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A rapid classification protocol for the CATH Domain Database to support structural genomics.

In order to support the structural genomic initiatives, both by rapidly classifying newly determined structures and by suggesting suitable targets for structure determination, we have recently developed several new protocols for classifying structures in the CATH domain database (http://www.biochem.ucl.ac.uk/bsm/cath). These aim to increase the speed of classification of new structures using fast algorithms for structure comparison (GRATH) and to improve the sensitivity in recognising distant structural relatives by incorporating sequence information from relatives in the genomes (DomainFinder). In order to ensure the integrity of the database given the expected increase in data, the CATH Protein Family Database (CATH-PFDB), which currently includes 25,320 structural domains and a further 160,000 sequence relatives has now been installed in a relational ORACLE database. This was essential for developing more rigorous validation procedures and for allowing efficient querying of the database, particularly for genome analysis. The associated Dictionary of Homologous Superfamilies [Bray,J.E., Todd,A.E., Pearl,F.M.G., Thornton,J.M. and Orengo,C.A. (2000) Protein Eng., 13, 153-165], which provides multiple structural alignments and functional information to assist in assigning new relatives, has also been expanded recently and now includes information for 903 homologous superfamilies. In order to improve coverage of known structures, preliminary classification levels are now provided for new structures at interim stages in the classification protocol. Since a large proportion of new structures can be rapidly classified using profile-based sequence analysis [e.g. PSI-BLAST: Altschul,S.F., Madden,T.L., Schaffer,A.A., Zhang,J., Zhang,Z., Miller,W. and Lipman,D.J. (1997) Nucleic Acids Res., 25, 3389-3402], this provides preliminary classification for easily recognisable homologues, which in the latest release of CATH (version 1.7) represented nearly three-quarters of the non-identical structures.

Computational Biology↗

ACTIVITY: a database on DNA/RNA sites activity adapted to apply sequence-activity relationships from one system to another.

ACTIVITY is a database on DNA/RNA site sequences with known activity magnitudes, measurement systems, sequence-activity relationships under fixed experimental conditions and procedures to adapt these relationships from one measurement system to another. This database deposits information on DNA/RNA affinities to proteins and cell nuclear extracts, cutting efficiencies, gene transcription activity, mRNA translation efficiencies, mutability and other biological activities of natural sites occurring within promoters, mRNA leaders, and other regulatory regions in pro- and eukaryotic genomes, their mutant forms and synthetic analogues. Since activity magnitudes are heavily system-dependent, the current version of ACTIVITY is supplemented by three novel sub-databases: (i) SYSTEM, measurement systems; (ii) KNOWLEDGE, sequence-activity relationships under fixed experimental conditions; and (iii) CROSS_TEST, procedures adapting a relationship from one measurement system to another. These databases are useful in molecular biology, pharmacogenetics, metabolic engineering, drug design and biotechnology. The databases can be queried using SRS and are available through the Web, http://wwwmgs. bionet.nsc.ru/systems/Activity/.

Binding Sites↗

Human Immunodeficiency Virus Reverse Transcriptase and Protease Sequence Database: an expanded data model integrating natural language text and sequence analysis programs.

The HIV Reverse Transcriptase and Protease Sequence Database is an on-line relational database that catalogs evolutionary and drug-related sequence variation in the human immunodeficiency virus (HIV) reverse transcriptase (RT) and protease enzymes, the molecular targets of anti-HIV therapy (http://hivdb.stanford.edu). The database contains a compilation of nearly all published HIV RT and protease sequences, including submissions from International Collaboration databases and sequences published in journal articles. Sequences are linked to data about the source of the sequence sample and the antiretroviral drug treatment history of the individual from whom the isolate was obtained. During the past year 3500 sequences have been added and the data model has been expanded to include drug susceptibility data on sequenced isolates. Database content has also been integrated with didactic text and the output of two sequence analysis programs.

