The EcoCyc and MetaCyc databases

EcoCyc is an organism-specific Pathway/Genome Database that describes the metabolic and signal-transduction pathways of Escherichia coli, its enzymes, and-a new addition-its transport proteins. MetaCyc is a new metabolic-pathway database that describes pathways and enzymes of many different organisms, with a microbial focus. Both databases are queried using the Pathway Tools graphical user interface, which provides a wide variety of query operations and visualization tools. EcoCyc and MetaCyc are available at http://ecocyc.PangeaSystems.com/ecocyc/     

MetaCyc and AraCyc. Metabolic pathway databases for plant research

MetaCyc (http://metacyc.org) contains experimentally determined biochemical pathways to be used as a reference database for metabolism. In conjunction with the Pathway Tools software, MetaCyc can be used to computationally predict the metabolic pathway complement of an annotated genome. To increase the breadth of pathways and enzymes, more than 60 plant-specific pathways have been added or updated in MetaCyc recently. In contrast to MetaCyc, which contains metabolic data for a wide range of organisms, AraCyc is a species-specific database containing only enzymes and pathways found in the model plant Arabidopsis (Arabidopsis thaliana). AraCyc (http://arabidopsis.org/tools/aracyc/) was the first computationally predicted plant metabolism database derived from MetaCyc. Since its initial computational build, AraCyc has been under continued curation to enhance data quality and to increase breadth of pathway coverage. Twenty-eight pathways have been manually curated from the literature recently. Pathway predictions in AraCyc have also been recently updated with the latest functional annotations of Arabidopsis genes that use controlled vocabulary and literature evidence. AraCyc currently features 1,418 unique genes mapped onto 204 pathways with 1,156 literature citations. The Omics Viewer, a user data visualization and analysis tool, allows a list of genes, enzymes, or metabolites with experimental values to be painted on a diagram of the full pathway map of AraCyc. Other recent enhancements to both MetaCyc and AraCyc include implementation of an evidence ontology, which has been used to provide information on data quality, expansion of the secondary metabolism node of the pathway ontology to accommodate curation of secondary metabolic pathways, and enhancement of the cellular component ontology for storing and displaying enzyme and pathway locations within subcellular compartments.     

The UAB Proteomics Database

SUMMARY: The University of Alabama at Birmingham (UAB) Proteomics Database (UPD) (http://www.uab.edu/proteinmenu) was created to provide a repository for the storage and linkage of two-dimensional (2D) gel images and the associated information obtained through mass spectrometry analysis of the proteins excised from the 2D gels in a manner similar to the SWISS-2DPAGE database and the Stanford Microarray Database. This was accomplished through the development of a web interface, a relational database, image maps and hyperlinks stored in the database. In addition to the internally generated data, UPD provides links to the National Center for Biotechnology Information via accession number hyperlinks. UPD currently contains information on 44 individual proteins derived from four experiments conducted by four UAB faculty members. Images of the gels from which each of these proteins was isolated are accessed by hyperlinks embedded in the database. AVAILABILITY: The UAB Proteomics Database can be accessed at http://www.uab.edu/proteinmenu.     

The Human Papillomavirus Database

Papillomaviruses are responsible for a variety of diseases in humans and animals, ranging from harmless skin warts to lethal cancers. They also make up one of the most genetically diversified families of viruses known, and could represent a model system of DNA-virus evolution. A specialized genetic sequences database, The Human Papillomavirus Database and Analysis Project, was recently established in an effort to provide database services that are specific to papillomaviruses to the research community and to perform a variety of sequence-based analyses. This review is intended to present the scope of the information currently contained in the database and to outline some of the analyses that have been performed on the genetic sequences. These analyses will address issues including phylogenetic relationships, recombination events, selective pressures on different genes and the possibility of cross-species transmission in the case of the papillomaviruses.     

