title: Earth Mover's Distance (EMD): A True Metric for Comparing Biomarker Expression Levels in Cell Populations.
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.
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Darya Y
authors.initials: DY
authors.lastname: Orlova
authors.affiliation: Department of Statistics, Stanford University, Stanford, California, United States of America.
authors.forename: Noah
authors.initials: N
authors.lastname: Zimmerman
authors.affiliation: Department of Statistics, Stanford University, Stanford, California, United States of America.
authors.forename: Stephen
authors.initials: S
authors.lastname: Meehan
authors.affiliation: Department of Mathematics, California Institute of Technology, Pasadena, California, United States of America.
authors.forename: Connor
authors.initials: C
authors.lastname: Meehan
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Waters
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Eliver E B
authors.initials: EE
authors.lastname: Ghosn
authors.affiliation: Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Alexander
authors.initials: A
authors.lastname: Filatenkov
authors.affiliation: Independent Researcher, Menlo Park, California, United States of America.
authors.forename: Gleb A
authors.initials: GA
authors.lastname: Kolyagin
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California, United States of America.|Department of Allergy and Immunology, Mount Sinai Hospital, New York, New York, United States of America.
authors.forename: Yael
authors.initials: Y
authors.lastname: Gernez
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Shanel
authors.initials: S
authors.lastname: Tsuda
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Wayne
authors.initials: W
authors.lastname: Moore
authors.affiliation: Center for Excellence in Pulmonary Biology, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Moss
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Leonore A
authors.initials: LA
authors.lastname: Herzenberg
authors.affiliation: Department of Statistics, Stanford University, Stanford, California, United States of America.
authors.forename: Guenther
authors.initials: G
authors.lastname: Walther
mesh_terms: D000465:Algorithms; D015415:Biomarkers / Q000378:metabolism*; D005434:Flow Cytometry; D011336:Probability
chemical_list: D015415:Biomarkers