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Systems biology approach predicts antibody signature associated with Brucella melitensis infection in humans

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dc.contributor.author Liang, L.
dc.contributor.author Tan, X.
dc.contributor.author Juarez, S.
dc.contributor.author Villaverde, H.
dc.contributor.author Pablo, J.
dc.contributor.author Nakajima-Sasaki, R.
dc.contributor.author Gotuzzo Herencia, José Eduardo
dc.contributor.author Saito, M.
dc.contributor.author Hermanson, G.
dc.contributor.author Molina, D.
dc.contributor.author Felgner, S.
dc.contributor.author Morrow, W.J.W.
dc.contributor.author Liang, X.
dc.contributor.author Gilman, Robert Hugh
dc.contributor.author Davies, D.H.
dc.contributor.author Tsolis, R.M.
dc.contributor.author Vinetz, Joseph Michael
dc.contributor.author Felgner, P.L.
dc.date.accessioned 2022-01-18T19:26:49Z
dc.date.available 2022-01-18T19:26:49Z
dc.date.issued 2011
dc.identifier.uri https://hdl.handle.net/20.500.12866/10911
dc.description.abstract A complete understanding of the factors that determine selection of antigens recognized by the humoral immune response following infectious agent challenge is lacking. Here we illustrate a systems biology approach to identify the antibody signature associated with Brucella melitensis (Bm) infection in humans and predict proteomic features of serodiagnostic antigens. By taking advantage of a full proteome microarray expressing previously cloned 1406 and newly cloned 1640 Bm genes, we were able to identify 122 immunodominant antigens and 33 serodiagnostic antigens. The reactive antigens were then classified according to annotated functional features (COGs), computationally predicted features (e.g., subcellular localization, physical properties), and protein expression estimated by mass spectrometry (MS). Enrichment analyses indicated that membrane association and secretion were significant enriching features of the reactive antigens, as were proteins predicted to have a signal peptide, a single transmembrane domain, and outer membrane or periplasmic location. These features accounted for 67% of the serodiagnostic antigens. An overlay of the seroreactive antigen set with proteomic data sets generated by MS identified an additional 24%, suggesting that protein expression in bacteria is an additional determinant in the induction of Brucella-specific antibodies. This analysis indicates that one-third of the proteome contains enriching features that account for 91% of the antigens recognized, and after B. melitensis infection the immune system develops significant antibody titers against 10% of the proteins with these enriching features. This systems biology approach provides an empirical basis for understanding the breadth and specificity of the immune response to B. melitensis and a new framework for comparing the humoral responses against other microorganisms. en_US
dc.language.iso eng
dc.publisher American Chemical Society
dc.relation.ispartofseries Journal of Proteome Research
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Humans en_US
dc.subject Controlled Study en_US
dc.subject Major Clinical Study en_US
dc.subject Protein Expression en_US
dc.subject Nucleotide Sequence en_US
dc.subject Disease Association en_US
dc.subject Gene Expression Regulation en_US
dc.subject Reproducibility Of Results en_US
dc.subject Bacterial Proteins en_US
dc.subject Protein Secretion en_US
dc.subject Immunity en_US
dc.subject Bacterial Gene en_US
dc.subject Brucella Melitensis en_US
dc.subject Brucellosis en_US
dc.subject Bacteria (Microorganisms) en_US
dc.subject Immune Response en_US
dc.subject Mass Spectrometry en_US
dc.subject Proteome en_US
dc.subject Protein Analysis en_US
dc.subject Antibodies en_US
dc.subject Bacterial Antigen en_US
dc.subject Cellular Distribution en_US
dc.subject Protein Microarray en_US
dc.subject Lipopolysaccharides en_US
dc.subject Bacterium Antibody en_US
dc.subject Brucella en_US
dc.subject Cell Membrane en_US
dc.subject Clone en_US
dc.subject Enriching Features en_US
dc.subject Immune System en_US
dc.subject Open Reading Frames en_US
dc.subject Protein Array Analysis en_US
dc.subject Proteomics en_US
dc.subject Systems Biology en_US
dc.title Systems biology approach predicts antibody signature associated with Brucella melitensis infection in humans en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1021/pr200619r
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.01.00
dc.relation.issn 1535-3907


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