A comparison of scoring functions for protein sequence profile alignment

Bioinformatics. 2004 May 22;20(8):1301-8. doi: 10.1093/bioinformatics/bth090. Epub 2004 Feb 12.


Motivation: In recent years, several methods have been proposed for aligning two protein sequence profiles, with reported improvements in alignment accuracy and homolog discrimination versus sequence-sequence methods (e.g. BLAST) and profile-sequence methods (e.g. PSI-BLAST). Profile-profile alignment is also the iterated step in progressive multiple sequence alignment algorithms such as CLUSTALW. However, little is known about the relative performance of different profile-profile scoring functions. In this work, we evaluate the alignment accuracy of 23 different profile-profile scoring functions by comparing alignments of 488 pairs of sequences with identity < or =30% against structural alignments. We optimize parameters for all scoring functions on the same training set and use profiles of alignments from both PSI-BLAST and SAM-T99. Structural alignments are constructed from a consensus between the FSSP database and CE structural aligner. We compare the results with sequence-sequence and sequence-profile methods, including BLAST and PSI-BLAST.

Results: We find that profile-profile alignment gives an average improvement over our test set of typically 2-3% over profile-sequence alignment and approximately 40% over sequence-sequence alignment. No statistically significant difference is seen in the relative performance of most of the scoring functions tested. Significantly better results are obtained with profiles constructed from SAM-T99 alignments than from PSI-BLAST alignments.

Availability: Source code, reference alignments and more detailed results are freely available at http://phylogenomics.berkeley.edu/profilealignment/

Publication types

  • Comparative Study
  • Evaluation Study
  • Validation Study

MeSH terms

  • Algorithms*
  • Amino Acid Sequence
  • Gene Expression Profiling / methods*
  • Molecular Sequence Data
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Sequence Alignment / methods*
  • Sequence Analysis, Protein / methods*
  • Sequence Homology, Amino Acid