Visual analysis of mass cytometry data by hierarchical stochastic neighbour embedding reveals rare cell types

  • Vincent van Unen (Corresponding author)
  • , Thomas Höllt
  • , Nicola Pezzotti
  • , Na Li
  • , Marcel J.T. Reinders
  • , Elmar Eisemann
  • , Frits Koning (Corresponding author)
  • , Anna Vilanova
  • , Boudewijn P.F. Lelieveldt

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Mass cytometry allows high-resolution dissection of the cellular composition of the immune system. However, the high-dimensionality, large size, and non-linear structure of the data poses considerable challenges for the data analysis. In particular, dimensionality reduction-based techniques like t-SNE offer single-cell resolution but are limited in the number of cells that can be analyzed. Here we introduce Hierarchical Stochastic Neighbor Embedding (HSNE) for the analysis of mass cytometry data sets. HSNE constructs a hierarchy of non-linear similarities that can be interactively explored with a stepwise increase in detail up to the single-cell level. We apply HSNE to a study on gastrointestinal disorders and three other available mass cytometry data sets. We find that HSNE efficiently replicates previous observations and identifies rare cell populations that were previously missed due to downsampling. Thus, HSNE removes the scalability limit of conventional t-SNE analysis, a feature that makes it highly suitable for the analysis of massive high-dimensional data sets.

Original languageEnglish
Article number1740
Number of pages10
JournalNature Communications
Volume8
Issue number1
DOIs
Publication statusPublished - 23 Nov 2017
Externally publishedYes

Funding

The research leading to these results has received funding from Leiden University Medical Center, the Netherlands Organization for Scientific Research (ZonMW grant 91112008) and the Technology Foundation STW, the Netherlands (VAnPIRe; grant 12720, and Genes in Space; grant 12721). We thank Drs M.W. Schilham, M. Yazdan-bakhsh, J. Goeman, K. Schepers, J. van Bergen and S.E. de Jong for critical review of the manuscript and B. van Lew for narrating the Supplementary Movie 1.

Keywords

  • Algorithms
  • Antigens, CD/metabolism
  • Biomarkers/metabolism
  • CD4-Positive T-Lymphocytes/classification
  • Cytological Techniques/statistics & numerical data
  • Databases, Factual
  • Flow Cytometry/statistics & numerical data
  • Gastrointestinal Diseases/immunology
  • Humans
  • Image Cytometry/statistics & numerical data
  • Lymphocytes/immunology
  • Single-Cell Analysis/statistics & numerical data
  • Stochastic Processes
  • T-Lymphocyte Subsets/classification

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