Probalign: Multiple sequence alignment using partition function posterior probabilities

Document Type

Article

Publication Date

11-15-2006

Abstract

Motivation: The maximum expected accuracy optimization criterion for multiple sequence alignment uses pairwise posterior probabilities of residues to align sequences. The partition function methodology is one way of estimating these probabilities. Here, we combine these two ideas for the first time to construct maximal expected accuracy sequence alignments. Results: We bridge the two techniques within the program Probalign. Our results indicate that Probalign alignments are generally more accurate than other leading multiple sequence alignment methods (i.e. Probcons, MAFFT and MUSCLE) on the BAliBASE 3.0 protein alignment benchmark. Similarly, Probalign also outperforms these methods on the HOMSTRAD and OXBENCH benchmarks. Probalign ranks statistically highest (P-value < 0.005) on all three benchmarks. Deeper scrutiny of the technique indicates that the improvements are largest on datasets containing N/C-terminal extensions and on datasets containing long and heterogeneous length proteins. These points are demonstrated on both real and simulated data. Finally, our method also produces accurate alignments on long and heterogeneous length datasets containing protein repeats. Here, alignment accuracy scores are at least 10% and 15% higher than the other three methods when standard deviation of length is >300 and 400, respectively. © 2006 Oxford University Press.

Identifier

33751004142 (Scopus)

Publication Title

Bioinformatics

External Full Text Location

https://doi.org/10.1093/bioinformatics/btl472

e-ISSN

13674811

ISSN

13674803

PubMed ID

16954142

First Page

2715

Last Page

2721

Issue

22

Volume

22

Grant

EF0331654

Fund Ref

National Science Foundation

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