Iterative stepwise discriminant analysis: a meta-algorithm for detecting quantitative sequence motifs.

An algorithm is presented for detecting a quantitative pattern in peptide fragments that bind class II major histocompatibility complex (MHC) molecules. It is referred to as a meta-algorithm because it requires successive applications of Stepwise Discriminate Analysis (SDA). On every iteration the best subsequence candidates are selected from sequences known to bind class II MHC molecules. When SDA compares probable binding subsequences with subsequences known not to bind class II MHC molecules, a quantitative model emerges that is capable of classifying subsequences as binding or non-binding. In an iterative manner, the resultant model is utilized as a criterion for selecting probable binding subsequence candidates. The procedure is repeated until models converge. In the illustrated examples, the final models correctly classify over 95% of the peptides in a database of peptides whose binding affinity for HLA-DR1 is known. The final model can then be used to predict the binding affinity of peptides that have not yet been laboratory tested.