Multiple Sequence Alignment Black and White

22-Mar-12
INTRODUCTION
• MULTIPLE SEQUENCE ALIGNMENT aligns multiple related
sequences to achieve optimal matching of the sequences.
MULTIPLE SEQUENCE • Related sequences are identified through the database similarity
searching.
ALIGNMENT • As the process generates multiple matching sequence pairs, it is

often necessary to convert the numerous pairwise alignments into
a single alignment, which arranges sequences in such a way that
evolutionarily equivalent positions across all sequences are
matched.
ADVANTAGES OF MSA SCORING FUNCTION

• Multiple Sequence Alignment reveals more biological information • Multiple sequence alignment arranges sequences in such a way that
than many pairwise alignments can. a maximum number of residues from each sequence are matched
up according to a particular scoring function.
• For example, it allows the identification of conserved sequence
patterns and motifs in the whole sequence family, which are not • The scoring function for multiple sequence alignment is based on
obvious to detect by comparing only two sequences. the concept of sum of pairs (SP).
– SP is the sum of the scores of all possible pairs of sequences in a multiple
• Many conserved and functionally critical amino acid residues can be alignment based on a particular scoring matrix.
identified in a protein multiple alignment.
• In calculating the SP scores, each column is scored by summing the
• MSA is also an essential prerequisite to carrying out phylogenetic scores for all possible pairwise matches, mismatches and gap costs.
analysis of sequence families and prediction of protein secondary
and tertiary structures. • The score of the entire alignment is the sum of all of the column
scores.
• Multiple sequence alignment also has applications in designing
degenerate polymerase chain reaction (PCR) primers based on • The purpose of most multiple sequence alignment algorithms is to
multiple related sequences. achieve maximum SP scores..
EXHAUSTIVE AND HEURISTIC PROGRAMS Progressive Alignment Method

• The exhaustive alignment method involves examining all possible • Progressive alignment depends on the stepwise assembly of
aligned positions simultaneously. multiple alignment and is heuristic in nature.
– It speeds up the alignment of multiple sequences through a multistep
• Similar to dynamic programming in pairwise alignment, which process.
involves the use of a two-dimensional matrix to search for an
optimal alignment, to use dynamic programming for multiple • It first conducts pairwise alignments for each possible pair of
sequence alignment, extra dimensions are needed to take all
sequences using the Needleman–Wunsch global alignment method
possible ways of sequence matching into consideration.
– This means to establish a multidimensional search matrix.
and records these similarity scores from the pairwise comparisons.
– For instance, for three sequences, a three-dimensional matrix is required to – The scores can either be percent identity or similarity scores based on a
account for all possible alignment scores. particular substitution matrix.
– Both scores correlate with the evolutionary distances between sequences.
– The scores are then converted into evolutionary distances to generate a
distance matrix for all the sequences involved.
• The heuristic algorithms fall into three categories: progressive
alignment type, iterative alignment type, and block-based alignment • Clustal (www.ebi.ac.uk/clustalw/) has two variants, ClustalW and
type.
ClustalX.
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Iterative Alignment Block-Based Alignment

• The procedure starts by producing a low-quality alignment and • The progressive and iterative alignment strategies are largely global
gradually improves it by iterative realignment through well-defined alignment based. They may therefore fail to recognize conserved domains
procedures until no more improvements in the alignment scores can and motifs among highly divergent sequences of varying lengths.
be achieved. – The block-based alignment identifies a block of un-gapped alignment shared by all the
sequences, hence, the block-based local alignment strategy.
• EXAMPLES
• DIALIGN2 (http://bioweb.pasteur.fr/seqanal/interfaces/dialign2.html) is a web
based program designed to detect local similarities.
– The method breaks each of the sequences down to smaller segments and performs all
possible pairwise alignments between the segments.
– High-scoring segments, called blocks, among different sequences are then compiled in
a progressive manner to assemble a full multiple alignment.
• Match-Box (www.sciences.fundp.ac.be/biologie/bms/matchbox submit.shtml).
Web based server for block based alignment
– The program compares segments of every nine residues of all possible pairwise
alignments.
– The server requires the user to submit a set of sequences in the FASTA format and the
results are returned by e-mail.

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22-Mar-12

ALIGNMENT • As the process generates multiple matching sequence pairs, it is

ADVANTAGES OF MSA SCORING FUNCTION

EXHAUSTIVE AND HEURISTIC PROGRAMS Progressive Alignment Method

Iterative Alignment Block-Based Alignment

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