LIGAND: chemical database for enzyme reactions

MOTIVATION: The existing molecular biology databases focus on the sequence and structural aspects of biological macromolecules, i.e. DNAs, RNAs and proteins. However, in order to understand the functional aspects, it is essential to computerize the interaction of these molecules. Furthermore, living cells contain additional molecules, such as metabolic compounds and metal ions, that may also be considered as parts of the basic building blocks of life, but are not well organized in public databases. LIGAND chemical database is our attempt to solve these problems, at least for enzymatic reactions. RESULTS: LIGAND consists of two sections: ENZYME and COMPOUND. The ENZYME section is an extension of previous studies (Suyama et al. , Comput. Applic. Biosci., 9, 9-15, 1993), and it is a flat-file representation of 3303 enzymes and 2976 enzymatic reactions in the chemical equation format that can be parsed by machine. The COMPOUND section has been newly constructed for information on the nomenclature and chemical structures of compounds. It contains 5383 chemical compounds. Both ENZYME and COMPOUND entries contain rich cross-reference information, most of which is automatically generated by the DBGET/LinkDB system, thus providing the linkage between chemical and biological databases. LIGAND is updated daily, tightly coupled with the KEGG metabolic pathway database, and forms the basis for reconstruction and computation of pathways. AVAILABILITY: LIGAND can be accessed through the DBGET/LinkDB and KEGG systems in the Japanese GenomeNet database service via http://www.genome.ad.jp/. The flat-file format of the LIGAND database can be downloaded by anonymous FTP via ftp://kegg. genome.adjp/molecules/ligand/. CONTACT: goto@kuicr.kyoto-u.ac.jp; nishioka@scl.kyoto-u.ac.jp; kanehisa@kuicr.kyoto-u.ac.jp     

AAindex: Amino Acid Index Database

AAindex is a database of numerical indices representing various physicochemical and biochemical properties of amino acids and pairs of amino acids. It consists of two sections: AAindex1 for the amino acid index of 20 numerical values and AAindex2 for the amino acid mutation matrix of 210 numerical values. Each entry of either AAindex1 or AAindex2 consists of the definition, the reference information, a list of related entries in terms of the correlation coefficient, and the actual data. The database may be accessed through the DBGET/LinkDB system at GenomeNet (http://www.genome.ad. jp/dbget/) or may be downloaded by anonymous FTP (ftp://ftp.genome. ad.jp/db/genomenet/aaindex/).     

The ENZYME data bank in 1999

The ENZYME data bank is a repository of information related to the nomenclature of enzymes. In recent years it has become an indispensable resource for the development of metabolic databases. The current version contains information on 3704 enzymes. It is available through the ExPASy WWW server (http://www.expasy.ch/).     

The University of Minnesota Biocatalysis/Biodegradation Database: specialized metabolism for functional genomics

The University of Minnesota Biocatalysis/Biodegradation Database (UM-BBD, http://www.labmed.umn.edu/umbbd/i nde x.html) first became available on the web in 1995 to provide information on microbial biocatalytic reactions of, and biodegradation pathways for, organic chemical compounds, especially those produced by man. Its goal is to become a representative database of biodegradation, spanning the diversity of known microbial metabolic routes, organic functional groups, and environmental conditions under which biodegradation occurs. The database can be used to enhance understanding of basic biochemistry, biocatalysis leading to speciality chemical manufacture, and biodegradation of environmental pollutants. It is also a resource for functional genomics, since it contains information on enzymes and genes involved in specialized metabolism not found in intermediary metabolism databases, and thus can assist in assigning functions to genes homologous to such less common genes. With information on >400 reactions and compounds, it is poised to become a resource for prediction of microbial biodegradation pathways for compounds it does not contain, a process complementary to predicting the functions of new classes of microbial genes.     

