Homology-extended sequence alignment

Nucleic Acids Res. 2005 Feb 7;33(3):816-24. doi: 10.1093/nar/gki233. Print 2005.


We present a profile-profile multiple alignment strategy that uses database searching to collect homologues for each sequence in a given set, in order to enrich their available evolutionary information for the alignment. For each of the alignment sequences, the putative homologous sequences that score above a pre-defined threshold are incorporated into a position-specific pre-alignment profile. The enriched position-specific profile is used for standard progressive alignment, thereby more accurately describing the characteristic features of the given sequence set. We show that owing to the incorporation of the pre-alignment information into a standard progressive multiple alignment routine, the alignment quality between distant sequences increases significantly and outperforms state-of-the-art methods, such as T-COFFEE and MUSCLE. We also show that although entirely sequence-based, our novel strategy is better at aligning distant sequences when compared with a recent contact-based alignment method. Therefore, our pre-alignment profile strategy should be advantageous for applications that rely on high alignment accuracy such as local structure prediction, comparative modelling and threading.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Amino Acid Sequence
  • Molecular Sequence Data
  • Sequence Alignment / methods*
  • Sequence Analysis, Protein / methods*
  • Software