Protein sequence-similarity search acceleration using a heuristic algorithm with a sensitive matrix.

Journal: Journal of structural and functional genomics
Published Date:

Abstract

Protein database search for public databases is a fundamental step in the target selection of proteins in structural and functional genomics and also for inferring protein structure, function, and evolution. Most database search methods employ amino acid substitution matrices to score amino acid pairs. The choice of substitution matrix strongly affects homology detection performance. We earlier proposed a substitution matrix named MIQS that was optimized for distant protein homology search. Herein we further evaluate MIQS in combination with LAST, a heuristic and fast database search tool with a tunable sensitivity parameter m, where larger m denotes higher sensitivity. Results show that MIQS substantially improves the homology detection and alignment quality performance of LAST across diverse m parameters. Against a protein database consisting of approximately 15 million sequences, LAST with m = 10 achieves better homology detection performance than BLASTP, and completes the search 20 times faster. Compared to the most sensitive existing methods being used today, CS-BLAST and SSEARCH, LAST with MIQS and m = 10 shows comparable homology detection performance at 2.0 and 3.9 times greater speed, respectively. Results demonstrate that MIQS-powered LAST is a time-efficient method for sensitive and accurate homology search.

Authors

  • Kyungtaek Lim
    Artificial Intelligence Research Center, National Institute of Advanced Industrial Science and Technology (AIST), 2-4-7 Aomi, Koto-ku, Tokyo, 135-0064, Japan.
  • Kazunori D Yamada
    Artificial Intelligence Research Center, National Institute of Advanced Industrial Science and Technology (AIST), 2-4-7 Aomi, Koto-ku, Tokyo, 135-0064, Japan.
  • Martin C Frith
    Artificial Intelligence Research Center, National Institute of Advanced Industrial Science and Technology (AIST), 2-4-7 Aomi, Koto-ku, Tokyo, 135-0064, Japan.
  • Kentaro Tomii
    Artificial Intelligence Research Center, National Institute of Advanced Industrial Science and Technology (AIST), 2-4-7 Aomi, Koto-ku, Tokyo, 135-0064, Japan. k-tomii@aist.go.jp.