single-cell flow and mass cytometry, RNA-seq and imaging-based biophysical data, we demonstrate that PARC consistently outperforms state-of-the-art clustering algorithms without subsampling of cells, including Phenograph, FlowSOM and Flock, in terms of both speed and ability to robustly detect rare cell populations. For example, PARC can cluster a single-cell dataset of 1.1 million cells within 13 min, compared with >2 h for the next fastest graph-clustering algorithm. Our work presents a scalable algorithm to cope with increasingly large-scale single-cell analysis.

https://github.com/ShobiStassen/PARC.

Supplementary data are available at Bioinformatics online.