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The generic genome browser: a building block for a model organism system database.

The Generic Model Organism System Database Project (GMOD) seeks to develop reusable software components for model organism system databases. In this paper we describe the Generic Genome Browser (GBrowse), a Web-based application for displaying genomic annotations and other features. For the end user, features of the browser include the ability to scroll and zoom through arbitrary regions of a genome, to enter a region of the genome by searching for a landmark or performing a full text search of all features, and the ability to enable and disable tracks and change their relative order and appearance. The user can upload private annotations to view them in the context of the public ones, and publish those annotations to the community. For the data provider, features of the browser software include reliance on readily available open source components, simple installation, flexible configuration, and easy integration with other components of a model organism system Web site. GBrowse is freely available under an open source license. The software, its documentation, and support are available at http://www.gmod.org.

Animals↗

HCVDB: hepatitis C virus sequences database.

UNLABELLED: To date, more than 30 000 hepatitis C virus (HCV) sequences have been deposited in the generalist databases DNA Data Bank of Japan (DDBJ), EMBL Nucleotide Sequence Database (EMBL) and GenBank. The main difficulties with HCV sequences in these databases are their retrieval, annotation and analyses. To help HCV researchers face the increasing needs of HCV sequence analyses, we developed a specialised database of computer-annotated HCV sequences, called HCVDB. HCVDB is re-built every month from an up-to-date EMBL database by an automated process. HCVDB provides key data about the HCV sequences (e.g. genotype, genomic region, protein names and functions, known 3-dimensional structures) and ensures consistency of the annotations, which enables reliable keyword queries. The database is highly integrated with sequence and structure analysis tools and the SRS (LION bioscience) keywords query system. Thus, any user can extract subsets of sequences matching particular criteria or enter their own sequences and analyse them with various bioinformatics programs available on the same server. AVAILABILITY: HCVDB is available from http://hepatitis.ibcp.fr.

Amino Acid Sequence↗

Computerizing incident reporting at a community hospital.

BACKGROUND: A community hospital in Seattle, Northwest Hospital (NWH), reengineered its paper-based incident reporting system into a computerized reporting, notification, and tracking tool. In July 1996 a small interdisciplinary working group was formed to improve the incident reporting system so that it would decrease the time needed to complete an incident report, collect more precise data about the incident, allow department managers instant access to all open memos involving or generated by their departments, allow ad hoc reporting by managers and administration, and allow only involved parties access to memos. IMPLEMENTATION AND EVALUATION: After a pilot study was conducted in the Childbirth Center and the pharmacy department began using the computerized incident reporting system, other units began using the system according to a weekly roll-out schedule during the first two quarters of 1998. In the third quarter of 1998, NWH began using the system as its primary quality assurance and incident reporting tool. As soon as an incident is documented, it is in the database and available for reporting. Data collected from January 1998 through December 1999 indicated that turnaround time for the life cycle of an incident report decreased from 53 to 12 days. At least 20 hours a month were saved in transcription and data entry time using the new system. DISCUSSION: Although incident reporting is now more streamlined and efficient, a few issues have emerged that need to be addressed, some relating to users' incorrect entering of information. Improvements are still being made to the system on an ongoing basis.

Accidental Falls↗

ORegAnno: an open access database and curation system for literature-derived promoters, transcription factor binding sites and regulatory variation.

MOTIVATION: Our understanding of gene regulation is currently limited by our ability to collectively synthesize and catalogue transcriptional regulatory elements stored in scientific literature. Over the past decade, this task has become increasingly challenging as the accrual of biologically validated regulatory sequences has accelerated. To meet this challenge, novel community-based approaches to regulatory element annotation are required. SUMMARY: Here, we present the Open Regulatory Annotation (ORegAnno) database as a dynamic collection of literature-curated regulatory regions, transcription factor binding sites and regulatory mutations (polymorphisms and haplotypes). ORegAnno has been designed to manage the submission, indexing and validation of new annotations from users worldwide. Submissions to ORegAnno are immediately cross-referenced to EnsEMBL, dbSNP, Entrez Gene, the NCBI Taxonomy database and PubMed, where appropriate. AVAILABILITY: ORegAnno is available directly through MySQL, Web services, and online at http://www.oreganno.org. All software is licensed under the Lesser GNU Public License (LGPL).

