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Related Experiment Videos

Using evolutionary information for the query and target improves fold recognition.

Björn Wallner1, Huisheng Fang, Tomas Ohlson

  • 1Stockholm Bioinformatics Center, Stockholm University, Stockholm, Sweden.

Proteins
|December 30, 2003
PubMed
Summary
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Enhanced evolutionary information improves protein domain detection beyond PSI-BLAST. Combining sequence and profile searches offers the best balance of speed, accuracy, and low computational cost for identifying superfamily-related protein domains.

Area of Science:

  • Bioinformatics
  • Computational Biology
  • Structural Bioinformatics

Background:

  • Protein domain identification is crucial for understanding protein function and evolution.
  • PSI-BLAST is a standard tool, but its performance can be limited.
  • Leveraging evolutionary information can enhance sequence similarity searches.

Purpose of the Study:

  • To evaluate methods for improving protein domain detection performance over PSI-BLAST.
  • To investigate the utility of evolutionary information in sequence and profile-based searches.
  • To compare the accuracy, speed, and computational cost of different search strategies.

Main Methods:

  • Utilizing evolutionary information through sequence linking.
  • Employing profile-profile alignments for domain detection.

Related Experiment Videos

  • Combining sequence-profile and profile-sequence searches.
  • Assessing performance at 90% specificity for superfamily-related protein domains.

    • Main Results:

    • Sequence linking identified 22% of domains, profile-profile alignments 19%, and combined searches 20%, all outperforming PSI-BLAST's 16%.
    • Combined searches offer optimal speed and accuracy, especially at high specificity.
    • E-values reported by all methods, including PSI-BLAST, underestimate false positive rates, particularly with looser cutoffs and more iterations.

    Conclusions:

    • Integrating evolutionary information significantly enhances protein domain detection sensitivity.
    • Combined sequence-profile and profile-sequence searches provide a computationally efficient and accurate approach.
    • The underestimation of false positive rates necessitates careful interpretation of E-values in protein domain searches.