Modeling of cytometry data in logarithmic space: When is a bimodal distribution not bimodal?

Amir Erez, Robert Vogel, Andrew Mugler, Andrew Belmonte, Grégoire Altan-Bonnet

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Recent efforts in systems immunology lead researchers to build quantitative models of cell activation and differentiation. One goal is to account for the distributions of proteins from single-cell measurements by flow cytometry or mass cytometry as readout of biological regulation. In that context, large cell-to-cell variability is often observed in biological quantities. We show here that these readouts, viewed in logarithmic scale may result in two easily-distinguishable modes, while the underlying distribution (in linear scale) is unimodal. We introduce a simple mathematical test to highlight this mismatch. We then dissect the flow of influence of cell-to-cell variability proposing a graphical model which motivates higher-dimensional analysis of the data. Finally we show how acquiring additional biological information can be used to reduce uncertainty introduced by cell-to-cell variability, helping to clarify whether the data is uni- or bimodal. This communication has cautionary implications for manual and automatic gating strategies, as well as clustering and modeling of single-cell measurements.

Original languageEnglish (US)
Pages (from-to)611-619
Number of pages9
JournalCytometry Part A
Volume93
Issue number6
DOIs
StatePublished - Jun 2018

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

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