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PubMed2005

DictyMOLD-a Dictyostelium discoideum genome browser database.

UNLABELLED: With the Dictyostelium Genome Project nearing completion, we initiated the construction of a data repository for all Dictyostelium discoideum genomic data. Up to now this database, called DictyMOLD (Dicty Map Of Linked Data), incorporates the recently completed D.discoideum chromosomes 1 and 2 sequences together with related annotations. To visualise maps, sequences and annotations and to provide access for the scientific community a perl-based browser was developed. AVAILABILITY: The DictyMOLD database is freely accessible via http://genome.imb-jena.de/dictyostelium/ CONTACT: gernot@imb-jena.de.

Animals↗

PubMed2005

Use of within-array replicate spots for assessing differential expression in microarray experiments.

MOTIVATION: Spotted arrays are often printed with probes in duplicate or triplicate, but current methods for assessing differential expression are not able to make full use of the resulting information. The usual practice is to average the duplicate or triplicate results for each probe before assessing differential expression. This results in the loss of valuable information about genewise variability. RESULTS: A method is proposed for extracting more information from within-array replicate spots in microarray experiments by estimating the strength of the correlation between them. The method involves fitting separate linear models to the expression data for each gene but with a common value for the between-replicate correlation. The method greatly improves the precision with which the genewise variances are estimated and thereby improves inference methods designed to identify differentially expressed genes. The method may be combined with empirical Bayes methods for moderating the genewise variances between genes. The method is validated using data from a microarray experiment involving calibration and ratio control spots in conjunction with spiked-in RNA. Comparing results for calibration and ratio control spots shows that the common correlation method results in substantially better discrimination of differentially expressed genes from those which are not. The spike-in experiment also confirms that the results may be further improved by empirical Bayes smoothing of the variances when the sample size is small. AVAILABILITY: The methodology is implemented in the limma software package for R, available from the CRAN repository http://www.r-project.org

Algorithms↗

PubMed2005

Concept-based annotation of enzyme classes.

MOTIVATION: Given the explosive growth of biomedical data as well as the literature describing results and findings, it is getting increasingly difficult to keep up to date with new information. Keeping databases synchronized with current knowledge is a time-consuming and expensive task-one which can be alleviated by automatically gathering findings from the literature using linguistic approaches. We describe a method to automatically annotate enzyme classes with disease-related information extracted from the biomedical literature for inclusion in such a database. RESULTS: Enzyme names for the 3901 enzyme classes in the BRENDA database, a repository for quantitative and qualitative enzyme information, were identified in more than 100,000 abstracts retrieved from the PubMed literature database. Phrases in the abstracts were assigned to concepts from the Unified Medical Language System (UMLS) utilizing the MetaMap program, allowing for the identification of disease-related concepts by their semantic fields in the UMLS ontology. Assignments between enzyme classes and diseases were created based on their co-occurrence within a single sentence. False positives could be removed by a variety of filters including minimum number of co-occurrences, removal of sentences containing a negation and the classification of sentences based on their semantic fields by a Support Vector Machine. Verification of the assignments with a manually annotated set of 1500 sentences yielded favorable results of 92% precision at 50% recall, sufficient for inclusion in a high-quality database. AVAILABILITY: Source code is available from the author upon request. SUPPLEMENTARY INFORMATION: ftp.uni-koeln.de/institute/biochemie/pub/brenda/info/diseaseSupp.pdf.

Algorithms↗

PubMed2005

Meta-DP: domain prediction meta-server.

UNLABELLED: Meta-DP, a domain prediction meta-server provides a simple interface to predict domains in a given protein sequence using a number of domain prediction methods. The Meta-DP is a convenient resource because through accessing a single site, users automatically obtain the results of the various domain prediction methods along with a consensus prediction. The Meta-DP is currently coupled to 10 domain prediction servers and can be extended to include any number of methods. Meta-DP can thus become a centralized repository of available methods. Meta-DP was also used to evaluate the performance of 13 domain prediction methods in the context of CAFASP-DP. AVAILABILITY: The Meta-DP server is freely available at http://meta-dp.bioinformatics.buffalo.edu and the CAFASP-DP evaluation results are available at http://cafasp4.bioinformatics.buffalo.edu/dp/update.html CONTACT: hkaur@bioinformatics.buffalo.edu SUPPLEMENTARY INFORMATION: Available at http://cafasp4.bioinformatics.buffalo.edu/dp/update.html.

Algorithms↗

PubMed2005

ChemDB: a public database of small molecules and related chemoinformatics resources.

