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Refining multiple sequence alignments with conserved core regions.

ABSTRACT: Accurate multiple sequence alignments of proteins are very important to several areas of computational biology and provide an understanding of phylogenetic history of domain families, their identification and classification. This article presents a new algorithm, REFINER, that refines a multiple sequence alignment by iterative realignment of its individual sequences with the predetermined conserved core (block) model of a protein family. Realignment of each sequence can correct misalignments between a given sequence and the rest of the profile and at the same time preserves the family's overall block model. Large-scale benchmarking studies showed a noticeable improvement of alignment after refinement. This can be inferred from the increased alignment score and enhanced sensitivity for database searching using the sequence profiles derived from refined alignments compared with the original alignments. A standalone version of the program is available by ftp distribution (ftp://ftp.ncbi.nih.gov/pub/REFINER) and will be incorporated into the next release of the Cn3D structure/alignment viewer.

SUBMITTER: Chakrabarti S

PROVIDER: S-EPMC1463900 | biostudies-literature | 2006

REPOSITORIES: biostudies-literature

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Refining multiple sequence alignments with conserved core regions.

Chakrabarti Saikat S Lanczycki Christopher J CJ Panchenko Anna R AR Przytycka Teresa M TM Thiessen Paul A PA Bryant Stephen H SH

Nucleic acids research 20060517 9

Accurate multiple sequence alignments of proteins are very important to several areas of computational biology and provide an understanding of phylogenetic history of domain families, their identification and classification. This article presents a new algorithm, REFINER, that refines a multiple sequence alignment by iterative realignment of its individual sequences with the predetermined conserved core (block) model of a protein family. Realignment of each sequence can correct misalignments bet ...[more]

PMID: 16707662

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Project description:BACKGROUND:Multiple sequence alignments are used to study gene or protein function, phylogenetic relations, genome evolution hypotheses and even gene polymorphisms. Virtually without exception, all available tools focus on conserved segments or residues. Small divergent regions, however, are biologically important for specific quantitative polymerase chain reaction, genotyping, molecular markers and preparation of specific antibodies, and yet have received little attention. As a consequence, they must be selected empirically by the researcher. AlignMiner has been developed to fill this gap in bioinformatic analyses. RESULTS:AlignMiner is a Web-based application for detection of conserved and divergent regions in alignments of conserved sequences, focusing particularly on divergence. It accepts alignments (protein or nucleic acid) obtained using any of a variety of algorithms, which does not appear to have a significant impact on the final results. AlignMiner uses different scoring methods for assessing conserved/divergent regions, Entropy being the method that provides the highest number of regions with the greatest length, and Weighted being the most restrictive. Conserved/divergent regions can be generated either with respect to the consensus sequence or to one master sequence. The resulting data are presented in a graphical interface developed in AJAX, which provides remarkable user interaction capabilities. Users do not need to wait until execution is complete and can.even inspect their results on a different computer. Data can be downloaded onto a user disk, in standard formats. In silico and experimental proof-of-concept cases have shown that AlignMiner can be successfully used to designing specific polymerase chain reaction primers as well as potential epitopes for antibodies. Primer design is assisted by a module that deploys several oligonucleotide parameters for designing primers "on the fly". CONCLUSIONS:AlignMiner can be used to reliably detect divergent regions via several scoring methods that provide different levels of selectivity. Its predictions have been verified by experimental means. Hence, it is expected that its usage will save researchers' time and ensure an objective selection of the best-possible divergent region when closely related sequences are analysed. AlignMiner is freely available at http://www.scbi.uma.es/alignminer.

Dataset Information

Refining multiple sequence alignments with conserved core regions.

Publications

Refining multiple sequence alignments with conserved core regions.

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