Amino Acid Sequence↗

rSNP_Guide, a database system for analysis of transcription factor binding to target sequences: application to SNPs and site-directed mutations.

rSNP_Guide is a novel curated database system for analysis of transcription factor (TF) binding to target sequences in regulatory gene regions altered by mutations. It accumulates experimental data on naturally occurring site variants in regulatory gene regions and site-directed mutations. This database system also contains the web tools for SNP analysis, i.e., active applet applying weight matrices to predict the regulatory site candidates altered by a mutation. The current version of the rSNP_Guide is supplemented by six sub-databases: (i) rSNP_DB, on DNA-protein interaction caused by mutation; (ii) SYSTEM, on experimental systems; (iii) rSNP_BIB, on citations to original publications; (iv) SAMPLES, on experimentally identified sequences of known regulatory sites; (v) MATRIX, on weight matrices of known TF sites; (vi) rSNP_Report, on characteristic examples of successful rSNP_Tools implementation. These databases are useful for the analysis of natural SNPs and site-directed mutations. The databases are available through the Web, http://wwwmgs.bionet.nsc.ru/mgs/systems/rsnp/.

Binding Sites↗

CKAAPs DB: a conserved key amino acid positions database.

The Conserved Key Amino Acid Positions DataBase (CKAAPs DB) provides access to an analysis of structurally similar proteins with dissimilar sequences where key residues within a common fold are identified. The derivation and significance of CKAAPs starting from pairwise structure alignments is described fully in Reddy et al. [Reddy,B.V.B., Li,W.W., Shindyalov,I.N. and Bourne,P.E. (2000) PROTEINS:, in press]. The CKAAPs identified from this theoretical analysis are provided to experimentalists and theoreticians for potential use in protein engineering and modeling. It has been suggested that CKAAPs may be crucial features for protein folding, structural stability and function. Over 170 substructures, as defined by the Combinatorial Extension (CE) database, which are found in approximately 3000 representative polypeptide chains have been analyzed and are available in the CKAAPs DB. CKAAPs DB also provides CKAAPs of the representative set of proteins derived from the CE and FSSP databases. Thus the database contains over 5000 representative poly-peptide chains, covering all known structures in the PDB. A web interface to a relational database permits fast retrieval of structure-sequence alignments, CKAAPs and associated statistics. Users may query by PDB ID, protein name, function and Enzyme Classification number. Users may also submit protein alignments of their own to obtain CKAAPs. An interface to display CKAAPs on each structure from a web browser is also being implemented. CKAAPs DB is maintained by the San Diego Supercomputer Center and accessible at the URL http://ckaaps.sdsc.edu.

Algorithms↗

Database resources of the National Center for Biotechnology Information: 2002 update.

In addition to maintaining the GenBank nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides data analysis and retrieval resources that operate on the data in GenBank and a variety of other biological data made available through NCBI's web site. NCBI data retrieval resources include Entrez, PubMed, LocusLink and the Taxonomy Browser. Data analysis resources include BLAST, Electronic PCR, OrfFinder, RefSeq, UniGene, HomoloGene, Database of Single Nucleotide Polymorphisms (dbSNP), Human Genome Sequencing, Human MapViewer, Human inverted exclamation markVMouse Homology Map, Cancer Chromosome Aberration Project (CCAP), Entrez Genomes, Clusters of Orthologous Groups (COGs) database, Retroviral Genotyping Tools, SAGEmap, Gene Expression Omnibus (GEO), Online Mendelian Inheritance in Man (OMIM), the Molecular Modeling Database (MMDB) and the Conserved Domain Database (CDD). Augmenting many of the web applications are custom implementations of the BLAST program optimized to search specialized data sets. All of the resources can be accessed through the NCBI home page at http://www.ncbi.nlm.nih.gov.

Amino Acid Sequence↗

VirOligo: a database of virus-specific oligonucleotides.