MOTIVATION: The development of chemoinformatics has been hampered by the lack of large, publicly available, comprehensive repositories of molecules, in particular of small molecules. Small molecules play a fundamental role in organic chemistry and biology. They can be used as combinatorial building blocks for chemical synthesis, as molecular probes in chemical genomics and systems biology, and for the screening and discovery of new drugs and other useful compounds. RESULTS: We describe ChemDB, a public database of small molecules available on the Web. ChemDB is built using the digital catalogs of over a hundred vendors and other public sources and is annotated with information derived from these sources as well as from computational methods, such as predicted solubility and three-dimensional structure. It supports multiple molecular formats and is periodically updated, automatically whenever possible. The current version of the database contains approximately 4.1 million commercially available compounds and 8.2 million counting isomers. The database includes a user-friendly graphical interface, chemical reactions capabilities, as well as unique search capabilities. AVAILABILITY: Database and datasets are available on http://cdb.ics.uci.edu.

Access to Information↗

PubMed2005

VIS-O-BAC: exploratory visualization of functional genome studies from bacteria.

UNLABELLED: The visualization-aided exploration of complex datasets will allow the research community to formulate novel functional hypotheses leading to a better understanding of biological processes at all levels. Therefore, we have developed a web resource termed VIS-O-BAC designed for the functional investigation of expression data for model systems, such as bacterial pathogens based on a graphical display. Genome-scale datasets derived from typical 'omic' approaches can directly be explored with respect to three biologically relevant aspects, the genome structure (operon organization), the organization of genes in pathways (KEGG) and the gene function with Gene Ontology (GO) terms. The integrated viewers can be used in parallel and combine expression data and functional annotations from different external data repositories. The graphical visualizations evidently accelerate both the validation of regulatory information and the detection of affected biological processes. AVAILABILITY: http://leger2.gbf.de/cgi-bin/vis-o-bac.pl. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Chromosome Mapping↗

PubMed2006

Chemical effects in biological systems (CEBS) object model for toxicology data, SysTox-OM: design and application.

MOTIVATION: The CEBS data repository is being developed to promote a systems biology approach to understand the biological effects of environmental stressors. CEBS will house data from multiple gene expression platforms (transcriptomics), protein expression and protein-protein interaction (proteomics), and changes in low molecular weight metabolite levels (metabolomics) aligned by their detailed toxicological context. The system will accommodate extensive complex querying in a user-friendly manner. CEBS will store toxicological contexts including the study design details, treatment protocols, animal characteristics and conventional toxicological endpoints such as histopathology findings and clinical chemistry measures. All of these data types can be integrated in a seamless fashion to enable data query and analysis in a biologically meaningful manner. RESULTS: An object model, the SysBio-OM (Xirasagar et al., 2004) has been designed to facilitate the integration of microarray gene expression, proteomics and metabolomics data in the CEBS database system. We now report SysTox-OM as an open source systems toxicology model designed to integrate toxicological context into gene expression experiments. The SysTox-OM model is comprehensive and leverages other open source efforts, namely, the Standard for Exchange of Nonclinical Data (http://www.cdisc.org/models/send/v2/index.html) which is a data standard for capturing toxicological information for animal studies and Clinical Data Interchange Standards Consortium (http://www.cdisc.org/models/sdtm/index.html) that serves as a standard for the exchange of clinical data. Such standardization increases the accuracy of data mining, interpretation and exchange. The open source SysTox-OM model, which can be implemented on various software platforms, is presented here. AVAILABILITY: A universal modeling language (UML) depiction of the entire SysTox-OM is available at http://cebs.niehs.nih.gov and the Rational Rose object model package is distributed under an open source license that permits unrestricted academic and commercial use and is available at http://cebs.niehs.nih.gov/cebsdownloads. Currently, the public toxicological data in CEBS can be queried via a web application based on the SysTox-OM at http://cebs.niehs.nih.gov CONTACT: xirasagars@saic.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Computational Biology↗

PubMed2006

REMORA: a pilot in the ocean of BioMoby web-services.

UNLABELLED: Emerging web-services technology allows interoperability between multiple distributed architectures. Here, we present REMORA, a web server implemented according to the BioMoby web-service specifications, providing life science researchers with an easy-to-use workflow generator and launcher, a repository of predefined workflows and a survey system. CONTACT: Jerome.Gouzy@toulouse.inra.fr AVAILABILITY: The REMORA web server is freely available at http://bioinfo.genopole-toulouse.prd.fr/remora, sources are available upon request from the authors.

Computer Graphics↗

PubMed2006

affylmGUI: a graphical user interface for linear modeling of single channel microarray data.

SUMMARY: affylmGUI is a graphical user interface (GUI) to an integrated workflow for Affymetrix microarray data. The user is able to proceed from raw data (CEL files) to QC and pre-processing, and eventually to analysis of differential expression using linear models with empirical Bayes smoothing. Output of the analysis (tables and figures) can be exported to an HTML report. The GUI provides user-friendly access to state-of-the-art methods embodied in the Bioconductor software repository. AVAILABILITY: affylmGUI is an R package freely available from http://www.bioconductor.org. It requires R version 1.9.0 or later and tcl/tk 8.3 or later and has been successfully tested on Windows 2000, Windows XP, Linux (RedHat and Fedora distributions) and Mac OS/X with X11. Further documentation is available at http://bioinf.wehi.edu.au/affylmGUI CONTACT: keith@wehi.edu.au.

