NN-align. An artificial neural network-based alignment algorithm for MHC class II peptide binding prediction

BMC Bioinformatics. 2009 Sep 18;10:296. doi: 10.1186/1471-2105-10-296.


Background: The major histocompatibility complex (MHC) molecule plays a central role in controlling the adaptive immune response to infections. MHC class I molecules present peptides derived from intracellular proteins to cytotoxic T cells, whereas MHC class II molecules stimulate cellular and humoral immunity through presentation of extracellularly derived peptides to helper T cells. Identification of which peptides will bind a given MHC molecule is thus of great importance for the understanding of host-pathogen interactions, and large efforts have been placed in developing algorithms capable of predicting this binding event.

Results: Here, we present a novel artificial neural network-based method, NN-align that allows for simultaneous identification of the MHC class II binding core and binding affinity. NN-align is trained using a novel training algorithm that allows for correction of bias in the training data due to redundant binding core representation. Incorporation of information about the residues flanking the peptide-binding core is shown to significantly improve the prediction accuracy. The method is evaluated on a large-scale benchmark consisting of six independent data sets covering 14 human MHC class II alleles, and is demonstrated to outperform other state-of-the-art MHC class II prediction methods.

Conclusion: The NN-align method is competitive with the state-of-the-art MHC class II peptide binding prediction algorithms. The method is publicly available at http://www.cbs.dtu.dk/services/NetMHCII-2.0.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Algorithms*
  • Binding Sites
  • Computational Biology / methods*
  • Databases, Protein
  • Histocompatibility Antigens Class II / chemistry*
  • Histocompatibility Antigens Class II / metabolism
  • Neural Networks, Computer*
  • Peptides / chemistry*
  • Peptides / metabolism*
  • Protein Binding
  • Protein Interaction Mapping / methods
  • Sequence Alignment / methods*
  • Sequence Analysis, Protein / methods


  • Histocompatibility Antigens Class II
  • Peptides