GPS-MBA: computational analysis of MHC class II epitopes in type 1 diabetes

PLoS One. 2012;7(3):e33884. doi: 10.1371/journal.pone.0033884. Epub 2012 Mar 27.

Abstract

As a severe chronic metabolic disease and autoimmune disorder, type 1 diabetes (T1D) affects millions of people world-wide. Recent advances in antigen-based immunotherapy have provided a great opportunity for further treating T1D with a high degree of selectivity. It is reported that MHC class II I-A(g7) in the non-obese diabetic (NOD) mouse and human HLA-DQ8 are strongly linked to susceptibility to T1D. Thus, the identification of new I-A(g7) and HLA-DQ8 epitopes would be of great help to further experimental and biomedical manipulation efforts. In this study, a novel GPS-MBA (MHC Binding Analyzer) software package was developed for the prediction of I-A(g7) and HLA-DQ8 epitopes. Using experimentally identified epitopes as the training data sets, a previously developed GPS (Group-based Prediction System) algorithm was adopted and improved. By extensive evaluation and comparison, the GPS-MBA performance was found to be much better than other tools of this type. With this powerful tool, we predicted a number of potentially new I-A(g7) and HLA-DQ8 epitopes. Furthermore, we designed a T1D epitope database (TEDB) for all of the experimentally identified and predicted T1D-associated epitopes. Taken together, this computational prediction result and analysis provides a starting point for further experimental considerations, and GPS-MBA is demonstrated to be a useful tool for generating starting information for experimentalists. The GPS-MBA is freely accessible for academic researchers at: http://mba.biocuckoo.org.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Computational Biology / methods*
  • Databases, Protein
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / metabolism
  • Epitope Mapping
  • Epitopes* / chemistry
  • Epitopes* / metabolism
  • HLA-DQ Antigens / chemistry
  • HLA-DQ Antigens / immunology*
  • HLA-DQ Antigens / metabolism
  • Histocompatibility Antigens Class II / chemistry
  • Histocompatibility Antigens Class II / immunology*
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Internet
  • Mice
  • Peptides / chemistry
  • Peptides / metabolism
  • Protein Binding
  • Reproducibility of Results
  • Search Engine
  • Software*

Substances

  • Epitopes
  • HLA-DQ Antigens
  • HLA-DQ8 antigen
  • Histocompatibility Antigens Class II
  • I-A g7 antigen
  • Peptides