CONICET | Buscador de Institutos y Recursos Humanos

APRANK (Antigenic Peptide/Protein Ranker) a bioinformatic tool for genome-wide prioritization of candidate antigens of human pathogens Availability of validated antigens and B-cell epitopes is essential in the development of vaccines and diagnostics tests or to improve the performance of existing reagents. This knowledge is particularly important to take advantage of highly parallelized screening platforms, such as peptide or protein microarrays. By prioritizing candidate antigens, space in microarrays can be optimized to include the most relevant proteins from different co-endemic pathogens to screen for specific and cross-reactive antigens.With the recent availability of complete genomes of different pathogens, we are in a situation where computational strategies may now be attempted to prioritize potential new antigens at a genomic scale. We have developed an integrated bioinformatics pipeline (APRANK) that ranks the antigenicity of a protein by using a number of features predicted or measured from protein sequences to prioritize candidate antigens (and candidate antigenic peptides) from a given proteome. APRANK has been trained using a binomial logistic regression model with information on a number of known/validated antigens (positive examples) as well as negative/unknown examples.To validate APRANK, we measured its performance by training specific models for fifteen different species, dividing their data in training and test set multiple times and calculating the AUC of the predictions. We also created a single generic model made from the balanced data of all the fifteen species, and tested it against all species used for training as well as one novel species. Figure 1 shows the enrichment achieved by using our method on T. cruzi.Using a ROC curve analysis we demonstrate the predictive power of APRANK to prioritize antigens in several complete pathogen genomes and discuss the limitations of the approach. The main use of APRANK is to guide experimental work, helping in the design of peptide or protein microarrays or other methodologies, by effectively limiting the screening space to a reduced, more manageable set of candidates. Figure 1. Enrichment achieved by APRANK on T. cruzi. Increase in antigens obtained by using information of the whole proteins, peptides, or both (combined score). The combined score adds protein-level information to peptides, and is the mean of the other two scores.

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