title: Systematic Analysis of Cell-to-Cell Expression Variation of T Lymphocytes in a Human Cohort Identifies Aging and Genetic Associations.
abstract: Cell-to-cell expression variation (CEV) is a prevalent feature of even well-defined cell populations, but its functions, particularly at the organismal level, are not well understood. Using single-cell data obtained via high-dimensional flow cytometry of T cells as a model, we introduce an analysis framework for quantifying CEV in primary cell populations and studying its functional associations in human cohorts. Analyses of 840 CEV phenotypes spanning multiple baseline measurements of 14 proteins in 28 T cell subpopulations suggest that the quantitative extent of CEV can exhibit substantial subject-to-subject differences and yet remain stable within healthy individuals over months. We linked CEV to age and disease-associated genetic polymorphisms, thus implicating CEV as a biomarker of aging and disease susceptibility and suggesting that it might play an important role in health and disease. Our dataset, interactive figures, and software for computing CEV with flow cytometry data provide a resource for exploring CEV functions.
authors.affiliation: Systems Genomics and Bioinformatics Unit, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation, NIH, Bethesda, MD 20892, USA.
authors.forename: Angelique
authors.initials: A
authors.lastname: Biancotto
authors.affiliation: Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation, NIH, Bethesda, MD 20892, USA.
authors.forename: Foo
authors.initials: F
authors.lastname: Cheung
authors.affiliation: National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: Remmers
authors.affiliation: Systems Genomics and Bioinformatics Unit, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Naisha
authors.initials: N
authors.lastname: Shah
authors.affiliation: Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation, NIH, Bethesda, MD 20892, USA; Hematology Branch, National Heart, Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: J Philip
authors.initials: JP
authors.lastname: McCoy
authors.affiliation: Systems Genomics and Bioinformatics Unit, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA; Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation, NIH, Bethesda, MD 20892, USA. Electronic address: john.tsang@nih.gov.
authors.forename: John S
authors.initials: JS
authors.lastname: Tsang
mesh_terms: D000375:Aging / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D013601:T-Lymphocytes / Q000276:immunology*