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SUMMARY: DaliLite is a program for pairwise structure comparison and for structure database searching. It is a standalone version of the search engine of the popular Dali server. A web interface is provided to view the results, multiple alignments and 3D superimpositions of structures.
Downloading the information stored in relational databases into XML and other flat formats is a common task in bioinformatics. This periodical dumping of information requires considerable CPU time, disk and memory resources. YAdumper has been developed as a purpose-specific tool to deal with the integral structured information download of relational databases. YAdumper is a Java application that organizes database extraction following an XML template based on an external Document Type Declaration. Compared with other non-native alternatives, YAdumper substantially reduces memory requirements and considerably improves writing performance.
SWISS-PROT is a curated protein sequence database which strives to provide a high level of annotation (such as the description of the function of a protein, its domain structure, post-translational modifications, variants, etc.), a minimal level of redundancy and high level of integration with other databases. Recent developments of the database include: cross-references to additional databases; a variety of new documentation files and improvements to TrEMBL, a computer annotated supplement to SWISS-PROT. TrEMBL consists of entries in SWISS-PROT-like format derived from the translation of all coding sequences (CDS) in the EMBL nucleotide sequence database, except the CDS already included in SWISS-PROT. The URLs for SWISS-PROT on the WWW are: http://www.expasy.ch/sprot and http://www. ebi.ac.uk/sprot
The annotation of protein function has become a crucial problem with the advent of sequence and structural genomics initiatives. A large body of evidence suggests that protein structural information is frequently encoded in local sequences, and that folds are mainly made up of a number of simple local units of super-secondary structural motifs, consisting of a few secondary structures and their connecting loops. Moreover, protein loops play an important role in protein function. Here we present ArchDB, a classification database of structural motifs, consisting of one loop plus its bracing secondary structures. ArchDB currently contains 12,665 super-secondary elements classified into 1496 motif subclasses. The database provides an easy way to retrieve functional information from protein structures sharing a common motif, to search motifs found in a given SCOP family, superfamily or fold, or to search by keywords on proteins with classified loops. The ArchDB database of loops is located at http://sbi.imim.es/archdb.
Chicken B cells create their immunoglobulin repertoire within the Bursa of Fabricius by gene conversion. The high homologous recombination activity is shared by the bursal B-cell-derived DT40 cell line, which integrates transfected DNA constructs at high rates into its endogenous loci. Targeted integration in DT40 is used frequently to analyze the function of genes by gene disruption. In this paper, we describe a large database of >7000 expressed sequence tags (ESTs) from bursal lymphocytes that should be a valuable resource for the identification of gene disruption targets in DT40. ESTs of interest can be recognized easily by online or keyword searches. Because the database reflects the gene expression profile of bursal lymphocytes, it provides valuable hints as to which genes might be involved in B-cell-specific processes related to immunoglobulin repertoire formation, signal transduction, transcription, and apoptosis. This large collection of chicken ESTs will also be useful for gene expression studies and comparative gene mapping within the chicken genome project. Details of the bursal EST sequencing project and access to database search forms can be found on the DT40 web site (http://genetics.hpi.uni-hamburg.de/dt40.html).
To identify unknown proteins from plant peroxisomes, the Arabidopsis genome was screened for proteins with putative major or minor peroxisome targeting signals type 1 or 2 (PTS1 or PTS2), as defined previously (Reumann S [2004] Plant Physiol 135: 783-800). About 220 and 60 proteins were identified that carry a putative PTS1 or PTS2, respectively. To further support postulated targeting to peroxisomes, several prediction programs were applied and the putative targeting domains analyzed for properties conserved in peroxisomal proteins and for PTS conservation in homologous plant expressed sequence tags. The majority of proteins with a major PTS and medium to high overall probability of peroxisomal targeting represent novel nonhypothetical proteins and include several enzymes involved in beta-oxidation of unsaturated fatty acids and branched amino acids, and 2-hydroxy acid oxidases with a predicted function in fatty acid alpha-oxidation, as well as NADP-dependent dehydrogenases and reductases. In addition, large protein families with many putative peroxisomal isoforms were recognized, including acyl-activating enzymes, GDSL lipases, and small thioesterases. Several proteins are homologous to prokaryotic enzymes of a novel aerobic hybrid degradation pathway for aromatic compounds and proposed to be involved in peroxisomal biosynthesis of plant hormones like jasmonic acid, auxin, and salicylic acid. Putative regulatory proteins of plant peroxisomes include protein kinases, small heat shock proteins, and proteases. The information on subcellular targeting prediction, homology, and in silico expression analysis for these Arabidopsis proteins has been compiled in the public database AraPerox to accelerate discovery and experimental investigation of novel metabolic and regulatory pathways of plant peroxisomes.
