November 9, 2009

CDD: Database for Interactive Domain Family Analysis

Filed under: Bioinformatics,Computational Biology,Proteomics — Biointelligence: Education,Training & Consultancy Services @ 8:30 am
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Protein domains may be viewed as units in the molecular evolution of proteins and can be organized into an evolutionary classification. The set of protein domains characterized so far appears to describe no more than a few thousand superfamilies, where members of each superfamily are related to each other by common descent. Computational annotation of protein function is generally obtained via sequence similarity: once a close neighbor with known function has been identified, its annotation is copied to the sequence with unknown function. This strategy may work very well in functionally homogeneous families and when applied only for very close neighbors or suspected orthologs, but it is doomed to fail often when domain or protein families are sufficiently diverse and when no close neighbors with known function are available.

NCBI’s conserved domain database (CDD) attempts to collate that set and to organize related domain models in a hierarchical fashion, meant to reflect major ancient gene duplication events and subsequent functional diversification. The conserved domain database (CDD) is part of NCBI’s Entrez database system and serves as a primary resource for the annotation of conserved domain footprints on protein sequences in Entrez.CDD provides a strategy toward a more accurate assessment of such neighbor relationships, similar to approaches termed ‘phylogenomic inference. CDD acknowledges that protein domain families may be very diverse and that they may contain sets of related subfamilies.

In CDD curation, we attempt to detect evidence for duplication and functional divergence in domain families by means of phylogenetic analysis. We record the resulting subfamily structure as a set of explicit models, but limit the analysis to ancient duplication events—several hundred million years in the past, as judged by the taxonomic distribution of protein sequences with particular domain subfamily footprints. CDD provides a search tool employing reverse position-specific BLAST (RPS–BLAST), where query sequences are compared to databases of position-specific score matrices (PSSMs), and E-values are obtained in much the same way as in the widely used PSI-BLAST application.

CDD is hosted here:






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