VirOligo is a database of virus-specific oligonucleotides. The VirOligo database consists of two tables, Common data and Oligo data. The Oligo data table contains PCR primers and hybridization probes used for detection of viral nucleic acids and the Common data table contains the experimental conditions used in their detection. Each oligonucleotide entry contains links to PubMed, GenBank, NCBI Taxonomy databases and BLAST. As of July 2001, the VirOligo database contains a complete listing of oligonucleotides specific to viral agents associated with bovine respiratory disease that were published in English in peer-reviewed journals. The viruses are bovine herpes virus types 1, 3, 4 and 5, bovine viral diarrhea virus, bovine parainfluenza 3 virus, bovine respiratory syncytial virus, bovine adenovirus, bovine rhinovirus, bovine coronavirus, bovine reovirus, bovine enterovirus and alcelaphine herpesvirus-1. The VirOligo database is being expanded to other viruses and can be accessed through the Internet at http://viroligo.okstate.edu/.

Animals↗

MMDB: Entrez's 3D-structure database.

Three-dimensional structures are now known within many protein families and it is quite likely, in searching a sequence database, that one will encounter a homolog with known structure. The goal of Entrez's 3D-structure database is to make this information, and the functional annotation it can provide, easily accessible to molecular biologists. To this end Entrez's search engine provides three powerful features. (i) Sequence and structure neighbors; one may select all sequences similar to one of interest, for example, and link to any known 3D structures. (ii) Links between databases; one may search by term matching in MEDLINE, for example, and link to 3D structures reported in these articles. (iii) Sequence and structure visualization; identifying a homolog with known structure, one may view molecular-graphic and alignment displays, to infer approximate 3D structure. In this article we focus on two features of Entrez's Molecular Modeling Database (MMDB) not described previously: links from individual biopolymer chains within 3D structures to a systematic taxonomy of organisms represented in molecular databases, and links from individual chains (and compact 3D domains within them) to structure neighbors, other chains (and 3D domains) with similar 3D structure. MMDB may be accessed at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure.

Animals↗

AraC-XylS database: a family of positive transcriptional regulators in bacteria.

The AraC-XylS database contains information about a family of positive transcriptional regulators broadly distributed in bacteria. This specific database focuses on protein sequences and on the biological and functional features of each of the proteins that belong to this family. Each entry provides information on the protein itself, the annotated protein sequence and, when the crystal is available, a comprehensive representation of its three-dimensional structure. The organization of the database is based on an exhaustive analysis of the scientific literature. The data are interconnected and linked with other databases. Multiple alignments of the members of the family, an extensive collection of references and a tutorial about the family provide additional information. The AraC-XylS database is accessible on the World Wide Web at http://www.AraC-XylS.org.

Amino Acid Sequence↗

DBTSS: DataBase of human Transcriptional Start Sites and full-length cDNAs.

Although the information of cDNAs is indispensable for analyzing gene function, most of the cDNA sequences stored in current databases are imperfect in the sense that they lack the precise information of 5' end termini. To overcome this difficulty, we have developed the oligo-capping method to obtain full-length cDNAs, the information of which has been partly deposited in public databases. In this study, we further constructed human cDNA libraries enriched in clones containing the cap structure to systematically explore the 5' end structure of expressed genes. Of approximately 217 402 5' end sequences obtained, 111 382 have been matched to cDNA sequences of known genes (7889 genes) and are presented in our new database, DataBase of Transcriptional Start Sites (DBTSS; http://elmo.ims.u-tokyo.ac.jp/dbtss/). Sequence comparison between our entries and those of a reference sequence database, RefSeq, revealed that 4683 (34%) of RefSeq sequences should be extended towards the 5' ends. We also mapped each sequence on the human draft genome sequence to identify its transcriptional start site, which provides us with more detailed information on distribution patterns of transcriptional start sites and adjacent regulatory regions.

5' Flanking Region↗

The Histone Database.

