Homology-extended sequence alignment

Abstract

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.

Cite this paper

@article{simossis2005homology,
  title = {{Homology-extended sequence alignment}},
  author = {Simossis, V. A.},
  journal = {Nucleic Acids Research},
  volume = {33},
  number = {3},
  pages = {816--824},
  year = {2005},
  doi = {10.1093/nar/gki233}
}

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