Histone Sequence Database: sequences, structures, post-translational modifications and genetic loci

The Histone Sequence Database is an annotated and searchable collection of all available histone and histone fold sequences and structures. Particular emphasis has been placed on documenting conflicts between similar sequence entries from a number of source databases, conflicts that are not necessarily documented in the source databases themselves. New additions to the database include compilations of post-translational modifications for each of the core and linker histones, as well as genomic information in the form of map loci for the human histone gene complement, with the genetic loci linked to Online Mendelian Inheritance in Man (OMIM). The database is freely accessible through the World Wide Web at either http://genome.nhgri.nih.gov/histones/ or http://www.ncbi.nlm.nih. gov/Baxevani/HISTONES     

Gene recognition by combination of several gene-finding programs

MOTIVATION: A number of programs have been developed to predict the eukaryotic gene structures in DNA sequences. However, gene finding is still a challenging problem. RESULTS: We have explored the effectiveness when the results of several gene-finding programs were re-analyzed and combined. We studied several methods with four programs (FEXH, GeneParser3, GEN-SCAN and GRAIL2). By HIGHEST-policy combination method or BOUNDARY method, approximate correlation (AC) improved by 3-5% in comparison with the best single gene-finding program. From another viewpoint, OR-based combination of the four programs is the most reliable to know whether a candidate exon overlaps with the real exon or not, although it is less sensitive than GENSCAN for exon-intron boundaries. Our methods can easily be extended to combine other programs. AVAILABILITY: We have developed a server program (Shirokane System) and a client program (GeneScope) to use the methods. GeneScope is available through a WWW site (http://gf.genome.ad.jp/). CONTACT: (katsu,takagi)@ims.u-tokyo.ac.jp     

The modified bitegard: a method for administering supplemental oxygen and measuring carbon dioxide

HUGE is a database for human large proteins newly identified by Kazusa cDNA project, which aims to predict protein primary structures from sequences of human large cDNAs (>4 kb). In particular, cDNA clones capable of coding for large proteins (>50 kDa) are current targets of the project. More than 700 sequences of human cDNAs (average size, 5.1 kb) have been determined to date and deposited in the public databases. Notable information implied from the cDNAs and the predicted protein sequences can be obtained through HUGE via the World Wide Web at URL http://www.kazusa.or.jp/huge     

Serum amyloid A induces chemotaxis of human mast cells by activating a pertussis toxin-sensitive signal transduction pathway

Human MitBASE is a database collecting human mtDNA variants. This database is part of a greater mitochondrial genome database (MitBASE) funded within the EU Biotech Program. The present paper reports the recent improvements in data structure, data quality and data quantity. As far as the database structure is concerned it is now fully designed and implemented. Based on the previously described structure some changes have been made to optimise both data input and data quality. Cross-references with other bio-databases (EMBL, OMIM, MEDLINE) have been implemented. Human MitBASE data can be queried with the MitBASE Simple Query System (http://www.ebi.ac.uk/htbin/Mitbase/mit base.pl) and with SRS at the EBI under the 'Mutation' section (http://srs.ebi.ac.uk/srs5/). At present the HumanMitBASE node contains approximately 5000 variants related to studies investigating population polymorphisms and pathologies.     

Nucleic acid-based cross-linking assay for detection and quantification of hepatitis B virus DNA

Small nucleolar RNAs (snoRNAs) are involved in cleavage of rRNA, modification of rRNA nucleotides and, perhaps, other aspects of ribosome biogenesis in eukaryotic cells. Scores of snoRNAs have been discovered in recent years from various eukaryotes, and the total number is predicted to be up to 200 different snoRNA species per individual organism. We have created a comprehensive database for snoRNAs from the yeast Saccharomyces cerevisiae which allows easy access to detailed information about each species known (almost 70 snoRNAs are featured). The database consists of three major parts: (i) a utilities section; (ii) a master table; and (iii) a collection of tables for the individual snoRNAs. The utilities section provides an introduction to the database. The master table lists all known S. cerevisiae snoRNAs and their major properties. Information in the individual tables includes: alternate names, size, family classification, genomic organization, sequences (with major features identified), GenBank accession numbers, occurrence of homologues, gene disruption phenotypes, functional properties and associated RNAs and proteins. All information is accompanied with appropriate literature references. The database is available on the World Wide Web (http://www.bio.umass. edu/biochem/rna-sequence/Yeast_snoRNA_Database/snoRNA_ DataBase.html), and should be useful for a wide range of snoRNA studies.     

