Optimizing amino acid substitution matrices with a local alignment kernel.
BACKGROUND
Detecting remote homologies by direct comparison of protein sequences remains a challenging task. We had previously developed a similarity score between sequences, called a local alignment kernel, that exhibits good performance for this task in combination with a support vector machine. The local alignment kernel depends on an amino acid substitution matrix. Since commonly used BLOSUM or PAM matrices for scoring amino acid matches have been optimized to be used in combination with the Smith-Waterman algorithm, the matrices optimal for the local alignment kernel can be different.


RESULTS
Contrary to the local alignment score computed by the Smith-Waterman algorithm, the local alignment kernel is differentiable with respect to the amino acid substitution and its derivative can be computed efficiently by dynamic programming. We optimized the substitution matrix by classical gradient descent by setting an objective function that measures how well the local alignment kernel discriminates homologs from non-homologs in the COG database. The local alignment kernel exhibits better performance when it uses the matrices and gap parameters optimized by this procedure than when it uses the matrices optimized for the Smith-Waterman algorithm. Furthermore, the matrices and gap parameters optimized for the local alignment kernel can also be used successfully by the Smith-Waterman algorithm.


CONCLUSIONS
This optimization procedure leads to useful substitution matrices, both for the local alignment kernel and the Smith-Waterman algorithm. The best performance for homology detection is obtained by the local alignment kernel.
Saigo
Hiroto
H
Bioinformatics Center, Institute for Chemical Research, Kyoto University, Uji, 611-0011, Japan. hiroto@kuicr.kyoto-u.ac.jp
Vert
Jean-Philippe
JP
Akutsu
Tatsuya
T