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Alignment of protein sequences by their profiles.

ABSTRACT: The accuracy of an alignment between two protein sequences can be improved by including other detectably related sequences in the comparison. We optimize and benchmark such an approach that relies on aligning two multiple sequence alignments, each one including one of the two protein sequences. Thirteen different protocols for creating and comparing profiles corresponding to the multiple sequence alignments are implemented in the SALIGN command of MODELLER. A test set of 200 pairwise, structure-based alignments with sequence identities below 40% is used to benchmark the 13 protocols as well as a number of previously described sequence alignment methods, including heuristic pairwise sequence alignment by BLAST, pairwise sequence alignment by global dynamic programming with an affine gap penalty function by the ALIGN command of MODELLER, sequence-profile alignment by PSI-BLAST, Hidden Markov Model methods implemented in SAM and LOBSTER, pairwise sequence alignment relying on predicted local structure by SEA, and multiple sequence alignment by CLUSTALW and COMPASS. The alignment accuracies of the best new protocols were significantly better than those of the other tested methods. For example, the fraction of the correctly aligned residues relative to the structure-based alignment by the best protocol is 56%, which can be compared with the accuracies of 26%, 42%, 43%, 48%, 50%, 49%, 43%, and 43% for the other methods, respectively. The new method is currently applied to large-scale comparative protein structure modeling of all known sequences.

SUBMITTER: Marti-Renom MA

PROVIDER: S-EPMC2280052 | biostudies-literature | 2004 Apr

REPOSITORIES: biostudies-literature

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Alignment of protein sequences by their profiles.

Marti-Renom Marc A MA Madhusudhan M S MS Sali Andrej A

Protein science : a publication of the Protein Society 20040401 4

The accuracy of an alignment between two protein sequences can be improved by including other detectably related sequences in the comparison. We optimize and benchmark such an approach that relies on aligning two multiple sequence alignments, each one including one of the two protein sequences. Thirteen different protocols for creating and comparing profiles corresponding to the multiple sequence alignments are implemented in the SALIGN command of MODELLER. A test set of 200 pairwise, structure- ...[more]

PMID: 15044736

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Project description:BACKGROUND:Rapidly accumulating genome sequence data from multiple species offer powerful opportunities for the detection of DNA sequence evolution. Phylogenetic tree construction and codon-based tests for natural selection are the prevailing tools used to detect functionally important evolutionary change in protein coding sequences. These analyses often require multiple DNA sequence alignments that maintain the correct reading frame for each collection of putative orthologous sequences. Since this feature is not available in most alignment tools, codon reading frames often must be checked manually before evolutionary analyses can commence. RESULTS:Here we report an online codon-preserved alignment tool (OCPAT) that generates multiple sequence alignments automatically from the coding sequences of any list of human gene IDs and their putative orthologs from genomes of other vertebrate tetrapods. OCPAT is programmed to extract putative orthologous genes from genomes and to align the orthologs with the reading frame maintained in all species. OCPAT also optimizes the alignment by trimming the most variable alignment regions at the 5' and 3' ends of each gene. The resulting output of alignments is returned in several formats, which facilitates further molecular evolutionary analyses by appropriate available software. Alignments are generally robust and reliable, retaining the correct reading frame. The tool can serve as the first step for comparative genomic analyses of protein-coding gene sequences including phylogenetic tree reconstruction and detection of natural selection. We aligned 20,658 human RefSeq mRNAs using OCPAT. Most alignments are missing sequence(s) from at least one species; however, functional annotation clustering of the ~1700 transcripts that were alignable to all species shows that genes involved in multi-subunit protein complexes are highly conserved. CONCLUSION:The OCPAT program facilitates large-scale evolutionary and phylogenetic analyses of entire biological processes, pathways, and diseases.

Dataset Information

Alignment of protein sequences by their profiles.

Publications

Alignment of protein sequences by their profiles.

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