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Earth Mover’s Distance (EMD): A True Metric for Comparing Biomarker Expression Levels in Cell Populations

Orlova, Darya Y. and Zimmerman, Noah and Meehan, Stephen and Meehan, Connor and Waters, Jeffrey and Ghosn, Eliver E. B. and Filatenkov, Alexander and Kolyagin, Gleb A. and Gernez, Yael and Tsuda, Shanel and Moore, Wayne and Moss, Richard B. and Herzenberg, Leonore A. and Walther, Guenther (2016) Earth Mover’s Distance (EMD): A True Metric for Comparing Biomarker Expression Levels in Cell Populations. PLoS ONE, 11 (3). Art. No. e0151859. ISSN 1932-6203. PMCID PMC4805242. doi:10.1371/journal.pone.0151859.

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Changes in the frequencies of cell subsets that (co)express characteristic biomarkers, or levels of the biomarkers on the subsets, are widely used as indices of drug response, disease prognosis, stem cell reconstitution, etc. However, although the currently available computational “gating” tools accurately reveal subset frequencies and marker expression levels, they fail to enable statistically reliable judgements as to whether these frequencies and expression levels differ significantly between/among subject groups. Here we introduce flow cytometry data analysis pipeline which includes the Earth Mover’s Distance (EMD) metric as solution to this problem. Well known as an informative quantitative measure of differences between distributions, we present three exemplary studies showing that EMD 1) reveals clinically-relevant shifts in two markers on blood basophils responding to an offending allergen; 2) shows that ablative tumor radiation induces significant changes in the murine colon cancer tumor microenvironment; and, 3) ranks immunological differences in mouse peritoneal cavity cells harvested from three genetically distinct mouse strains.

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Additional Information:© 2016 Orlova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received: December 1, 2015; Accepted: March 4, 2016; Published: March 23, 2016. Data Availability: Data are available from FlowRepository (,,, Funding provided by National Science Foundation,, Award Number: DMS-1220311, Grant Recipient: GW, National Institute of Allergy and Infectious Diseases,, Award Number: 098519, Grant Recipient: LH and National Institutes of Health, Award Number: 5 T32 AI07290, Grant Recipient: DO. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have declared that no competing interests exist. We thank the members of the Herzenberg laboratory for advice and help in the interpretation of flow cytometry data, and we thank John Mantovani for administrative help. Author Contributions: Conceived and designed the experiments: JW EEBG AF YG RBM LAH. Performed the experiments: JW EEBG AF YG. Analyzed the data: DYO NZ SM CM JW EEBG AF GAK YG ST WM RBM LAH GW. Contributed reagents/materials/analysis tools: DYO NZ SM AF GAK WM RBM LAH GW. Wrote the paper: DYO NZ SM CM JW EEBG AF GAK YG ST WM RBM LAH GW. Conception and design of the analysis methods and software used in analysis: DYO NZ SM CM GAK WM LAH GW.
Funding AgencyGrant Number
NIH Predoctoral Fellowship5 T32 AI07290
Issue or Number:3
PubMed Central ID:PMC4805242
Record Number:CaltechAUTHORS:20160329-081010385
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Official Citation:Orlova DY, Zimmerman N, Meehan S, Meehan C, Waters J, Ghosn EEB, et al. (2016) Earth Mover’s Distance (EMD): A True Metric for Comparing Biomarker Expression Levels in Cell Populations. PLoS ONE 11(3): e0151859. doi:10.1371/journal.pone.0151859
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:65725
Deposited By: Tony Diaz
Deposited On:29 Mar 2016 17:59
Last Modified:10 Nov 2021 23:49

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