The mammalian kidney collecting duct plays an important role in the fine regulation of Na, K, water, and acid-base balance. Functional genomic and proteomic studies of the kidney offer new opportunities in the understanding of renal physiology and pathophysiology, and the collecting duct is an appropriate target tissue because of the relative simplicity of its cells and the ease of isolating or culturing large numbers of collecting duct cells. Study of the collecting duct includes assessment of gene expression and protein regulation and abundance. For example, DNA and protein microarrays can be used to quantitate gene expression and protein regulation and abundance under varying physiological conditions. An Internet-accessible database has been devised for major collecting duct proteins involved in transport and regulation of cellular processes. The individual proteins included in this database are those culled from literature searches and from previously published studies involving cDNA arrays and serial analysis of gene expression (SAGE). Design of microarray targets for the study of kidney collecting duct tissues is facilitated by the database, which includes links to curated base pair and amino acid sequence data, relevant literature, and related databases. Use of the database is illustrated by a search for water channel proteins, aquaporins, and by a subsequent search for vasopressin receptors. Links are shown to the literature and to sequence data for human, rat, and mouse, as well as to relevant web-based resources. Extension of the database is dynamic and is done through a maintenance interface. This permits creation of new categories, updating of existing entries, and addition of new ones.
The Type 1 Diabetes Genetics Consortium (T1DGC) is an international, multicenter program organized to promote research to identify genes and their alleles that determine an individual's risk for type 1 diabetes (T1D). The primary goal of the T1DGC is to establish resources and data that can be used by, and that is fully accessible to, the research community in the study of T1D. All the information on T1DGC can be accessed at the following web address: http://www.t1dgc.org. A resource base of well-characterized families is being assembled that will facilitate the localization and characterization of T1D susceptibility genes. From these families, the T1DGC is establishing banks of DNA, serum, plasma, and cell lines, as well as useful databases. The T1DGC also sponsors training opportunities (bioinformatics) and technology transfer (HLA genotyping).
A novel database and modified alignment program is described which provides a fast and accurate procedure for assigning nucleotide sequences to allele types for multi-locus sequence analysis (MLSA). The database has between 40 and 160 alleles per organism including Neisseria meningitidis, Streptococcus pneumoniae, Staphylococcus aureus and Haemophilus influenzae. The database directly compares the query nucleotide sequence against all alleles within the database and this system reduces the time taken for the analysis of nucleotide sequence data and assignment of alleles for subsequent sequence analysis.
EDAS, a database of alternatively spliced human genes, contains data on the alignment of proteins, mRNAs, and EST. It contains information on all exons and introns observed, as well as elementary alternatives formed from them. The database makes it possible to filter the output data by changing the cut-off threshold by the significance level. The database is accessible at http://www.gene-bee.msu.ru/edas/.
In the open-field behavior of rodents, Software for Exploring Exploration (SEE) can be used for an explicit design of behavioral endpoints with high genotype discrimination and replicability across laboratories. This ability is demonstrated here in the development of a measure for darting behavior. The behavior of two common mouse inbred strains, C57BL/6J (B6) and DBA/2J (D2), was analyzed across three different laboratories, and under the effect of cocaine or amphetamine. "Darting" was defined as having higher acceleration during progression segments while moving less during stops. D2 mice darted significantly more than B6 mice in each laboratory, despite being significantly less active. These differences were maintained following cocaine administration (up to 20mg/kg) and only slightly altered by amphetamine (up to 5mg/kg) despite a several fold increase in activity. The replicability of darting behavior was confirmed in additional experiments distinct from those used for its design. The strategy leading to the darting measure may be used to develop additional discriminative and replicable endpoints of open-field behavior.
There is a pressing need for interactive bioinformatics tools that empower investigators with the means to extract information and organize it in a simplified but meaningful format. A wealth of mammalian gene expression data is readily accessible, much of which is based on expressed sequence tags (ESTs). Many mammalian ESTs are derived from tissue-specific cDNA libraries in which the number of ESTs representing a specific gene approximates the transcriptional expression level in the source tissue. Our program ExQuest (Expressional Quantification of ESTs) organizes the public EST database (dbEST) into hierarchical tissue classes and reports tissue or developmental gene expression patterns for both mRNA and genomic sequences. ExQuest also displays tissue expression patterns of genes in the context of assembled chromosomes. These interactive "transcriptome" maps provide a novel tool for investigating the genomic basis of gene expression as well as prioritizing candidate genes within genetically mapped mutant and quantitative trait loci.
The exponential discovery rate of new genomic alterations, leading to inherited disorders, as well as the need for comparative studies of different population's mutation frequencies necessitates recording their population-wide spectrum in online mutation databases. We report the construction of the Hellenic National Mutation database (http://www.goldenhelix.org/hellenic), a prototype database derived from a multicenter academic initiative, aiming to provide high quality and up-to-date information on the underlying genetic heterogeneity of inherited disorders found in the Hellenic population. Database records include informative summaries of the various genetic disorders studied in the Hellenic population, focused in particular on their incidence in Greece, a comprehensive reference list, and a well-structured query interface, which provides easy access to the list of the different mutations responsible for the inherited disorders in the Hellenic population. Also, extensive links to the respective Online Mendelian Inheritance in Man (OMIM) entries and, when available, to the locus-specific databases are provided, so that the user can retrieve the maximum amount of information from a single website. Furthermore, the Hellenic National Mutation database design allows easy data entry and curation. Creation of the Hellenic National Mutation database will significantly facilitate molecular diagnosis of inherited disorders in Greece and will motivate further investigation of yet unknown genetic diseases in the Hellenic population.
