title: Gene signatures related to B-cell proliferation predict influenza vaccine-induced antibody response.
abstract: Vaccines are very effective at preventing infectious disease but not all recipients mount a protective immune response to vaccination. Recently, gene expression profiles of PBMC samples in vaccinated individuals have been used to predict the development of protective immunity. However, the magnitude of change in gene expression that separates vaccine responders and nonresponders is likely to be small and distributed across networks of genes, making the selection of predictive and biologically relevant genes difficult. Here we apply a new approach to predicting vaccine response based on coordinated upregulation of sets of biologically informative genes in postvaccination gene expression profiles. We found that enrichment of gene sets related to proliferation and immunoglobulin genes accurately segregated high responders to influenza vaccination from low responders and achieved a prediction accuracy of 88% in an independent clinical trial. Many of the genes in these gene sets would not have been identified using conventional, single-gene level approaches because of their subtle upregulation in vaccine responders. Our results demonstrate that gene set enrichment method can capture subtle transcriptional changes and may be a generally useful approach for developing and interpreting predictive models of the human immune response.
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA, USA; Bioinformatics Program, Boston University, Boston, MA, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Tan
authors.forename: Pablo
authors.initials: P
authors.lastname: Tamayo
authors.forename: Helder
authors.initials: H
authors.lastname: Nakaya
authors.forename: Bali
authors.initials: B
authors.lastname: Pulendran
authors.forename: Jill P
authors.initials: JP
authors.lastname: Mesirov
authors.forename: W Nicholas
authors.initials: WN
authors.lastname: Haining
mesh_terms: D000914:Antibodies, Viral / Q000276:immunology*; D000917:Antibody Formation / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology*; D048708:Cell Growth Processes / Q000235:genetics; D006801:Humans; D007252:Influenza Vaccines; D007251:Influenza, Human / Q000175:diagnosis* / Q000276:immunology; D046228:Microarray Analysis; D018448:Models, Immunological; D057089:Pathology, Molecular; D011237:Predictive Value of Tests; D011379:Prognosis; D059467:Transcriptome; D016896:Treatment Outcome; D014611:Vaccination
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines
keywords: B-Cell proliferation; Gene expression; Immune response; Systems biology; Vaccine efficacy