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Related Experiment Videos

Protein database searches using compositionally adjusted substitution matrices.

Stephen F Altschul1, John C Wootton, E Michael Gertz

  • 1National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. altschul@ncbi.nlm.nih.gov

The FEBS Journal
|October 13, 2005
PubMed
Summary
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Adjusting amino acid substitution matrices improves protein sequence alignment, especially for biased compositions. This method enhances database search accuracy and is now integrated into NCBI BLAST.

Area of Science:

  • Bioinformatics
  • Computational Biology
  • Molecular Biology

Background:

  • Protein sequence alignment relies heavily on amino acid substitution matrices.
  • Standard matrices perform suboptimally when comparing sequences with biased amino acid compositions.
  • Accurate scoring and statistical significance assessment are crucial for database search quality.

Purpose of the Study:

  • To present a method for adjusting standard substitution matrices for sequences with biased amino acid compositions.
  • To evaluate the effectiveness of these adjusted matrices in improving protein sequence alignments and scores.
  • To explore the applicability of compositional adjustment in general-purpose protein sequence database searches.

Main Methods:

  • Developed a general procedure to transform standard substitution matrices into compositionally adjusted ones.

Related Experiment Videos

  • Applied adjusted matrices to compare protein sequences with varying and biased amino acid compositions.
  • Assessed alignment quality and scores using adjusted versus standard matrices.

    • Main Results:

    • Compositionally adjusted matrices yield improved alignments and scores for proteins with marked compositional biases.
    • The study outlines criteria for beneficial application of compositional adjustment in general database searches.
    • Over half of related sequence pairs in typical database searches satisfy criteria for beneficial adjustment.

    Conclusions:

    • Compositional adjustment of amino acid substitution matrices enhances protein sequence comparison, particularly for biased compositions.
    • This method offers benefits for general database searches under specific criteria.
    • Compositional substitution matrix adjustment is now implemented in NCBI's protein-protein BLAST.