Abstract
BackgroundAlgorithms of sequence alignment are the key instruments for computer-assisted studies of biopolymers. Obviously, it is important to take into account the "quality" of the obtained alignments, i.e. how closely the algorithms manage to restore the "gold standard" alignment (GS-alignment), which superimposes positions originating from the same position in the common ancestor of the compared sequences. As an approximation of the GS-alignment, a 3D-alignment is commonly used not quite reasonably. Among the currently used algorithms of a pair-wise alignment, the best quality is achieved by using the algorithm of optimal alignment based on affine penalties for deletions (the Smith-Waterman algorithm). Nevertheless, the expedience of using local or global versions of the algorithm has not been studied.ResultsUsing model series of amino acid sequence pairs, we studied the relative "quality" of results produced by local and global alignments versus (1) the relative length of similar parts of the sequences (their "cores") and their nonhomologous parts, and (2) relative positions of the core regions in the compared sequences. We obtained numerical values of the average quality (measured as accuracy and confidence) of the global alignment method and the local alignment method for evolutionary distances between homologous sequence parts from 30 to 240 PAM and for the core length making from 10% to 70% of the total length of the sequences for all possible positions of homologous sequence parts relative to the centers of the sequences.ConclusionWe revealed criteria allowing to specify conditions of preferred applicability for the local and the global alignment algorithms depending on positions and relative lengths of the cores and nonhomologous parts of the sequences to be aligned. It was demonstrated that when the core part of one sequence was positioned above the core of the other sequence, the global algorithm was more stable at longer evolutionary distances and larger nonhomologous parts than the local algorithm. On the contrary, when the cores were positioned asymmetrically, the local algorithm was more stable at longer evolutionary distances and larger nonhomologous parts than the global algorithm. This opens a possibility for creation of a combined method allowing generation of more accurate alignments.
Highlights
Algorithms of sequence alignment are the key instruments for computer-assisted studies of biopolymers
They showed that regions of optimal alignment, recurring most frequently in suboptimal alignments, were very similar to alignments produced by the structural alignment methods
We suggest using a comparison of artificially generated sequences to evaluate the quality of alignment algorithms, because the GS alignment for such sequences is known from the very beginning
Summary
Algorithms of sequence alignment are the key instruments for computer-assisted studies of biopolymers. Among the currently used algorithms of a pair-wise alignment, the best quality is achieved by using the algorithm of optimal alignment based on affine penalties for deletions (the Smith-Waterman algorithm). Pair-wise alignment of amino acid sequences is the main method of comparative protein analysis. Vingron and Argos [11] demonstrated that there was a relationship between conservatism of the optimal global alignment region in a set of suboptimal alignments and its similarity with the structural alignment results. They showed that regions of optimal alignment, recurring most frequently in suboptimal alignments, were very similar to alignments produced by the structural alignment methods
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