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Related Experiment Videos

Combining sensitive database searches with multiple intermediates to detect distant homologues.

A A Salamov1, M Suwa, C A Orengo

  • 1Helix Research Institute, Chiba, Japan.

Protein Engineering
|April 9, 1999
PubMed
Summary
This summary is machine-generated.

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This study evaluated sequence searching algorithms, finding that multiple intermediate sequence search (MISS) significantly improves relationship detection over standard methods like BLAST. MISS enhances sensitivity by leveraging sequence diversity for broader applicability.

Area of Science:

  • Bioinformatics
  • Computational Biology
  • Structural Bioinformatics

Background:

  • Accurate identification of homologous protein sequences is crucial for understanding protein function and evolution.
  • Existing sequence search algorithms have limitations in sensitivity and scope, particularly for distantly related proteins.
  • The CATH structure classification database provides a framework for assessing protein relationships.

Purpose of the Study:

  • To assess the performance of common sequence search algorithms (blastp, fasta, smith-waterman, gapped-blast).
  • To develop and evaluate a novel method, Multiple Intermediate Sequence Search (MISS), for enhancing remote homology detection.
  • To establish safe thresholds for database searching and normalization schemes.

Main Methods:

Related Experiment Videos

  • Comparative analysis of blastp, fasta, smith-waterman, and gapped-blast algorithms using CATH data.
  • Implementation and testing of an intermediate sequence search strategy.
  • Development and validation of the Multiple Intermediate Sequence Search (MISS) procedure on a large dataset of homologous families.

    • Main Results:

    • fasta, smith-waterman, and gapped-blast showed similar performance, outperforming blastp in sensitivity.
    • Intermediate sequence searches significantly improved the detection of relationships missed by blastp, doubling the discovery rate compared to smith-waterman alone in some cases.
    • The MISS procedure identified 241 additional relationships across 1906 cases that were undetectable by previous methods, demonstrating its enhanced sensitivity.

    Conclusions:

    • The MISS procedure offers a significant improvement in detecting remote protein sequence relationships by utilizing sequence diversity.
    • MISS is more generally applicable than structure-dependent methods like fold recognition and threading.
    • The effectiveness of intermediate searches is influenced by the number and diversity of available sequences within protein families.