Manual curation in the Conserved Domain Database
Creators: name: Gonzales, Noreen
name: Chitsaz, Farideh
name: Derbyshire, Myra
name: Geer, Lewis
name: Gwadz, Marc
name: Lianyi Han
name: He, Jane
name: Hurwitz, David
name: Lanczycki, Christopher
name: Lu, Fu
name: Marchler, Gabriele
name: Song, James
name: Narmada Thanki
name: Wang, Josie
name: Yamashita, Roxanne
name: Chanjuan Zheng
name: Bryant, Steve
name: Marchler-Bauer, Aron
Publisher: name: F1000Research
Year: 2016

description: The Conserved Domain Database (CDD) is a collection of multiple sequence alignments that represent ancient conserved domains. One part of the CDD resource is a mirror of publicly available domain model collections, including Pfam, SMART, TIGRFAM, the NCBI Protein Clusters resource, and COGs. These models are used as seed alignments to produce the second part of the CDD resource, manually-curated conserved domain models (cd accession numbers) arranged in a hierarchical structure to reflect an evolutionary classification of ancient protein domain families. A curated model contains a description of the domain, Pubmed links to review articles, and annotation of features that are conserved across the domain family. These annotations are supported by evidence observed in 3D structures as well as by published literature. Curated domain family models are also created de-novo for previously uncharacterized families, identified by 3D structures with no conserved domain hits. Hierarchical classification and curation of protein domains, facilitated by using our in-house tools CDTree (hierarchy viewer) and Cn3D (structure viewer and multiple alignment editor), have been the focus of our manual curation efforts. In addition, we develop structural domain models (sd accessions) to represent protein sequence segments (such as short repeats, coiled coils, and transmembrane regions) not well covered by classical domain models. We also manually validate superfamily clusters (cl accession numbers), formed by an automated procedure, which are sets of conserved domain models that generate overlapping annotation on the same protein sequences. Superfamily clustering allows the organization of data within CDD in a non-redundant way, as each data source may have its own model for a specific conserved domain. Cluster validation is aided by using Cytoscape as a visualization tool for the degree of overlap between conserved domain models. More recently, our manual curation efforts are focused on providing functional labels for specific domain architectures, using an in-house procedure called SPARCLE ("Specific ARChitecture Labeling Engine"). While we are able to assign functional labels to a large fraction of proteins, we have also identified areas of insufficient coverage and resolution of the current protein domain models that comprise CDD. In this poster, we will discuss all aspects of manual curation in CDD. The need for manual curation work is always much greater than our available resources and we hope to automate hierarchical classifications to some degree in the near future.<br><br>Acknowledgement<br>This research was supported by the Intramural Research Program of the National Library of Medicine, NIH.<br>