Bayes Theorem↗

PubMed2006

CellML2SBML: conversion of CellML into SBML.

UNLABELLED: CellML and SBML are XML-based languages for storage and exchange of molecular biological and physiological reaction models. They use very similar subsets of MathML to specify the mathematical aspects of the models. CellML2SBML is implemented as a suite of XSLT stylesheets that, when applied consecutively, convert models expressed in CellML into SBML without significant loss of information. The converter is based on the most recent stable versions of the languages (CellML version 1.1; SBML Level 2 Version 1), and the XSLT used in the stylesheets adheres to the XSLT version 1.0 specification. Of all 306 models in the CellML repository in April 2005, CellML2SBML converted 91% automatically into SBML. Minor manual changes to the unit definitions in the originals raised the percentage of successful conversions to 96%. AVAILABILITY: http://sbml.org/software/cellml2sbml/. SUPPLEMENTARY INFORMATION: Instructions for use and further documentation available on http://sbml.org/software/cellml2sbml/

Cell Physiological Phenomena↗

PubMed2006

Dynamical analysis of a generic Boolean model for the control of the mammalian cell cycle.

MOTIVATION: To understand the behaviour of complex biological regulatory networks, a proper integration of molecular data into a full-fledge formal dynamical model is ultimately required. As most available data on regulatory interactions are qualitative, logical modelling offers an interesting framework to delineate the main dynamical properties of the underlying networks. RESULTS: Transposing a generic model of the core network controlling the mammalian cell cycle into the logical framework, we compare different strategies to explore its dynamical properties. In particular, we assess the respective advantages and limits of synchronous versus asynchronous updating assumptions to delineate the asymptotical behaviour of regulatory networks. Furthermore, we propose several intermediate strategies to optimize the computation of asymptotical properties depending on available knowledge. AVAILABILITY: The mammalian cell cycle model is available in a dedicated XML format (GINML) on our website, along with our logical simulation software GINsim (http://gin.univ-mrs.fr/GINsim). Higher resolution state transitions graphs are also found on this web site (Model Repository page).

Animals↗

PubMed2006

Babel's tower revisited: a universal resource for cross-referencing across annotation databases.

MOTIVATION: Annotation databases are widely used as public repositories of biological knowledge. However, most of these resources have been developed by independent groups which used different designs and different identifiers for the same biological entities. As we show in this article, incoherent name spaces between various databases represent a serious impediment to using the existing annotations at their full potential. Navigating between various such name spaces by mapping IDs from one database to another is a very important issue which is not properly addressed at the moment. RESULTS: We have developed a web-based resource, Onto-Translate (OT), which effectively addresses this problem. OT is able to map onto each other different types of biological entities from the following annotation databases: Swiss-Prot, TrEMBL, NREF, PIR, Gene Ontology, KEGG, Entrez Gene, GenBank, GenPept, IMAGE, RefSeq, UniGene, OMIM, PDB, Eukaryotic Promoter Database, HUGO Gene Nomenclature Committee and NetAffx. Currently, OT is able to perform 462 types of mappings between 29 different types of IDs from 17 databases concerning 53 organisms. Among these, over 300 types of translations and 15 types of IDs are not currently supported by any other tool or resource. On average, OT is able to correctly map between 96 and 99% of the biological entities provided as input. In terms of speed, sets of approximately 20 000 IDs can be translated in <30 s, in most cases. AVAILABILITY: OT is a part of Onto-Tools, which is freely available at http://vortex.cs.wayne.edu/Projects.html

Database Management Systems↗

PubMed2006

CREMOFAC--a database of chromatin remodeling factors.

MOTIVATION: Chromatin-remodeling is an important event in the eukaryotic nucleus rendering nucleosomal DNA accessible for various transaction processes. Remodeling Factors facilitate the dynamic nature of chromatin through participation of the collective action of (i) ATP and (ii) Non-ATP dependent factors. Considering the importance of these factors in eukaryotes, we have developed, CREMOFAC, a dedicated and frequently updated web-database for chromatin-remodeling factors. RESULTS: The database harbors factors from 49 different organisms reported in literature and facilitates a comprehensive search for them. In addition, it also provides in-depth information for the factors reported in the three widely studied mammals namely, human, mouse and rat. Further, information on literature, pathways and phylogenetic relationships has also been covered. The development of CREMOFAC as a central repository for chromatin-remodeling factors and the absence of such a pre-existing database heighten its utility thus making its presence indispensable. AVAILABILITY: http://www.jncasr.ac.in/cremofac/

Animals↗

PubMed1988

Resin injection of thoracic paravertebral spaces.

