Refining multiple sequence alignments with conserved core regions

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 () and will be incorporated into the next release of the Cn3D structure/alignment viewer

CDD: a Conserved Domain Database for protein classification

The Conserved Domain Database (CDD) is the protein classification component of NCBI's Entrez query and retrieval system. CDD is linked to other Entrez databases such as Proteins, Taxonomy and PubMed®, and can be accessed at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=cdd. CD-Search, which is available at http://www.ncbi.nlm.nih.gov/Structure/cdd/wrpsb.cgi, is a fast, interactive tool to identify conserved domains in new protein sequences. CD-Search results for protein sequences in Entrez are pre-computed to provide links between proteins and domain models, and computational annotation visible upon request. Protein–protein queries submitted to NCBI's BLAST search service at http://www.ncbi.nlm.nih.gov/BLAST are scanned for the presence of conserved domains by default. While CDD started out as essentially a mirror of publicly available domain alignment collections, such as SMART, Pfam and COG, we have continued an effort to update, and in some cases replace these models with domain hierarchies curated at the NCBI. Here, we report on the progress of the curation effort and associated improvements in the functionality of the CDD information retrieval system

State of the art: refinement of multiple sequence alignments

BACKGROUND: Accurate multiple sequence alignments of proteins are very important in computational biology today. Despite the numerous efforts made in this field, all alignment strategies have certain shortcomings resulting in alignments that are not always correct. Refinement of existing alignment can prove to be an intelligent choice considering the increasing importance of high quality alignments in large scale high-throughput analysis. RESULTS: We provide an extensive comparison of the performance of the alignment refinement algorithms. The accuracy and efficiency of the refinement programs are compared using the 3D structure-based alignments in the BAliBASE benchmark database as well as manually curated high quality alignments from Conserved Domain Database (CDD). CONCLUSION: Comparison of performance for refined alignments revealed that despite the absence of dramatic improvements, our refinement method, REFINER, which uses conserved regions as constraints performs better in improving the alignments generated by different alignment algorithms. In most cases REFINER produces a higher-scoring, modestly improved alignment that does not deteriorate the well-conserved regions of the original alignment

State of the art: refinement of multiple sequence alignments

<p>Abstract</p> <p>Correction to Chakrabarti S, Lanczycki CJ, Panchenko AR, Przytycka TM, Thiessen PA and Bryant SH: State of the art: refinement of multiple sequence alignments. BMC Bioinformatics 2006, 7:499.</p