Multiple Sequence Alignment System for Pyrosequencing Reads
BICoB '09 Proceedings of the 1st International Conference on Bioinformatics and Computational Biology
Multiple sequence alignment based on profile alignment of intermediate sequences
RECOMB'07 Proceedings of the 11th annual international conference on Research in computational molecular biology
Conotoxin protein classification using pairwise comparison and amino acid composition: toxin-aam
Proceedings of the 13th annual conference on Genetic and evolutionary computation
Computational Biology and Chemistry
Journal of Parallel and Distributed Computing
Pareto Optimal Pairwise Sequence Alignment
IEEE/ACM Transactions on Computational Biology and Bioinformatics (TCBB)
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Motivation:In recent years, several methods have been proposed for aligning two protein sequence profiles, with reported improvements in alignment accuracy and homolog discrimination versus sequence--sequence methods (e.g. BLAST) and profile--sequence methods (e.g. PSI-BLAST). Profile--profile alignment is also the iterated step in progressive multiple sequence alignment algorithms such as CLUSTALW. However, little is known about the relative performance of different profile--profile scoring functions. In this work, we evaluate the alignment accuracy of 23 different profile--profile scoring functions by comparing alignments of 488 pairs of sequences with identity ≤30% against structural alignments. We optimize parameters for all scoring functions on the same training set and use profiles of alignments from both PSI-BLAST and SAM-T99. Structural alignments are constructed from a consensus between the FSSP database and CE structural aligner. We compare the results with sequence--sequence and sequence--profile methods, including BLAST and PSI-BLAST. Results: We find that profile--profile alignment gives an average improvement over our test set of typically 2--3% over profile--sequence alignment and ∼40% over sequence--sequence alignment. No statistically significant difference is seen in the relative performance of most of the scoring functions tested. Significantly better results are obtained with profiles constructed from SAM-T99 alignments than from PSI-BLAST alignments. Availability: Source code, reference alignments and more detailed results are freely available at http://phylogenomics.berkeley.edu/profilealignment/