The ITS2 Database

The internal transcribed spacer 2 (ITS2) has been used as a phylogenetic marker for more than two decades. As ITS2 research mainly focused on the very variable ITS2 sequence, it confined this marker to low-level phylogenetics only. However, the combination of the ITS2 sequence and its highly conserved secondary structure improves the phylogenetic resolution¹ and allows phylogenetic inference at multiple taxonomic ranks, including species delimitation^2-8.The ITS2 Database⁹ presents an exhaustive dataset of internal transcribed spacer 2 sequences from NCBI GenBank¹¹ accurately reannotated¹⁰. Following an annotation by profile Hidden Markov Models (HMMs), the secondary structure of each sequence is predicted. First, it is tested whether a minimum energy based fold¹² (direct fold) results in a correct, four helix conformation. If this is not the case, the structure is predicted by homology modeling¹³. In homology modeling, an already known secondary structure is transferred to another ITS2 sequence, whose secondary structure was not able to fold correctly in a direct fold.The ITS2 Database is not only a database for storage and retrieval of ITS2 sequence-structures. It also provides several tools to process your own ITS2 sequences, including annotation, structural prediction, motif detection and BLAST¹⁴ search on the combined sequence-structure information. Moreover, it integrates trimmed versions of 4SALE^15,16 and ProfDistS¹⁷ for multiple sequence-structure alignment calculation and Neighbor Joining¹⁸ tree reconstruction. Together they form a coherent analysis pipeline from an initial set of sequences to a phylogeny based on sequence and secondary structure.In a nutshell, this workbench simplifies first phylogenetic analyses to only a few mouse-clicks, while additionally providing tools and data for comprehensive large-scale analyses.     

The Stanford Microarray Database

The Stanford Microarray Database (SMD) stores raw and normalized data from microarray experiments, and provides web interfaces for researchers to retrieve, analyze and visualize their data. The two immediate goals for SMD are to serve as a storage site for microarray data from ongoing research at Stanford University, and to facilitate the public dissemination of that data once published, or released by the researcher. Of paramount importance is the connection of microarray data with the biological data that pertains to the DNA deposited on the microarray (genes, clones etc.). SMD makes use of many public resources to connect expression information to the relevant biology, including SGD [Ball,C.A., Dolinski,K., Dwight,S.S., Harris,M.A., Issel-Tarver,L., Kasarskis,A., Scafe,C.R., Sherlock,G., Binkley,G., Jin,H. et al. (2000) Nucleic Acids Res., 28, 77-80], YPD and WormPD [Costanzo,M.C., Hogan,J.D., Cusick,M.E., Davis,B.P., Fancher,A.M., Hodges,P.E., Kondu,P., Lengieza,C., Lew-Smith,J.E., Lingner,C. et al. (2000) Nucleic Acids Res., 28, 73-76], Unigene [Wheeler,D.L., Chappey,C., Lash,A.E., Leipe,D.D., Madden,T.L., Schuler,G.D., Tatusova,T.A. and Rapp,B.A. (2000) Nucleic Acids Res., 28, 10-14], dbEST [Boguski,M.S., Lowe,T.M. and Tolstoshev,C.M. (1993) Nature Genet., 4, 332-333] and SWISS-PROT [Bairoch,A. and Apweiler,R. (2000) Nucleic Acids Res., 28, 45-48] and can be accessed at http://genome-www.stanford.edu/microarray.     

The Structure Superposition Database

The need for new tools for investigating biological systems on a large scale is becoming acute, particularly with respect to computationally intensive analyses such as comparisons of many three-dimensional protein structures. Structure superposition is a valuable approach for understanding evolutionary relationships and for the prediction of function. But while available tools are adequate for generating and viewing superpositions of single pairs of protein structures, these tools are generally too cumbersome and time-consuming for examining multiple superpositions. To address this need, we have created the Structure Superposition Database (SSD) for accessing, viewing and understanding large sets of structure superposition data. The initial implementation of the SSD contains the results of pairwise, all-by-all superpositions of a representative set of 115 (beta/alpha)8 barrel structures (TIM barrels). Future plans call for extending the database to include representative structure superpositions for many additional folds. The SSD can be browsed with a user interface module developed as an extension to Chimera, an extensible molecular modeling program. Features of the user interface module facilitate viewing multiple superpositions together. The SSD interface module can be downloaded from http://ssd.rbvi.ucsf.edu.     