Binding Sites↗

Annotating PDB files with scene information.

We have implemented extensions to the Brookhaven Protein Data Bank (PDB) file format for incorporating scene information such as viewing parameters, additional molecular information (e.g., van der Waals radii and atom colors), and user-defined graphics. These extensions were made in conformance with the PDB standard and provide sufficient information to render the scene in various styles such as space-filling images and ribbon diagrams. For the past 5 years these extensions have been used in the MidasPlus molecular modeling system and have proved both powerful and sufficient for generating complex molecular images. We propose that the extensions to the PDB presented here be adopted by the molecular modeling community for incorporation into visualization programs.

Computer Graphics↗

Navigator: tools for informal structure-activity relationship discovery.

Navigator is a molecular database visualization system, designed to support exploratory data analysis and informal structure-activity relationship studies. In addition to the operations commonly found in chemical database systems, it provides new tools that facilitate substituent analysis and help elucidate the relationships among similar molecules and between related assays. Navigator's capabilities include two ways of displaying the relationships between analogs, mouse-sensitive charts of sets of molecules, mouse-sensitive plots of assay relationships, and access to a system for three-dimensional quantitative structure-activity relationship discovery. Navigator's mouse-based user interface provides a one-object/one-window paradigm that makes data manipulation easy even for inexperienced users. Navigator runs on Silicon Graphics workstations.

Computer Graphics↗

The interaction of domain knowledge and linguistic structure in natural language processing: interpreting hypernymic propositions in biomedical text.

Interpretation of semantic propositions in free-text documents such as MEDLINE citations would provide valuable support for biomedical applications, and several approaches to semantic interpretation are being pursued in the biomedical informatics community. In this paper, we describe a methodology for interpreting linguistic structures that encode hypernymic propositions, in which a more specific concept is in a taxonomic relationship with a more general concept. In order to effectively process these constructions, we exploit underspecified syntactic analysis and structured domain knowledge from the Unified Medical Language System (UMLS). After introducing the syntactic processing on which our system depends, we focus on the UMLS knowledge that supports interpretation of hypernymic propositions. We first use semantic groups from the Semantic Network to ensure that the two concepts involved are compatible; hierarchical information in the Metathesaurus then determines which concept is more general and which more specific. A preliminary evaluation of a sample based on the semantic group Chemicals and Drugs provides 83% precision. An error analysis was conducted and potential solutions to the problems encountered are presented. The research discussed here serves as a paradigm for investigating the interaction between domain knowledge and linguistic structure in natural language processing, and could also make a contribution to research on automatic processing of discourse structure. Additional implications of the system we present include its integration in advanced semantic interpretation processors for biomedical text and its use for information extraction in specific domains. The approach has the potential to support a range of applications, including information retrieval and ontology engineering.

Abstracting and Indexing↗

A framework for analyzing the cognitive complexity of computer-assisted clinical ordering.

Computer-assisted provider order entry is a technology that is designed to expedite medical ordering and to reduce the frequency of preventable errors. This paper presents a multifaceted cognitive methodology for the characterization of cognitive demands of a medical information system. Our investigation was informed by the distributed resources (DR) model, a novel approach designed to describe the dimensions of user interfaces that introduce unnecessary cognitive complexity. This method evaluates the relative distribution of external (system) and internal (user) representations embodied in system interaction. We conducted an expert walkthrough evaluation of a commercial order entry system, followed by a simulated clinical ordering task performed by seven clinicians. The DR model was employed to explain variation in user performance and to characterize the relationship of resource distribution and ordering errors. The analysis revealed that the configuration of resources in this ordering application placed unnecessarily heavy cognitive demands on the user, especially on those who lacked a robust conceptual model of the system. The resources model also provided some insight into clinicians' interactive strategies and patterns of associated errors. Implications for user training and interface design based on the principles of human-computer interaction in the medical domain are discussed.

Cognition↗

MeKE: discovering the functions of gene products from biomedical literature via sentence alignment.

