Systematic exploration of guide-tree topology effects for small protein alignments

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Title: Systematic exploration of guide-tree topology effects for small protein alignments
Authors: Sievers, Fabian
Hughes, Graham
Higgins, D. (Des)
Permanent link: http://hdl.handle.net/10197/7309
Date: 4-Oct-2014
Abstract: Background: Guide-trees are used as part of an essential heuristic to enable the calculation of multiple sequence alignments. They have been the focus of much method development but there has been little effort at determining systematically, which guide-trees, if any, give the best alignments. Some guide-tree construction schemes are based on pair-wise distances amongst unaligned sequences. Others try to emulate an underlying evolutionary tree and involve various iteration methods. Results: We explore all possible guide-trees for a set of protein alignments of up to eight sequences. We find that pairwise distance based default guide-trees sometimes outperform evolutionary guide-trees, as measured by structure derived reference alignments. However, default guide-trees fall way short of the optimum attainable scores. On average chained guide-trees perform better than balanced ones but are not better than default guide-trees for small alignments. Conclusions: Alignment methods that use Consistency or hidden Markov models to make alignments are less susceptible to sub-optimal guide-trees than simpler methods, that basically use conventional sequence alignment between profiles. The latter appear to be affected positively by evolutionary based guide-trees for difficult alignments and negatively for easy alignments. One phylogeny aware alignment program can strongly discriminate between good and bad guide-trees. The results for randomly chained guide-trees improve with the number of sequences.
Funding Details: Science Foundation Ireland
Type of material: Journal Article
Publisher: BioMed Central
Copyright (published version): 2014 the Authors
Keywords: Multiple sequence alignmentGuide-tree topologyAlignment accuracyBenchmarking
DOI: 10.1186/1471-2105-15-338
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
Medicine Research Collection

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