Optimizing amino acid substitution matrices with a local alignment kernel

Hiroto Saigo, Jean Philippe Vert, Tatsuya Akutsu

研究成果: Contribution to journalArticle査読

31 被引用数 (Scopus)

抄録

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. Conclusion: 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.

本文言語英語
論文番号246
ジャーナルBMC bioinformatics
7
DOI
出版ステータス出版済み - 5 5 2006
外部発表はい

All Science Journal Classification (ASJC) codes

  • 構造生物学
  • 生化学
  • 分子生物学
  • コンピュータ サイエンスの応用
  • 応用数学

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