Histone proteins are often noted for their high degree of sequence conservation. It is less often recognized that the histones are a heterogeneous protein family. Furthermore, several classes of non-histone proteins containing the histone fold motif exist. Novel histone and histone fold protein sequences continue to be added to public databases every year. The Histone Database (http://genome.nhgri.nih.gov/histones/) is a searchable, periodically updated collection of histone fold-containing sequences derived from sequence-similarity searches of public databases. Sequence sets are presented in redundant and non-redundant FASTA form, hotlinked to GenBank sequence files. Partial sequences are also now included in the database, which has considerably augmented its taxonomic coverage. Annotated alignments of full-length non-redundant sets of sequences are now available in both web-viewable (HTML) and downloadable (PDF) formats. The database also provides summaries of current information on solved histone fold structures, post-translational modifications of histones, and the human histone gene complement.

Amino Acid Motifs↗

tGRAP, the G-protein coupled receptors mutant database.

The searchable mutant database tGRAP (previously called tinyGRAP) at the University of Tromsø contains data on mutated G-protein coupled receptors (GPCRs). All data have been extracted from scientific papers and entered manually into the database. The current version of the tGRAP mutant database (tGRAP.uit.no, release 10, April 2001) contains around 10 500 mutants extracted from almost 1400 research papers containing mutant data on five families of GPCRs, i.e. Family A, rhodopsin-like; Family B, secretin-like; Family C, metabotropic glutamate-like; Family D, pheromone; Family E, cAMP receptors. A query form provides rapid and simple access to relevant mutant information. In addition to this query form, a tool that enables the user to access mutation data via sequence alignments has been introduced. The ability to access mutant data from such alignments increases the usefulness of the mutant database and facilitates comparison of mutagenesis data between receptors. Moreover, this tool allows the construction of tailor-made sequence alignment views from any combination of receptors belonging to the same class. The database is available at http://tGRAP.uit.no/.

Amino Acid Sequence↗

AngioDB: database of angiogenesis and angiogenesis-related molecules.

Angiogenesis is the formation of new capillaries sprouting from pre-existing vessels. Angiogenesis occurs in a variety of normal physiological and pathological conditions and is regulated by a balance of stimulatory and inhibitory angiogenic factors. The control of this balance may fail and result in the formation of a pathologic capillary network during the development of many diseases. Therefore, we developed the angiogenesis database (AngioDB), which can provide a signaling network of angiogenesis-related biomolecules in human. Each record of AngioDB consisted of 12 fields and was developed by using a relational database management system. For the retrieval of data, Active Server Page (ASP) technology was integrated in this system. Users can access the database by a query or imagemap browsing program. The retrieving system also provides a list of angiogenesis-related molecules classified by three categories, and the database has an external link to NCBI databases. AngioDB is available via the Internet at http://angiodb.snu.ac.kr/.

Amino Acid Sequence↗

MICdb: database of prokaryotic microsatellites.

The MICdb (Microsatellites Database) (http://www.cdfd.org.in/micas) is a comprehensive relational database of non-redundant microsatellites extracted from fully sequenced prokaryotic genomes. The current version (1.0) of the database has been compiled from 83 genomes belonging to different phylogenetic groups. This database has been linked to MICAS, the web-based Microstatellite Analysis Server. MICAS provides a user-friendly front-end to systematically extract data on microsatellite tracts from genomes. The database contains the following information pertaining to the microsatellites: the regions (coding/non-coding, if coding, their GenBank annotations) containing microsatellite tracts; the frequencies of their occurrences, the size and the number of repeating motifs; and the sequences of the tracts. MICAS also provides an interface to Autoprimer, a primer design program to automatically design primers for selected microsatellite loci.

DNA Primers↗

The Nuclear Protein Database (NPD): sub-nuclear localisation and functional annotation of the nuclear proteome.

