Predicting Class II MHC-Peptide binding: a kernel based approach using similarity scores

<p>Abstract</p> <p>Background</p> <p>Modelling the interaction between potentially antigenic peptides and Major Histocompatibility Complex (MHC) molecules is a key step in identifying potential T-cell epitopes. For Class II MHC alleles, the binding groove is open at bot...

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Main Authors: Flower Darren R, Salomon Jesper
Format: Article
Language:English
Published: BMC 2006-11-01
Series:BMC Bioinformatics
Online Access:http://www.biomedcentral.com/1471-2105/7/501
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author Flower Darren R
Salomon Jesper
author_facet Flower Darren R
Salomon Jesper
author_sort Flower Darren R
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Modelling the interaction between potentially antigenic peptides and Major Histocompatibility Complex (MHC) molecules is a key step in identifying potential T-cell epitopes. For Class II MHC alleles, the binding groove is open at both ends, causing ambiguity in the positional alignment between the groove and peptide, as well as creating uncertainty as to what parts of the peptide interact with the MHC. Moreover, the antigenic peptides have variable lengths, making naive modelling methods difficult to apply. This paper introduces a kernel method that can handle variable length peptides effectively by quantifying similarities between peptide sequences and integrating these into the kernel.</p> <p>Results</p> <p>The kernel approach presented here shows increased prediction accuracy with a significantly higher number of true positives and negatives on multiple MHC class II alleles, when testing data sets from MHCPEP <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>, MCHBN <abbrgrp><abbr bid="B2">2</abbr></abbrgrp>, and MHCBench <abbrgrp><abbr bid="B3">3</abbr></abbrgrp>. Evaluation by cross validation, when segregating binders and non-binders, produced an average of 0.824 A<sub>ROC </sub>for the MHCBench data sets (up from 0.756), and an average of 0.96 A<sub>ROC </sub>for multiple alleles of the MHCPEP database.</p> <p>Conclusion</p> <p>The method improves performance over existing state-of-the-art methods of MHC class II peptide binding predictions by using a custom, knowledge-based representation of peptides. Similarity scores, in contrast to a fixed-length, pocket-specific representation of amino acids, provide a flexible and powerful way of modelling MHC binding, and can easily be applied to other dynamic sequence problems.</p>
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spelling doaj.art-f5d41f76f6464f8ea57bacf751700cf12022-12-22T02:50:38ZengBMCBMC Bioinformatics1471-21052006-11-017150110.1186/1471-2105-7-501Predicting Class II MHC-Peptide binding: a kernel based approach using similarity scoresFlower Darren RSalomon Jesper<p>Abstract</p> <p>Background</p> <p>Modelling the interaction between potentially antigenic peptides and Major Histocompatibility Complex (MHC) molecules is a key step in identifying potential T-cell epitopes. For Class II MHC alleles, the binding groove is open at both ends, causing ambiguity in the positional alignment between the groove and peptide, as well as creating uncertainty as to what parts of the peptide interact with the MHC. Moreover, the antigenic peptides have variable lengths, making naive modelling methods difficult to apply. This paper introduces a kernel method that can handle variable length peptides effectively by quantifying similarities between peptide sequences and integrating these into the kernel.</p> <p>Results</p> <p>The kernel approach presented here shows increased prediction accuracy with a significantly higher number of true positives and negatives on multiple MHC class II alleles, when testing data sets from MHCPEP <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>, MCHBN <abbrgrp><abbr bid="B2">2</abbr></abbrgrp>, and MHCBench <abbrgrp><abbr bid="B3">3</abbr></abbrgrp>. Evaluation by cross validation, when segregating binders and non-binders, produced an average of 0.824 A<sub>ROC </sub>for the MHCBench data sets (up from 0.756), and an average of 0.96 A<sub>ROC </sub>for multiple alleles of the MHCPEP database.</p> <p>Conclusion</p> <p>The method improves performance over existing state-of-the-art methods of MHC class II peptide binding predictions by using a custom, knowledge-based representation of peptides. Similarity scores, in contrast to a fixed-length, pocket-specific representation of amino acids, provide a flexible and powerful way of modelling MHC binding, and can easily be applied to other dynamic sequence problems.</p>http://www.biomedcentral.com/1471-2105/7/501
spellingShingle Flower Darren R
Salomon Jesper
Predicting Class II MHC-Peptide binding: a kernel based approach using similarity scores
BMC Bioinformatics
title Predicting Class II MHC-Peptide binding: a kernel based approach using similarity scores
title_full Predicting Class II MHC-Peptide binding: a kernel based approach using similarity scores
title_fullStr Predicting Class II MHC-Peptide binding: a kernel based approach using similarity scores
title_full_unstemmed Predicting Class II MHC-Peptide binding: a kernel based approach using similarity scores
title_short Predicting Class II MHC-Peptide binding: a kernel based approach using similarity scores
title_sort predicting class ii mhc peptide binding a kernel based approach using similarity scores
url http://www.biomedcentral.com/1471-2105/7/501
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AT salomonjesper predictingclassiimhcpeptidebindingakernelbasedapproachusingsimilarityscores