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

• Published in: PloS one Vol. 11; no. 3; p. e0151859
• Main Authors: Orlova, Darya Y., Zimmerman, Noah, Meehan, Stephen, Meehan, Connor, Waters, Jeffrey, Ghosn, Eliver E. B., Filatenkov, Alexander, Kolyagin, Gleb A., Gernez, Yael, Tsuda, Shanel, Moore, Wayne, Moss, Richard B., Herzenberg, Leonore A., Walther, Guenther
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.03.2016; Public Library of Science (PLoS)
• Subjects: Algorithms; Allergens; Allergies; Biological markers; Biology and Life Sciences; Biomarkers; Biomarkers - metabolism; Colon; Colon cancer; Colorectal cancer; Computer applications; Cystic fibrosis; Cytometry; Data analysis; Data processing; Development and progression; Flow Cytometry; Gating; Genetic aspects; Image retrieval; Immunology; Leukocytes (basophilic); Medicine; Medicine and Health Sciences; Peritoneum; Physiological aspects; Population; Probability; Radiation; Research and Analysis Methods; Software; Standard deviation; Statistics; Stem cells; United States
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0151859

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.