Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2011
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
_version_ 1782213496089346048
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
work_keys_str_mv AT liangli systemsbiologyapproachpredictsantibodysignatureassociatedwithbrucellamelitensisinfectioninhumans
AT tanxiaolin systemsbiologyapproachpredictsantibodysignatureassociatedwithbrucellamelitensisinfectioninhumans
AT juarezsilvia systemsbiologyapproachpredictsantibodysignatureassociatedwithbrucellamelitensisinfectioninhumans
AT villaverdehomarh systemsbiologyapproachpredictsantibodysignatureassociatedwithbrucellamelitensisinfectioninhumans
AT pablojozelyn systemsbiologyapproachpredictsantibodysignatureassociatedwithbrucellamelitensisinfectioninhumans
AT nakajimasasakirie systemsbiologyapproachpredictsantibodysignatureassociatedwithbrucellamelitensisinfectioninhumans
AT gotuzzoeduardo systemsbiologyapproachpredictsantibodysignatureassociatedwithbrucellamelitensisinfectioninhumans
AT saitomayuko systemsbiologyapproachpredictsantibodysignatureassociatedwithbrucellamelitensisinfectioninhumans
AT hermansongary systemsbiologyapproachpredictsantibodysignatureassociatedwithbrucellamelitensisinfectioninhumans
AT molinadouglas systemsbiologyapproachpredictsantibodysignatureassociatedwithbrucellamelitensisinfectioninhumans
AT felgnerscott systemsbiologyapproachpredictsantibodysignatureassociatedwithbrucellamelitensisinfectioninhumans
AT morrowwjohnw systemsbiologyapproachpredictsantibodysignatureassociatedwithbrucellamelitensisinfectioninhumans
AT liangxiaowu systemsbiologyapproachpredictsantibodysignatureassociatedwithbrucellamelitensisinfectioninhumans
AT gilmanroberth systemsbiologyapproachpredictsantibodysignatureassociatedwithbrucellamelitensisinfectioninhumans
AT daviesdhuw systemsbiologyapproachpredictsantibodysignatureassociatedwithbrucellamelitensisinfectioninhumans
AT tsolisreneem systemsbiologyapproachpredictsantibodysignatureassociatedwithbrucellamelitensisinfectioninhumans
AT vinetzjosephm systemsbiologyapproachpredictsantibodysignatureassociatedwithbrucellamelitensisinfectioninhumans
AT felgnerphilipl systemsbiologyapproachpredictsantibodysignatureassociatedwithbrucellamelitensisinfectioninhumans