Stained, quick setting resin was injected into the thoracic paravertebral spaces of six cadavers to assess the suitability of this material for delineating the spread of injected substances in an area of the human body which is being re-evaluated currently as a repository for analgesic drugs. The distribution and spread of the resin in relation to intercostal spaces, vertebral bodies and the spinal cord were noted, and compared with other studies.

Aged↗

PubMed1985

Improvements in glass capillary gas chromatographic polychlorobiphenyl analysis.

Separation of a 1:1:1:1 calibration mixture of Aroclors 1221, 1016, 1254, and 1260 on soda glass capillaries coated with Apolane (C-87) or Apiezon L is described. Polychlorobiphenyl congener structures are assigned to 112 separated and partially separated zones. The quantitative composition of Aroclor 1221 is reported. The performance of the two stationary phases on different lengths of laboratory and commercially prepared capillaries is compared and found to be very similar. Aroclors 1221, 1016, 1254, and 1260 are employed (1:1:1:1) for the primary calibration mixture because they contain all components of the commercial materials which pollute the environment; they are also easily obtained from the U.S. EPA Repository so that the method can be used in any laboratory by employing the calibration data given here.

Chromatography, Gas↗

PubMed1995

Xanthomonas maltophilia misidentified as Pseudomonas cepacia in cultures of sputum from patients with cystic fibrosis: a diagnostic pitfall with major clinical implications.

Pseudomonas cepacia infection in patients with cystic fibrosis (CF) has major significance in terms of infection control, psychosocial issues, and medical treatment. We describe three instances in which the diagnostic laboratory misidentified Xanthomonas maltophilia as P. cepacia in cultures of sputum from patients with CF. These errors were recognized when 3 (9%) of 32 isolates, which had all been identified as P. cepacia and had been submitted to the Canadian Pseudomonas Repository Laboratory (Vancouver, BC), were correctly identified there as X. maltophilia. Each of the three isolates grew well on P. cepacia media, turned a characteristic vivid pink color, were polymyxin-resistant, and were lysine-positive. All three were initially characterized incorrectly as oxidase-positive and DNase-negative. The diagnostic laboratory then reexamined 24 other isolates that had been identified as P. cepacia; complete biochemical testing confirmed that all were indeed P. cepacia. Because infection due to P. cepacia has major implications for patients with CF, when a possible strain of P. cepacia is isolated, careful and complete characterization should be performed.

Adult↗

PubMed1989

Expression and desensitisation of A2 purinoceptors on cultured bovine aortic endothelial cells.

Purine nucleotides and their metabolites are important mediators of vascular tone. Adenosine promotes relaxation of vascular smooth muscle, acting on the A2 subclass of purinoceptors. There is some evidence that these receptors are also present on vascular endothelial cells. We have therefore examined cultured aortic endothelial cells for adenosine (A2) sensitivity. Bovine aortic endothelial cells (AG4762) were obtained from the Institute of Aging cell repository (USA), and cultured in monolayer flasks. Adenylate cyclase activity in homogenates of AG4762 cells was increased by 5'-(N-ethylcarboxamido)-adenosine (NECA) greater than 2-chloroadenosine greater than adenosine. NECA dependent activation of adenylate cyclase was inhibited by 3-isobutyl-l-methylxanthine greater than theophylline greater than caffeine. The rank order of potency of these compounds identified the responses as mediated by A2 purinoceptors. Prolonged exposure of AG4762 cells to NECA in culture resulted in loss of A2 purinoceptor responsiveness, and purinoceptor activity could be restored to non-dividing densensitized cells by further culture in the absence of the desensitising agent. The cyclic AMP dependent phosphorylation of specific sites in endothelial cells may trigger a number of important biological events which are yet to be determined.

Adenosine↗

PubMed2002

Directional bias during mating type switching in Saccharomyces is independent of chromosomal architecture.

Haploid Saccharomyces cells have the remarkable potential to change mating type as often as every generation, a process accomplished by an intrachromosomal gene conversion between an expressor locus MAT and one of two repositories of mating type information, HML or HMR. The particular locus selected as donor is dictated by the mating type of the cell, a bias that ensures productive mating type interconversion. Here we use green fluorescent protein tagging of the expressor and donor loci on chromosome III to show that this preference for donor locus does not result from a predetermined organization of chromosome III: HML and MAT as well as HMR and MAT remain separated in cells of both mating types. In fact, cells in which the inappropriate donor locus is artificially tethered to MAT still predominantly select the correct donor. We find, though, that initiation of switching leads to a rapid association of the correct donor locus with MAT. Thus, in mating type switching in Saccharomyces, donor preference is imposed at commitment to recombination rather than at physical contact of interacting DNA strands.

Chromosomes, Fungal↗