title: 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 (R(p)). Our results show that every peptide position (P1-P9) contributes to TAP binding (minimum R(p) 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 (R(p) = 0.68 +/- 0.06) and the P1 (R(p) = 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 (R(p) = 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/.
authors.affiliation: Laboratorio de Inmuno Medicina, Departamento de Microbiología I-Immunología, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Diez-Rivero
authors.forename: Bernardo
authors.initials: B
authors.lastname: Chenlo
authors.forename: Pilar
authors.initials: P
authors.lastname: Zuluaga
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Reche
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000595:Amino Acid Sequence; D001185:Artificial Intelligence; D030562:Databases, Protein; D008954:Models, Biological; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport
chemical_list: D018528:ATP-Binding Cassette Transporters; D010455:Peptides; C477327:transporter associated with antigen processing (TAP)