The Nuclear Protein Database (NPD) is a curated database that contains information on more than 1300 vertebrate proteins that are thought, or are known, to localise to the cell nucleus. Each entry is annotated with information on predicted protein size and isoelectric point, as well as any repeats, motifs or domains within the protein sequence. In addition, information on the sub-nuclear localisation of each protein is provided and the biological and molecular functions are described using Gene Ontology (GO) terms. The database is searchable by keyword, protein name, sub-nuclear compartment and protein domain/motif. Links to other databases are provided (e.g. Entrez, SWISS-PROT, OMIM, PubMed, PubMed Central). Thus, NPD provides a gateway through which the nuclear proteome may be explored. The database can be accessed at http://npd.hgu.mrc.ac.uk and is updated monthly.

Amino Acid Sequence↗

Database resources of the National Center for Biotechnology.

In addition to maintaining the GenBank(R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides data analysis and retrieval resources for the data in GenBank and other biological data made available through NCBI's Web site. NCBI resources include Entrez, PubMed, PubMed Central (PMC), LocusLink, the NCBITaxonomy Browser, BLAST, BLAST Link (BLink), Electronic PCR (e-PCR), Open Reading Frame (ORF) Finder, References Sequence (RefSeq), UniGene, HomoloGene, ProtEST, Database of Single Nucleotide Polymorphisms (dbSNP), Human/Mouse Homology Map, Cancer Chromosome Aberration Project (CCAP), Entrez Genomes and related tools, the Map Viewer, Model Maker (MM), Evidence Viewer (EV), Clusters of Orthologous Groups (COGs) database, Retroviral Genotyping Tools, SAGEmap, Gene Expression Omnibus (GEO), Online Mendelian Inheritance in Man (OMIM), the Molecular Modeling Database (MMDB), the Conserved Domain Database (CDD), and the Conserved Domain Architecture Retrieval Tool (CDART). Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. All of the resources can be accessed through the NCBI home page at: http://www.ncbi.nlm.nih.gov.

Animals↗

GrainGenes, the genome database for small-grain crops.

GrainGenes, http://www.graingenes.org, is the international database for the wheat, barley, rye and oat genomes. For these species it is the primary repository for information about genetic maps, mapping probes and primers, genes, alleles and QTLs. Documentation includes such data as primer sequences, polymorphism descriptions, genotype and trait scoring data, experimental protocols used, and photographs of marker polymorphisms, disease symptoms and mutant phenotypes. These data, curated with the help of many members of the research community, are integrated with sequence and bibliographic records selected from external databases and results of BLAST searches of the ESTs. Records are linked to corresponding records in other important databases, e.g. Gramene's EST homologies to rice BAC/PACs, TIGR's Gene Indices and GenBank. In addition to this information within the GrainGenes database itself, the GrainGenes homepage at http://wheat.pw.usda.gov provides many other community resources including publications (the annual newsletters for wheat, barley and oat, monographs and articles), individual datasets (mapping and QTL studies, polymorphism surveys, variety performance evaluations), specialized databases (Triticeae repeat sequences, EST unigene sets) and pages to facilitate coordination of cooperative research efforts in specific areas such as SNP development, EST-SSRs and taxonomy. The goal is to serve as a central point for obtaining and contributing information about the genetics and biology of these cereal crops.

Alleles↗

IMGT/HLA and IMGT/MHC: sequence databases for the study of the major histocompatibility complex.

The IMGT/HLA database (http://www.ebi.ac.uk/imgt/hla) has provided a centralized repository for the sequences of the alleles named by the WHO Nomenclature Committee for Factors of the HLA System for the past four years. Since its initial release the database has grown and is the primary source of information for the study of sequences of the human major histocompatibilty complex. The initial release of the database contained a limited number of tools. As a result of feedback from our users and developments in HLA we have been able to provide new tools and facilities. The HLA sequences have also been extended to include intron sequences and the 3' and 5' untranslated regions in the alignments and also the inclusion of new genes such as MICA. The IMGT/MHC database (http://www.ebi.ac.uk/imgt/mhc) was released in March 2002 to provide a similar resource for other species. The first release of IMGT/MHC contains the sequences of non-human primates (apes, new and old world monkeys), canines and feline sequences. Further species will be added shortly and the database aims to become the primary source of MHC data for non-human sequences.

Alleles↗