Bioinformatics is playing an increasingly important role in nearly all aspects of drug discovery, drug assessment, and drug development. This growing importance lies not only in the role that bioinformatics plays in handling large volumes of data, but also in the utility of bioinformatics tools to predict, analyze, or help interpret clinical and preclinical findings. This review focuses on describing and evaluating some of the newer or more important bioinformatics resources (i.e., databases and software) that are of growing importance to understanding or predicting drug metabolism, especially with respect to the absorption, distribution, metabolism, excretion, (ADME), and toxicity (T) of both existing drugs and potential drug leads. Detailed descriptions and critical assessments of a number of potentially useful bioinformatics/cheminformatics databases and predictive ADMET software tools are provided. Additionally, several pharmaceutically important applications of both the databases and software are highlighted. Given the rapid growth in this area and the rapid changes that are taking place, a special emphasis is placed on freely available or Web-accessible resources.
UNLABELLED: BioABACUS (Biotechnology AB breviation and A cronym U ncovering Service) a new, searchable, cross-referenced, database of abbreviations and acronyms in biotechnology and computer science is described. AVAILABILITY: BioABACUS is accessible over the World Wide Web at http://www.nmsu.edu/molbio/bioABACUShome.htm. CONTACT: mrimer@nmsu.edu,moconnel@nmsu.edu
MOTIVATION: What constitutes a baseline level of success for protein fold recognition methods? As fold recognition benchmarks are often presented without any thought to the results that might be expected from a purely random set of predictions, an analysis of fold recognition baselines is long overdue. Given varying amounts of basic information about a protein-ranging from the length of the sequence to a knowledge of its secondary structure-to what extent can the fold be determined by intelligent guesswork? Can simple methods that make use of secondary structure information assign folds more accurately than purely random methods and could these methods be used to construct viable hierarchical classifications? EXPERIMENTS PERFORMED: A number of rapid automatic methods which score similarities between protein domains were devised and tested. These methods ranged from those that incorporated no secondary structure information, such as measuring absolute differences in sequence lengths, to more complex alignments of secondary structure elements. Each method was assessed for accuracy by comparison with the Class Architecture Topology Homology (CATH) classification. Methods were rated against both a random baseline fold assignment method as a lower control and FSSP as an upper control. Similarity trees were constructed in order to evaluate the accuracy of optimum methods at producing a classification of structure. RESULTS: Using a rigorous comparison of methods with CATH, the random fold assignment method set a lower baseline of 11% true positives allowing for 3% false positives and FSSP set an upper benchmark of 47% true positives at 3% false positives. The optimum secondary structure alignment method used here achieved 27% true positives at 3% false positives. Using a less rigorous Critical Assessment of Structure Prediction (CASP)-like sensitivity measurement the random assignment achieved 6%, FSSP-59% and the optimum secondary structure alignment method-32%. Similarity trees produced by the optimum method illustrate that these methods cannot be used alone to produce a viable protein structural classification system. CONCLUSIONS: Simple methods that use perfect secondary structure information to assign folds cannot produce an accurate protein taxonomy, however they do provide useful baselines for fold recognition. In terms of a typical CASP assessment our results suggest that approximately 6% of targets with folds in the databases could be assigned correctly by randomly guessing, and as many as 32% could be recognised by trivial secondary structure comparison methods, given knowledge of their correct secondary structures.
Clinical GeneOrganizer (CGO) is a novel windows-based archiving, organization and data mining software for the integration of gene expression profiling in clinical medicine. The program implements various user-friendly tools and extracts data for further statistical analysis. This software was written for Affymetrix GeneChip *.txt files, but can also be used for any other microarray-derived data. The MS-SQL server version acts as a data mart and links microarray data with clinical parameters of any other existing database and therefore represents a valuable tool for combining gene expression analysis and clinical disease characteristics.
The EyeSite is a web-based database of protein families for proteins that function in the eye and their homologous sequences. The resource clusters proteins at different levels of homology in order to facilitate functional annotation of sequences and modelling of proteins from structural homologues. Eye proteins are organized into the tissue types in which they function and are clustered into homologous families using a novel protocol employing the TribeMCL algorithm. Homologous families are further subdivided into sequence clusters for which multiple sequence alignments are generated. Structural annotations from the CATH domain database are provided for nearly 90% of the sequences, and protein family annotations from the Pfam database for approximately 86%. Homology models have also been generated where appropriate. The EyeSite is stored in a relational database and is extensively linked to other online bioinformatics resources to help relate allelic variants, annotations and clinical details to the derived data in the database. The EyeSite is available for online search, sequence information and model retrieval at http://eyesite.cryst.bbk.ac.uk/.