The Radiation Hybrid Database.

Since July 1995, the European Bioinformatics Institute (EBI) has maintained RHdb (http://www.ebi.ac.uk/RHdb/RHdb.html ), a public database for radiation hybrid data. Radiation hybrid mapping is an important technique for determining high resolution maps. Recently, CORBA access has been added to Rhdb. The EBI is an Outstation of the European Molecular Biology Laboratory (EMBL).     

The UCSC Genome Browser Database

The University of California Santa Cruz (UCSC) Genome Browser Database is an up to date source for genome sequence data integrated with a large collection of related annotations. The database is optimized to support fast interactive performance with the web-based UCSC Genome Browser, a tool built on top of the database for rapid visualization and querying of the data at many levels. The annotations for a given genome are displayed in the browser as a series of tracks aligned with the genomic sequence. Sequence data and annotations may also be viewed in a text-based tabular format or downloaded as tab-delimited flat files. The Genome Browser Database, browsing tools and downloadable data files can all be found on the UCSC Genome Bioinformatics website (http://genome.ucsc.edu), which also contains links to documentation and related technical information.     

The Protein Mutant Database.

Currently the protein mutant database (PMD) contains over 81 000 mutants, including artificial as well as natural mutants of various proteins extracted from about 10 000 articles. We recently developed a powerful viewing and retrieving system (http://pmd.ddbj.nig.ac.jp), which is integrated with the sequence and tertiary structure databases. The system has the following features: (i) mutated sequences are displayed after being automatically generated from the information described in the entry together with the sequence data of wild-type proteins integrated. This is a convenient feature because it allows one to see the position of altered amino acids (shown in a different color) in the entire sequence of a wild-type protein; (ii) for those proteins whose 3D structures have been experimentally determined, a 3D structure is displayed to show mutation sites in a different color; (iii) a sequence homology search against PMD can be carried out with any query sequence; (iv) a summary of mutations of homologous sequences can be displayed, which shows all the mutations at a certain site of a protein, recorded throughout the PMD.     

The Ribonuclease P Database.

Ribonuclease P is the endoribonuclease responsible for the removal of leader sequences from tRNA precursors. Ribonuclease P is a ribonucleoprotein, and in bacteria the RNA alone is capable of pre-tRNA processing in vitro, i.e. it is a catalytic RNA. The Ribonuclease P Database is a compilation of ribonuclease P sequences, sequence alignments, secondary structures, three-dimensional models and accessory information, in the form of a hypertext document available via the Worldwide Web.     

The EMBL Nucleotide Sequence Database

The EMBL Nucleotide Sequence Database (aka EMBL-Bank; http://www.ebi.ac.uk/embl/) incorporates, organises and distributes nucleotide sequences from all available public sources. EMBL-Bank is located and maintained at the European Bioinformatics Institute (EBI) near Cambridge, UK. In an international collaboration with DDBJ (Japan) and GenBank (USA), data are exchanged amongst the collaborating databases on a daily basis. Major contributors to the EMBL database are individual scientists and genome project groups. Webin is the preferred web-based submission system for individual submitters, whilst automatic procedures allow incorporation of sequence data from large-scale genome sequencing centres and from the European Patent Office (EPO). Database releases are produced quarterly. Network services allow free access to the most up-to-date data collection via FTP, email and World Wide Web interfaces. EBI’s Sequence Retrieval System (SRS), a network browser for databanks in molecular biology, integrates and links the main nucleotide and protein databases plus many other specialized databases. For sequence similarity searching, a variety of tools (e.g. Blitz, Fasta, BLAST) are available which allow external users to compare their own sequences against the latest data in the EMBL Nucleotide Sequence Database and SWISS-PROT. All resources can be accessed via the EBI home page at http://www.ebi.ac.uk.     

