title: Global analyses of human immune variation reveal baseline predictors of postvaccination responses.
abstract: A major goal of systems biology is the development of models that accurately predict responses to perturbation. Constructing such models requires the collection of dense measurements of system states, yet transformation of data into predictive constructs remains a challenge. To begin to model human immunity, we analyzed immune parameters in depth both at baseline and in response to influenza vaccination. Peripheral blood mononuclear cell transcriptomes, serum titers, cell subpopulation frequencies, and B cell responses were assessed in 63 individuals before and after vaccination and were used to develop a systematic framework to dissect inter- and intra-individual variation and build predictive models of postvaccination antibody responses. Strikingly, independent of age and pre-existing antibody titers, accurate models could be constructed using pre-perturbation cell populations alone, which were validated using independent baseline time points. Most of the parameters contributing to prediction delineated temporally stable baseline differences across individuals, raising the prospect of immune monitoring before intervention.
authors.affiliation: Trans-NIH Center for Human Immunology, Autoimmunity and Inflammation, National Institutes of Health, Bethesda, MD 20892, USA; Systems Genomics and Bioinformatics Unit, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: john.tsang@nih.gov.
authors.forename: John S
authors.initials: JS
authors.lastname: Tsang
authors.affiliation: Trans-NIH Center for Human Immunology, Autoimmunity and Inflammation, National Institutes of Health, Bethesda, MD 20892, USA; Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: pams@nhgri.nih.gov.
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Schwartzberg
authors.affiliation: Trans-NIH Center for Human Immunology, Autoimmunity and Inflammation, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Kotliarov
authors.affiliation: Trans-NIH Center for Human Immunology, Autoimmunity and Inflammation, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Angelique
authors.initials: A
authors.lastname: Biancotto
authors.affiliation: Trans-NIH Center for Human Immunology, Autoimmunity and Inflammation, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Trans-NIH Center for Human Immunology, Autoimmunity and Inflammation, National Institutes of Health, Bethesda, MD 20892, USA; Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Germain
authors.affiliation: Trans-NIH Center for Human Immunology, Autoimmunity and Inflammation, National Institutes of Health, Bethesda, MD 20892, USA; Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Ena
authors.initials: E
authors.lastname: Wang
authors.affiliation: Trans-NIH Center for Human Immunology, Autoimmunity and Inflammation, National Institutes of Health, Bethesda, MD 20892, USA; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Olnes
authors.affiliation: Systems Genomics and Bioinformatics Unit, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Manikandan
authors.initials: M
authors.lastname: Narayanan
authors.affiliation: Laboratory of Retrovirus Research, US Food and Drug Administration, Bethesda, MD 20892, USA.
authors.forename: Hana
authors.initials: H
authors.lastname: Golding
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Moir
authors.affiliation: Trans-NIH Center for Human Immunology, Autoimmunity and Inflammation, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Howard B
authors.initials: HB
authors.lastname: Dickler
authors.affiliation: Trans-NIH Center for Human Immunology, Autoimmunity and Inflammation, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Shira
authors.initials: S
authors.lastname: Perl
authors.affiliation: Trans-NIH Center for Human Immunology, Autoimmunity and Inflammation, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Foo
authors.initials: F
authors.lastname: Cheung
mesh_terms: D000328:Adult; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D059467:Transcriptome; D055815:Young Adult
chemical_list: D007252:Influenza Vaccines
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