Quantitative modeling of peptide binding to TAP using support vector machine

Abstract

The transport of peptides to the endoplasmic reticulum by the transporter associated with antigen processing (TAP) is a necessary step towards determining CD8 T cell epitopes. In this work, we have studied the predictive performance of support vector machine models trained on single residue positions and residue combinations drawn from a large dataset consisting of 613 nonamer peptides of known affinity to TAP. Predictive performance of these TAP affinity models was evaluated under 10‐fold cross‐validation experiments and measured using Pearson's correlation coefficients (Rp). Our results show that every peptide position (P1–P9) contributes to TAP binding (minimum Rp of 0.26 ± 0.11 was achieved by a model trained on the P6 residue), although the largest contributions to binding correspond to the C‐terminal end (Rp = 0.68 ± 0.06) and the P1 (Rp = 0.51 ± 0.09) and P2 (0.57 ± 0.08) residues of the peptide. Training the models on additional peptide residues generally improved their predictive performance and a maximum correlation (Rp = 0.89 ± 0.03) was achieved by a model trained on the full‐length sequences or a residue selection consisting of the first 5 N‐ and last 3 C‐terminal residues of the peptides included in the training set. A system for predicting the binding affinity of peptides to TAP using the methods described here is readily available for free public use at http://imed.med.ucm.es/Tools/tapreg/. Proteins 2010. © 2009 Wiley‐Liss, Inc.

Peptide Handling by HLA-B27 Subtypes Influences Their Biological Behavior, Association with Ankylosing Spondylitis and Susceptibility to Endoplasmic Reticulum Aminopeptidase 1 (ERAP1)

“…TAP-binding Affinity-This was estimated for HLA-B27 ligands and their N-terminally extended precursors using the TAPREG tool (43), which makes use of support vector machines trained with large peptide sets to predict the TAP binding affinity of peptides of eight to 16 residues. Statistical significance between peptide sets was assessed with the Mann-Whitney test.…”

“…The affinity of peptides for TAP depends on their whole sequence (43), but mainly on the three N-terminal and the C-terminal residues (51). The TAP-binding affinity of HLA-B27 ligands and their N-terminally extended precursors, by 1 to 4 residues, was compared using a predictive algorithm that takes into account the contribution of all peptide resi- dues (43).…”

“…The TAP-binding affinity of HLA-B27 ligands and their N-terminally extended precursors, by 1 to 4 residues, was compared using a predictive algorithm that takes into account the contribution of all peptide resi- dues (43). The final HLA-B27 ligands were significantly more suited to TAP than any of their N-terminally extended precursors.…”

“…Bars indicate the geometrical mean values of each peptide set. Affinity was calculated as previously described (43). The significance of the differences among peptide sets was assessed by the Mann-Whitney test.…”

Expression Library Immunization Can Confer Protection against Lethal Challenge with African Swine Fever Virus

“…Fibroblasts isolated from ASFV Ublib -vaccinated and surviving pigs will be transfected with individual ASFV Ublib plasmids and then used as APCs. Once identified, the corresponding ASFV polypeptides will be subjected to a detailed in silico prediction of CTL epitopes (59). This two-step method coupled with the abovementioned readouts has allowed the identification of a few protective CTL determinants in vitro (18).…”