Keio Mutation Database for eye disease genes (KMeyeDB)

A database of mutations in human eye disease genes has been constructed. This KMeyeDB employs a database software MutationView which provides graphical data presentation and analysis as a smooth user-interface. Currently, the KMeyeDB contains mutation data of 16 different genes for 18 eye diseases. The KMeyeDB is accessible through http://mutview.dmb.med.keio.ac.jp with advanced internet browsers.     

Effects of fluoxetine and dothiepin on 24-hour activity in depressed patients

The Munich Information Center for Protein Sequences (MIPS-GSF), Martinsried near Munich, Germany, develops and maintains genome oriented databases. It is commonplace that the amount of sequence data available increases rapidly, but not the capacity of qualified manual annotation at the sequence databases. Therefore, our strategy aims to cope with the data stream by the comprehensive application of analysis tools to sequences of complete genomes, the systematic classification of protein sequences and the active support of sequence analysis and functional genomics projects. This report describes the systematic and up-to-date analysis of genomes (PEDANT), a comprehensive database of the yeast genome (MYGD), a database reflecting the progress in sequencing the Arabidopsis thaliana genome (MATD), the database of assembled, annotated human EST clusters (MEST), and the collection of protein sequence data within the framework of the PIR-International Protein Sequence Database (described elsewhere in this volume). MIPS provides access through its WWW server (http://www.mips.biochem.mpg.de) to a spectrum of generic databases, including the above mentioned as well as a database of protein families (PROTFAM), the MITOP database, and the all-against-all FASTA database.     

Tips for preventing esophageal variceal bleeding

The Protein Information Resource (PIR) has been maintaining a database of curated protein sequence alignments since 1991. The collection includes superfamily, family and homology domain alignments. CLUSTAL V/W is used to generate multiple sequence alignments and ALNED, an interactive alignment editor, is used to check and correct them. The database has helped in classifying sequences, in defining new homology domains, and in spreading and standardizing protein names, features and keywords among members of a family or superfamily. The ATLAS information retrieval system can be used to browse and query the PIR-ALN alignments. The quarterly and weekly updates can be accessed via the WWW at http://www-nbrf. georgetown.edu/pir/     

UTRdb: a specialized database of 5'- and 3'-untranslated regions of eukaryotic mRNAs

The important role the untranslated regions of eukaryotic mRNAs may play in gene regulation and expression is now widely acknowledged. For this reason we developed UTRdb, a specialized database of 5'- and 3'-untranslated sequences of eukaryotic mRNAs cleaned from redundancy. UTRdb entries are enriched with specialized information not present in the primary databases, including the presence of functional patterns already demonstrated by experimental analysis to have some functional role. A collection of such patterns is being collected in UTRsite database (http://bio-www.ba.cnr.it:8000/srs5/) which can also be used with appropriate computational tools to detect known functional patterns contained in mRNA untranslated regions.     

Prostatic abscess caused by anaerobic germs

The system SOSUI for the discrimination of membrane proteins and soluble ones together with the prediction of transmembrane helices was developed, in which the accuracy of the classification of proteins was 99% and the corresponding value for the transmembrane helix prediction was 97%. AVAILABILITY: The system SOSUI is available through internet access: http://www.tuat.ac.jp/mitaku/sosui/. CONTACT: sosui@biophys.bio.tuat. ac.jp.     

