PRED(TAP): a system for prediction of peptide binding to the human transporter associated with antigen processing

Abstract

Background: The transporter associated with antigen processing (TAP) is a critical component of the major histocompatibility complex (MHC) class I antigen processing and presentation pathway. TAP transports antigenic peptides into the endoplasmic reticulum where it loads them into the binding groove of MHC class I molecules. Because peptides must first be transported by TAP in order to be presented on MHC class I, TAP binding preferences should impact significantly on T-cell epitope selection.

Description: PRED(TAP) is a computational system that predicts peptide binding to human TAP. It uses artificial neural networks and hidden Markov models as predictive engines. Extensive testing was performed to valid the prediction models. The results showed that PRED(TAP) was both sensitive and specific and had good predictive ability (area under the receiver operating characteristic curve Aroc>0.85).

Conclusion: PRED(TAP) can be integrated with prediction systems for MHC class I binding peptides for improved performance of in silico prediction of T-cell epitopes. PRED(TAP) is available for public use at [1].

Figure 1

Plot of sensitivity and specificity of ANN model against thresholds in 10-fold cross-validation. The ANN model for prediction of A) LMH set, B) MH set, and C) H set.

Figure 2

Plot of sensitivity and specificity of HMM model against thresholds in 10-fold cross-validation. The HMM model for prediction of A) LMH set, B) MH set, and C) H set.

Figure 3

The examples of the output pages of PRED^TAP for a single protein. The sequence type chosen is "protein sequence". A) The input page. B) The main result page. The input sequence is decomposed into overlapping 9-mers for prediction of binding scores to TAP. C) Alignment view of the predicted TAP binding regions in the input protein.

Figure 4

An example of the output pages of PRED^TAP for a list of peptides. A) The input page. B) The main result page. All 9-mers in each peptide were submitted for prediction. The predicted binding scores are represented by the highest individual 9-mer binding score of each input peptide. The 9-mer with the highest binding score in each peptide is displayed as "Binding Core" in the result table.