Global analyses of human immune variation reveal baseline predictors of postvaccination responses

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...

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Bibliographic Details
Published in:Cell 2014-04, Vol.157 (2), p.499-513
Main Authors: Tsang, John S, Schwartzberg, Pamela L, Kotliarov, Yuri, Biancotto, Angelique, Xie, Zhi, Germain, Ronald N, Wang, Ena, Olnes, Matthew J, Narayanan, Manikandan, Golding, Hana, Moir, Susan, Dickler, Howard B, Perl, Shira, Cheung, Foo
Format: Article
Language:English
Subjects:
Adult
antibodies
Antibody Formation
B-Lymphocytes - immunology
B-Lymphocytes - metabolism
blood serum
Female
Humans
immunity
influenza
Influenza Vaccines - administration & dosage
Influenza Vaccines - immunology
Leukocytes, Mononuclear - immunology
Leukocytes, Mononuclear - metabolism
Male
Middle Aged
monitoring
mononuclear leukocytes
prediction
Transcriptome
vaccination
Young Adult
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Summary: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.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2014.03.031