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

• Type of Material: Article
• Authors: Darya Y. Orlova, Stanford University; Noah Zimmerman, Stanford University; Stephen Meehan, Stanford University; Connor Meehan, California Institute of Technology; Jeffrey Waters, Stanford University; Eliver Ghosn, Emory University; Alexande Filatenkov, Stanford University; Gleb A. Kolyagin, Independent Researcher; Yael Gernez, Stanford University; Shanel Tsuda, Stanford University; Wayne Moore, Stanford University; Richard B. Moss, Stanford University; Leonore A. Herzenberg, Stanford University; Guenther Walther, Stanford University
• Language: English
• Date: 2016-03-23
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2016 Orlova et al
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0151859
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 11
• Issue: 3
• Start Page: e0151859
• End Page: e0151859
• Grant/Funding Information: Funding provided by National Science Foundation, http://www.nsf.gov/, Award Number: DMS-1220311, Grant Recipient: GW, National Institute of Allergy and Infectious Diseases, https://www.niaid.nih.gov/Pages/default.aspx, Award Number: 098519, Grant Recipient: LH and National Institutes of Health, Award Number: 5 T32 AI07290, Grant Recipient: DO.
• Keywords: HISTOGRAMS; DIFFERENCE; Multidisciplinary Sciences; Science & Technology - Other Topics; MICE; CYSTIC-FIBROSIS; ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS; Science & Technology; SUBSETS; FLOW-CYTOMETRY DATA; DISTRIBUTIONS
• Research Categories: Biology, Genetics; Health Sciences, Immunology

Abstract

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.