Introduction to the Peptide Binding Problem of Computational Immunology: New Results
We attempt to establish geometrical methods for amino acid sequences. To measure the similarities of these sequences, a kernel on strings is defined using only the sequence structure and a good amino acid substitution matrix (e.g. BLOSUM62). The kernel is used in learning machines to predict binding affinities of peptides to human leukocyte antigen DR (HLA-DR) molecules. On both fixed allele (Nielsen and Lund in BMC Bioinform. 10:296, 2009) and pan-allele (Nielsen et al. in Immunome Res. 6(1):9, 2010) benchmark databases, our algorithm achieves the state-of-the-art performance. The kernel is also used to define a distance on an HLA-DR allele set based on which a clustering analysis precisely recovers the serotype classifications assigned by WHO (Holdsworth et al. in Tissue Antigens 73(2):95170, 2009; Marsh et al. in Tissue Antigens 75(4):291455, 2010). These results suggest that our kernel relates well the sequence structure of both peptides and HLA-DR molecules to their biological functions, and that it offers a simple, powerful and promising methodology to immunology and amino acid sequence studies.
string kernel peptide binding prediction reproducing kernel hilbert space major histocompatibility complex hla drb allele classification 62p10 68t05 92b15 92c40