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High-throughput prediction of protein antigenicity using protein microarray data.


ABSTRACT:

Motivation

Discovery of novel protective antigens is fundamental to the development of vaccines for existing and emerging pathogens. Most computational methods for predicting protein antigenicity rely directly on homology with previously characterized protective antigens; however, homology-based methods will fail to discover truly novel protective antigens. Thus, there is a significant need for homology-free methods capable of screening entire proteomes for the antigens most likely to generate a protective humoral immune response.

Results

Here we begin by curating two types of positive data: (i) antigens that elicit a strong antibody response in protected individuals but not in unprotected individuals, using human immunoglobulin reactivity data obtained from protein microarray analyses; and (ii) known protective antigens from the literature. The resulting datasets are used to train a sequence-based prediction model, ANTIGENpro, to predict the likelihood that a protein is a protective antigen. ANTIGENpro correctly classifies 82% of the known protective antigens when trained using only the protein microarray datasets. The accuracy on the combined dataset is estimated at 76% by cross-validation experiments. Finally, ANTIGENpro performs well when evaluated on an external pathogen proteome for which protein microarray data were obtained after the initial development of ANTIGENpro.

Availability

ANTIGENpro is integrated in the SCRATCH suite of predictors available at http://scratch.proteomics.ics.uci.edu.

Contact

pfbaldi@ics.uci.edu

SUBMITTER: Magnan CN 

PROVIDER: S-EPMC2982151 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Publications

High-throughput prediction of protein antigenicity using protein microarray data.

Magnan Christophe N CN   Zeller Michael M   Kayala Matthew A MA   Vigil Adam A   Randall Arlo A   Felgner Philip L PL   Baldi Pierre P  

Bioinformatics (Oxford, England) 20101007 23


<h4>Motivation</h4>Discovery of novel protective antigens is fundamental to the development of vaccines for existing and emerging pathogens. Most computational methods for predicting protein antigenicity rely directly on homology with previously characterized protective antigens; however, homology-based methods will fail to discover truly novel protective antigens. Thus, there is a significant need for homology-free methods capable of screening entire proteomes for the antigens most likely to ge  ...[more]

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