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

Li Liang, Xiaolin Tan, Silvia Juarez, Homarh Villaverde, Jozelyn Pablo, Rie Nakajima-Sasaki, Eduardo Gotuzzo, Mayuko Saito, Gary Hermanson, Douglas Molina, Scott Felgner, W. John W. Morrow, Xiaowu Liang, Robert H. Gilman, D. Huw Davies, Renée M. Tsolis, Joseph M. Vinetz, Philip L. Felgner

研究成果: Article査読

32 被引用数 (Scopus)


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.

ジャーナルJournal of Proteome Research
出版ステータスPublished - 2011 10 7

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

フィンガープリント 「Systems biology approach predicts antibody signature associated with Brucella melitensis infection in humans」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。