An Overview of Multiple Sequence Alignment

Victor Simossis1, Jens Kleinjung1, Jaap Heringa1

1 Integrative Bioinformatics Institute (IBIVU), Free University, Amsterdam
Publication Name:  Current Protocols in Bioinformatics
Unit Number:  Unit 3.7
DOI:  10.1002/0471250953.bi0307s03
Online Posting Date:  November, 2003
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Multiple sequence alignment is perhaps the most commonly applied bioinformatics technique. It often leads to fundamental biological insight into sequence‐structure‐function relationships of nucleotide or protein sequence families. In this unit, an overview of multiple sequence alignment techniques is presented, covering a history of nearly 30 years from the early pioneering methods to the current state‐of‐the‐art techniques. Methodological and biological issues and end‐user considerations, as well as alignment evaluation issues, are discussed.

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Table of Contents

  • MSA Methodology
  • MSA Methods
  • Assessment of MSA
  • Conclusion
  • Literature Cited
  • Figures
  • Tables
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Literature Cited

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Key References
   Dayhoff et al., 1978. See above.
  This atlas represents a seminal approach to sequence alignment. The evolutionary model that is still used today in most methods is introduced here, together with the now classical PAM series of amino acid exchange matrices. The evolutionary model is often referred to as the Dayhoff model, while the most widely used early matrix in the PAM series, the PAM250 matrix, is commonly known as the Dayhoff matrix.
   Felsenstein, 1981. See above.
  In this paper, the important evolutionary method of maximum likelihood is introduced. The method, which attempts to find the tree that maximizes the probability that the observed data will fit the tree under a given evolutionary model, is now generally accepted as the most accurate strategy.
   Hogeweg and Hesper, 1984. See above.
  This paper introduces the progressive multiple alignment strategy, which is still the most widely used multiple alignment technique. In this early paper, alignment iteration is already addressed. Another interesting feature of the paper is the use of so‐called internode sequences, which are additionally inferred sequences ancestral to subgroups of sequences in the phylogenetic tree calculated for the query sequence set.
   Needleman and Wunsch, 1970. See above.
  This is one of the most quoted early papers on sequence alignment. In this paper, the global dynamic programming algorithm is introduced to the biological community and applied to pairwise amino acid sequences. The basic dynamic programming algorithm had been conceived before by the physicist Richard Belman, who published a large series of papers and books on the topic during the 1950s and 60s.
   Smith and Waterman, 1981. See above.
  Following the approach by Needleman and Wunsch (), Smith and Waterman derived the now classical algorithm for local pair‐wise sequence alignment. Most widely used homology search engines such as BLAST are fast approximations of the Smith and Waterman algorithm and perform local alignment.
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