MOTIVATION: Research on roles of gene products in cells is accumulating and changing rapidly, but most of the results are still reported in text form and are not directly accessible by computers. To expedite the progress of functional bioinformatics, it is, therefore, important to efficiently process large amounts of biomedical literature and transform the knowledge extracted into a structured format usable by biologists and medical researchers. Our aim was to develop an intelligent text-mining system that will extract from biomedical documents knowledge about the functions of gene products and thus facilitate computing with function. RESULTS: We have developed an ontology-based text-mining system to efficiently extract from biomedical literature knowledge about the functions of gene products. We also propose methods of sentence alignment and sentence classification to discover the functions of gene products discussed in digital texts. AVAILABILITY: http://ismp.csie.ncku.edu.tw/~yuhc/meke/

Biomedical Research↗

Pathfinder: multiresolution region-based searching of pathology images using IRM.

The fast growth of digitized pathology slides has created great challenges in research on image database retrieval. The prevalent retrieval technique involves human-supplied text annotations to describe slide contents. These pathology images typically have very high resolution, making it difficult to search based on image content. In this paper, we present Pathfinder, an efficient multiresolution region-based searching system for high-resolution pathology image libraries. The system uses wavelets and the IRM (Integrated Region Matching) distance. Experiments with a database of 70,000 pathology image fragments have demonstrated high retrieval accuracy and high speed. The algorithm can be combined with our previously developed wavelet-based progressive pathology image transmission and browsing algorithm and is expandable for medical image databases.

Abstracting and Indexing↗

MUTAGEN: multi-user tool for annotating genomes.

SUMMARY: MUTAGEN is a free prokaryotic annotation system. It offers the advantages of genome comparison, graphical sequence browsers, search facilities and open-source for user-specific adjustments. The web-interface allows several users to access the system from standard desktop computers. The Sulfolobus acidocaldarius genome, and several plasmids and viruses have so far been analysed and annotated using MUTAGEN. AVAILABILITY: MUTAGEN is released as open-source software under GPL. The code is available for download and/or contribution at http://dac.molbio.ku.dk/bioinformatics/MUTAGEN/

Database Management Systems↗

Omic space: coordinate-based integration and analysis of genomic phenomic interactions.

MOTIVATION: With the recent progress in genomics, various data sets of omic interactions describing networks of omic elements have become available. In order to obtain reliable hypotheses from the data, it is effective to integrate interactions from different sorts of data sets. In order to facilitate a coordinate-based integration and analysis of omic interactions, we introduce the concept of an omic space comprising a comprehensive set of omic planes. Genomic, transcriptomic, proteomic, metabolomic, phenomic and other omic planes are defined by two orthogonal genomic-coordinate axes. RESULTS: We show that the omic space concept helps us to assimilate biological findings comprehensively into hypotheses or models combining higher-order phenomena and lower-order mechanisms by demonstrating that a comprehensive ranking of correspondences among interactions in the space can be used effectively for estimating candidates of responsible gene pairs for epistatic interacting loci of tumors in mice. We also show that the omic space offers a convenient framework for database integration, by presenting a system named the 'Genome <==> Phenome Superhighway' (GPS) that serves as a framework for integration and visualization of omic interactions based on omic spaces of some model species including Homo sapiens, Mus musculus, Caenorhabditis elegans and Arabidopsis thaliana. AVAILABILITY: For the GPS web site, see http://omicspace.riken.jp/gps/.

Algorithms↗

Provenance and annotation for visual exploration systems.

Exploring data using visualization systems has been shown to be an extremely powerful technique. However, one of the challenges with such systems is an inability to completely support the knowledge discovery process. More than simply looking at data, users will make a semipermanent record of their visualizations by printing out a hard copy. Subsequently, users will mark and annotate these static representations, either for dissemination purposes or to augment their personal memory of what was witnessed. In this paper, we present a model for recording the history of user explorations in visualization environments, augmented with the capability for users to annotate their explorations. A prototype system is used to demonstrate how this provenance information can be recalled and shared. The prototype system generates interactive visualizations of the provenance data using a spatio-temporal technique. Beyond the technical details of our model and prototype, results from a controlled experiment that explores how different history mechanisms impact problem solving in visualization environments are presented.