Indigo: a World-Wide-Web review of genomes and gene functions

The present article describes a genome database reviewing gene-related knowledge of two model bacteria, Bacillus subtilis and Escherichia coli. The database, Indigo, is open through the World-Wide Web (http://indigo.genetique.uvsq.fr). The concept used for organising the data, the concept of neighbourhood, allows one to explore the database content in an efficient although somewhat unusual way. Here, genes are related to each other by a variety of neighbourhoods, including proximity in the chromosome, phylogenetic kinship, participation in a common metabolic pathway, common presence in an article of the literature, or similar use of the genetic code. Several examples illustrate how this concept of neighbourhood permits one to review the available knowledge about a given gene or gene family, and elaborate unexpected, but revealing, analyses about gene functions.     

Structural analysis of Arabidopsis thaliana chromosome 5. VII. Sequence features of the regions of 1,013,767 bp covered by sixteen physically assigned P1 and TAC clones

Sixteen P1 and TAC clones assigned to Arabidopsis thaliana chromosome 5 were sequenced, and their sequence features were analyzed using various computer programs. The total length of the sequences determined was 1,013,767 bp. Together with the nucleotide sequences of 109 clones previously reported, the regions of chromosome 5 sequenced so far now total 9,072,622 bp, which presumably covers approximately one-third of the chromosome. A similarity search against the reported gene sequences predicted the presence of a total of 225 protein-coding genes and/or gene segments in the newly sequenced regions, indicating an average gene density of one gene per 4.5 kb. Introns were identified in 72.4% of the potential protein genes for which the entire gene structure was predicted, and the average number per gene and the average length of the introns were 3.3 and 163 bp, respectively. These sequence features are essentially identical to those in the previously reported sequences. The sequence data and gene information are available on the World Wide Web database KAOS (Kazusa Arabidopsis data Opening Site) at http://www.kazusa.or.jp/arabi/.     

IMGT, the International ImMunoGeneTics database

IMGT, the international ImMunoGeneTics database, is an integrated database specialising in Immunoglobulins (Ig), T cell Receptors (TcR) and Major Histocompatibility Complex (MHC) of all vertebrate species, created by Marie-Paule Lefranc, CNRS, Montpellier II University, Montpellier, France (lefranc@ligm.crbm.cnrs-mop.fr). IMGT includes three databases: LIGM-DB (for Ig and TcR), MHC/HLA-DB and PRIMER-DB (the last two in development). IMGT comprises expertly annotated sequences and alignment tables. LIGM-DB contains more than 23 000 Immunoglobulin and T cell Receptor sequences from 78 species. MHC/HLA-DB contains Class I and Class II Human Leucocyte Antigen alignment tables. An IMGT tool, DNAPLOT, developed for Ig, TcR and MHC sequence alignments, is also available. IMGT works in close collaboration with the EMBL database. IMGT goals are to establish a common data access to all immunogenetics data, including nucleotide and protein sequences, oligonucleotide primers, gene maps and other genetic data of Ig, TcR and MHC molecules, and to provide a graphical user friendly data access. IMGT has important implications in medical research (repertoire in autoimmune diseases, AIDS, leukemias, lymphomas), therapeutical approaches (antibody engineering), genome diversity and genome evolution studies. IMGT is freely available at http://imgt.cnusc.fr:8104     

Natural ligand of mouse CD1d1: cellular glycosylphosphatidylinositol

Mouse CD1d1, a member of the CD1 family of evolutionarily conserved major histocompatibility antigen-like molecules, controls the differentiation and function of a T lymphocyte subset, NK1+ natural T cells, proposed to regulate immune responses. The CD1d1 crystal structure revealed a large hydrophobic binding site occupied by a ligand of unknown chemical nature. Mass spectrometry and metabolic radiolabeling were used to identify cellular glycosylphosphatidylinositol as a major natural ligand of CD1d1. CD1d1 bound glycosylphosphatidylinositol through its phosphatidylinositol aspect with high affinity. Glycosylphosphatidylinositol or another glycolipid could be a candidate natural ligand for CD1d1-restricted T cells.