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

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. © 2018 International Society for Advancement of Cytometry.

SUBMITTER: Erez A

PROVIDER: S-EPMC7983168 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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

Erez Amir A Vogel Robert R Mugler Andrew A Belmonte Andrew A Altan-Bonnet Grégoire G

Cytometry. Part A : the journal of the International Society for Analytical Cytology 20180216 6

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 under ...[more]

PMID: 29451717

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

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

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