However, a growing number of reports associate certain DP and DQ alleles with several diseases, such as type I diabetes and coeliac disease,1–3 as well as in cancer.4–6 selleck products This gap in knowledge between DR and the other class II molecules has only recently begun to be filled, with the publication of larger sets of binding data for HLA DP and DQ molecules. In particular, a recent study by Wang et al.7 describes the release of an unprecedentedly large set of measured MHC class II binding affinities covering 26 allelic variants,
including a total of about 17 000 affinity measurements for five DP and six DQ molecules. The same study also compared the predictive performance of some of the best available bioinformatics methods on these data, and found that it was possible to obtain reliable binding predictions for DP and DQ at levels comparable to those for DR molecules. The same group, in two additional publications8,9 attempted to characterize the binding specificities of a number of DP and DQ ZD1839 price molecules using a matrix method called ARB (average relative binding).10 However,
this method has been shown to perform significantly worse than other comparable approaches for MHC class II binding prediction, such as the NN-align method.11 In this report, we applied the latest version of the NN-align algorithm, implemented as the NNAlign web-server,12 to exploit the newly available
large data sets of peptide from binding affinity to DP and DQ molecules and finely characterize the binding specificities of 11 DP and DQ molecules. NNAlign is a neural network-based method specifically designed to identify short linear motifs contained in large peptide data sets. As a direct result of the method, it identifies a core of consecutive amino acids within the peptide sequences that constitutes an informative motif. The method has been shown to perform significantly better than any other publicly available method for MHC class II binding prediction, including HLA-DP and HLA-DQ molecules.7 One of the strengths of this approach is the use of multiple neural networks, trained with different architectures and initial conditions, to reduce stochastic factors and at the same time combine information from the different networks in the ensemble to obtain a prediction that is better than what can be obtained from the individual networks. Although this ensemble approach has earlier proved to be highly effective in terms of improving the accuracy for binding affinity predictions,11 it has been demonstrated that the use of network ensembles could lead to a loss in accuracy when it comes to identification of the motif binding core.