The MUSC DNA Microarray Database

SUMMARY: The Medical University of South Carolina (MUSC) DNA Microarray Database is a web-accessible archive of DNA microarray data. The database was developed using the DNA microarray project/data management system, micro ArrayDB. Annotations for each DNA microarray project and associated cRNA target information are stored in a MySQL relational database and linked to array hybridization data (raw and normalized). At the discretion of investigators, data are placed into the public domain where they can be interrogated and downloaded through a web browser. In addition to serving as an online resource of gene expression data, the MUSC DNA Microarray Database is a model for other academic DNA microarray data repositories. AVAILABILITY: Browsing and downloading of MUSC DNA Microarray Database information can be done after registration at http://proteogenomics.musc.edu/pss/home.php.     

The Ribonuclease P Database.

Ribonuclease P is responsible for the 5'-maturation of tRNA precursors. Ribonuclease P is a ribonucleoprotein, and in bacteria (and some Archaea) the RNA subunit alone is catalytically active in vitro, i.e. it is a ribozyme. The Ribonuclease P Database is a compilation of ribonuclease P sequences, sequence alignments, secondary structures, three-dimensional models and accessory information, available via the World Wide Web at the following URL: http://www.mbio.ncsu.edu/RNaseP/home .html     

The Radiation Hybrid Database.

Since July 1995, the European Bioinformatics Institute (EBI) has maintained RHdb, a public database for radiation hybrid data. Radiation hybrid data are used in the generation of alternative genetic maps as they can include non-polymorphic markers and are also powerful enough to order unresolved genetic clusters of polymorphic STSs. The EBI is an Outstation of the European Molecular Biology Laboratory (EMBL).     

The Ribosomal Database Project.

The Ribosomal Database Project (RDP) is a curated database that offers ribosome-related data, analysis services, and associated computer programs. The offerings include phylogenetically ordered alignments of ribosomal RNA (rRNA) sequences, derived phylogenetic trees, rRNA secondary structure diagrams, and various software for handling, analyzing and displaying alignments and trees. The data are available via anonymous ftp (rdp.life.uiuc.edu), electronic mail (server/rdp.life.uiuc.edu) and gopher (rdpgopher.life.uiuc.edu). The electronic mail server also provides ribosomal probe checking, approximate phylogenetic placement of user-submitted sequences, screening for chimeric nature of newly sequenced rRNAs, and automated alignment.     

The ESID Online Database network

Primary immunodeficiencies (PIDs) belong to the group of rare diseases. The European Society for Immunodeficiencies (ESID), is establishing an innovative European patient and research database network for continuous long-term documentation of patients, in order to improve the diagnosis, classification, prognosis and therapy of PIDs. The ESID Online Database is a web-based system aimed at data storage, data entry, reporting and the import of pre-existing data sources in an enterprise business-to-business integration (B2B). The online database is based on Java 2 Enterprise System (J2EE) with high-standard security features, which comply with data protection laws and the demands of a modern research platform. AVAILABILITY: The ESID Online Database is accessible via the official website (http://www.esid.org/). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.     

The Pfam Protein Families Database

Pfam is a large collection of protein multiple sequence alignments and profile hidden Markov models. Pfam is available on the World Wide Web in the UK at http://www.sanger.ac.uk/Software/Pfam/, in Sweden at http://www.cgb.ki.se/Pfam/, in France at http://pfam.jouy.inra.fr/ and in the US at http://pfam.wustl.edu/. The latest version (6.6) of Pfam contains 3071 families, which match 69% of proteins in SWISS-PROT 39 and TrEMBL 14. Structural data, where available, have been utilised to ensure that Pfam families correspond with structural domains, and to improve domain-based annotation. Predictions of non-domain regions are now also included. In addition to secondary structure, Pfam multiple sequence alignments now contain active site residue mark-up. New search tools, including taxonomy search and domain query, greatly add to the functionality and usability of the Pfam resource.     

The Complex Carbohydrate Structure Database

The Complex Carbohydrate Structure Database (CCSD) and CarbBank, an IBM PC/AT (or compatible) database management system, were created to provide an information system to meet the needs of people interested in carbohydrate science. The CCSD, which presently contains more than 2000 citations, is expected to double in size in the next two years and to include, soon thereafter, all of the published structures of carbohydrates larger than disaccharides.