SCHNEL: Scalable clustering of high dimensional single-cell data

bioRxiv (Cold Spring Harbor Laboratory)

Abstract

Abstract Motivation Single cell data measures multiple cellular markers at the single-cell level for thousands to millions of cells. Identification of distinct cell populations is a key step for further biological understanding, usually performed by clustering this data. Dimensionality reduction based clustering tools are either not scalable to large datasets containing millions of cells, or not fully automated requiring an initial manual estimation of the number of clusters. Graph clustering tools provide automated and reliable clustering for single cell data, but suffer heavily from scalability to large datasets. Results We developed SCHNEL, a scalable, reliable and automated clustering tool for high-dimensional single-cell data. SCHNEL transforms large high-dimensional data to a hierarchy of datasets containing subsets of data points following the original data manifold. The novel approach of SCHNEL combines this hierarchical representation of the data with graph clustering, making graph clustering scalable to millions of cells. Using seven different cytometry datasets, SCHNEL outperformed three popular clustering tools for cytometry data, and was able to produce meaningful clustering results for datasets of 3.5 and 17.2 million cells within workable timeframes. In addition, we show that SCHNEL is a general clustering tool by applying it to single-cell RNA sequencing data, as well as a popular machine learning benchmark dataset MNIST. Availability and Implementation Implementation is available on GitHub ( https://github.com/paulderaadt/HSNE-clustering ) Contact a.mahfouz@lumc.nl Supplementary information Supplementary data are available at Bioinformatics online.

Authors 5

1. Tamim Abdelaal Aachen Leiden Computational Biology Center

   Leiden University Medical Center · Delft University of Technology

   Affiliation as printed

   Delft Bioinformatics Lab, Delft University of Technology, 2628 XE Delft, The Netherlands

   Leiden Computational Biology Center, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands

   Leiden Computational Biology Center, Leiden University Medical Center, 333 ZC Leiden, The Netherlands

2. Paul de Raadt Aachen Leiden Computational Biology Center

   Leiden University Medical Center

   Affiliation as printed

   Leiden Computational Biology Center, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands

   Leiden Computational Biology Center, Leiden University Medical Center, 333 ZC Leiden, The Netherlands

3. Boudewijn P. F. Lelieveldt Aachen Leiden Computational Biology Center

   Leiden University Medical Center · Delft University of Technology

   Affiliation as printed

   Delft Bioinformatics Lab, Delft University of Technology, 2628 XE Delft, The Netherlands

   Leiden Computational Biology Center, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands

   Leiden Computational Biology Center, Leiden University Medical Center, 333 ZC Leiden, The Netherlands

4. Marcel J. T. Reinders Aachen Department of Human Genetics Leiden Computational Biology Center

   Leiden University Medical Center · Delft University of Technology

   Affiliation as printed

   Delft Bioinformatics Lab, Delft University of Technology, 2628 XE Delft, The Netherlands

   Department of Human Genetics, Leiden University Medical Center, Leiden 2333ZC, The Netherlands

   Leiden Computational Biology Center, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands

   Department of Human Genetics, Leiden University Medical Center, Leiden 2ZC, The Netherlands

   Leiden Computational Biology Center, Leiden University Medical Center, 333 ZC Leiden, The Netherlands

5. Ahmed Essam Mahfouz corresponding Aachen Department of Human Genetics Leiden Computational Biology Center

   Leiden University Medical Center · Delft University of Technology

   Affiliation as printed

   Delft Bioinformatics Lab, Delft University of Technology, 2628 XE Delft, The Netherlands

   Department of Human Genetics, Leiden University Medical Center, Leiden 2333ZC, The Netherlands

   Leiden Computational Biology Center, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands

   Department of Human Genetics, Leiden University Medical Center, Leiden 2ZC, The Netherlands

   Leiden Computational Biology Center, Leiden University Medical Center, 333 ZC Leiden, The Netherlands