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Iterated sequence databank search methods.

W R Taylor1, N P Brown

  • 1Division of Mathematical Biology, National Institute for Medical Research, Mill Hill, London, UK. w_taylor@nimr.mrc.ac.uk

Computers & Chemistry
|July 15, 1999
PubMed
Summary
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Comparing protein sequence search methods, QUEST and psi-BLAST effectively identified distant gene relatives in the Protein Data Bank (PDB). psi-BLAST excelled on larger datasets, while regular-expression matching proved limited for novel gene discovery.

Area of Science:

  • Bioinformatics
  • Computational Biology
  • Genomics

Background:

  • Identifying distant protein relatives is crucial for understanding novel gene functions.
  • Sequence databank searches are essential tools for evolutionary and structural biology.

Purpose of the Study:

  • To assess iterated sequence databank search methods for novel gene product analysis.
  • To compare the efficacy of pattern-matching, weighted profiles, and advanced algorithms in finding distant protein relatives and structures.

Main Methods:

  • Evaluated three search methods: regular-expression matching, QUEST (weighted matching), and psi-BLAST.
  • Focused investigation on the globin protein family for detailed analysis across different datasets and parameters.
  • Searched against both the Protein Data Bank (PDB) for known structures and larger sequence collections.

Related Experiment Videos

Main Results:

  • Regular-expression matching showed limited success, often restricted to closely related sub-families.
  • QUEST performed well on PDB, identifying most globins with few false positives, but struggled with full globin family alignment in larger datasets.
  • psi-BLAST recognized nearly all globins in PDB and performed robustly on larger databanks, with a similar false-positive rate to QUEST.
  • SAM showed variable performance, excelling only with comprehensive probe sets on larger databanks, and failing with Dirichlet mixtures.

Conclusions:

  • psi-BLAST and QUEST are effective for identifying distant protein relatives, especially within structured databases like PDB.
  • psi-BLAST demonstrates superior performance on large, diverse sequence datasets compared to QUEST and SAM.
  • The choice of search method and probe strategy significantly impacts the success of discovering homologous proteins and their structures.