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Systems Biology Approach Predicts Antibody Signature Associated with Brucella melitensis Infection in Humans
[Image: see text] 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 melitens...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189706/ https://www.ncbi.nlm.nih.gov/pubmed/21863892 http://dx.doi.org/10.1021/pr200619r |
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author | Liang, Li Tan, Xiaolin Juarez, Silvia Villaverde, Homarh Pablo, Jozelyn Nakajima-Sasaki, Rie Gotuzzo, Eduardo Saito, Mayuko Hermanson, Gary Molina, Douglas Felgner, Scott Morrow, W. John W. Liang, Xiaowu Gilman, Robert H. Davies, D. Huw Tsolis, Renée M. Vinetz, Joseph M. Felgner, Philip L. |
author_facet | Liang, Li Tan, Xiaolin Juarez, Silvia Villaverde, Homarh Pablo, Jozelyn Nakajima-Sasaki, Rie Gotuzzo, Eduardo Saito, Mayuko Hermanson, Gary Molina, Douglas Felgner, Scott Morrow, W. John W. Liang, Xiaowu Gilman, Robert H. Davies, D. Huw Tsolis, Renée M. Vinetz, Joseph M. Felgner, Philip L. |
author_sort | Liang, Li |
collection | PubMed |
description | [Image: see text] 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. |
format | Online Article Text |
id | pubmed-3189706 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-31897062011-10-11 Systems Biology Approach Predicts Antibody Signature Associated with Brucella melitensis Infection in Humans Liang, Li Tan, Xiaolin Juarez, Silvia Villaverde, Homarh Pablo, Jozelyn Nakajima-Sasaki, Rie Gotuzzo, Eduardo Saito, Mayuko Hermanson, Gary Molina, Douglas Felgner, Scott Morrow, W. John W. Liang, Xiaowu Gilman, Robert H. Davies, D. Huw Tsolis, Renée M. Vinetz, Joseph M. Felgner, Philip L. J Proteome Res [Image: see text] 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. American Chemical Society 2011-08-24 2011-10-07 /pmc/articles/PMC3189706/ /pubmed/21863892 http://dx.doi.org/10.1021/pr200619r Text en Copyright © 2011 American Chemical Society http://pubs.acs.orgThis is an open-access article distributed under the ACS AuthorChoice Terms & Conditions. Any use of this article, must conform to the terms of that license which are available at http://pubs.acs.org. |
spellingShingle | Liang, Li Tan, Xiaolin Juarez, Silvia Villaverde, Homarh Pablo, Jozelyn Nakajima-Sasaki, Rie Gotuzzo, Eduardo Saito, Mayuko Hermanson, Gary Molina, Douglas Felgner, Scott Morrow, W. John W. Liang, Xiaowu Gilman, Robert H. Davies, D. Huw Tsolis, Renée M. Vinetz, Joseph M. Felgner, Philip L. Systems Biology Approach Predicts Antibody Signature Associated with Brucella melitensis Infection in Humans |
title | Systems Biology Approach Predicts Antibody Signature Associated with Brucella melitensis Infection in Humans |
title_full | Systems Biology Approach Predicts Antibody Signature Associated with Brucella melitensis Infection in Humans |
title_fullStr | Systems Biology Approach Predicts Antibody Signature Associated with Brucella melitensis Infection in Humans |
title_full_unstemmed | Systems Biology Approach Predicts Antibody Signature Associated with Brucella melitensis Infection in Humans |
title_short | Systems Biology Approach Predicts Antibody Signature Associated with Brucella melitensis Infection in Humans |
title_sort | systems biology approach predicts antibody signature associated with brucella melitensis infection in humans |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189706/ https://www.ncbi.nlm.nih.gov/pubmed/21863892 http://dx.doi.org/10.1021/pr200619r |
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