Algorithms↗

LabPatch, an acquisition and analysis program for patch-clamp electrophysiology.

An acquisition and analysis program, "LabPatch," has been developed for use in patch-clamp research. LabPatch controls any patch-clamp amplifier, acquires and records data, runs voltage protocols, plots and analyzes data, and connects to spreadsheet and database programs. Controls within LabPatch are grouped by function on one screen, much like an oscilloscope front panel. The software is mouse driven, so that the user need only point and click. Finally, the ability to copy data to other programs running in Windows 95/98, and the ability to keep track of experiments using a database, make LabPatch extremely versatile. The system requirements include Windows 95/98, at least a 100-MHz processor and 16 MB RAM, a data acquisition card, digital-to-analog converter, and a patch-clamp amplifier. LabPatch is available free of charge at http://www.fhs.mcmaster.ca/huizinga/.

Computer Graphics↗

Establishing a reliable visual function test and applying it to screening optic nerve disease in onchocercal communities.

The computer Controlled Video Perimetry (CCVP) is a computer screening test for detecting visual function loss caused by onchocerciasis, glaucoma, etc. Installed on portable computers, the CCVP has been shown to be high acceptability in field community investigation. However, it is regarded to be difficult in obtaining reliable results from portable computer screening tests because of human behavioural variants and the lack of standard testing environment. In this paper, we propose an architecture for implementing a more reliable CCVP system. In particular, a self-organising neural network is applied to manage measurement noise caused by behavioural factors. A control unit is introduced to manage the overall behaviour of the system. The integrated test system has been used to screen optic nerve disease in onchocercal communities of rural Nigeria and the experimental results obtained from a large number of test records are very encouraging: reliable results from volatile test environments may be obtained using the proposed method.

Artifacts↗

A relational database application in support of integrated neuroscience research.

The development of relational databases has significantly improved the performance of storage, search, and retrieval functions and has made it possible for applications that perform real-time data acquisition and analysis to interact with these types of databases. The purpose of this research was to develop a user interface for interaction between a data acquisition and analysis application and a relational database using the Oracle9i system. The overall system was designed to have an indexing capability that threads into the data acquisition and analysis programs. Tables were designed and relations within the database for indexing the files and information contained within the files were established. The system provides retrieval capabilities over a broad range of media, including analog, event, and video data types. The system's ability to interact with a data capturing program at the time of the experiment to create both multimedia files as well as the meta-data entries in the relational database avoids manual entries in the database and ensures data integrity and completeness for further interaction with the data by analysis applications.

Database Management Systems↗

InterProScan--an integration platform for the signature-recognition methods in InterPro.

UNLABELLED: InterProScan is a tool that scans given protein sequences against the protein signatures of the InterPro member databases, currently--PROSITE, PRINTS, Pfam, ProDom and SMART. The number of signature databases and their associated scanning tools as well as the further refinement procedures make the problem complex. InterProScan is designed to be a scalable and extensible system with a robust internal architecture. AVAILABILITY: The Perl-based InterProScan implementation is available from the EBI ftp server (ftp://ftp.ebi.ac.uk/pub/software/unix/iprscan/) and the SRS-basedInterProScan is available upon request. We provide the public web interface (http://www.ebi.ac.uk/interpro/scan.html) as well as email submission server (interproscan@ebi.ac.uk).

Database Management Systems↗

THEA: ontology-driven analysis of microarray data.

MOTIVATION: Microarray technology makes it possible to measure thousands of variables and to compare their values under hundreds of conditions. Once microarray data are quantified, normalized and classified, the analysis phase is essentially a manual and subjective task based on visual inspection of classes in the light of the vast amount of information available. Currently, data interpretation clearly constitutes the bottleneck of such analyses and there is an obvious need for tools able to fill the gap between data processed with mathematical methods and existing biological knowledge. RESULTS: THEA (Tools for High-throughput Experiments Analysis) is an integrated information processing system allowing convenient handling of data. It allows to automatically annotate data issued from classification systems with selected biological information coming from a knowledge base and to either manually search and browse through these annotations or automatically generate meaningful generalizations according to statistical criteria (data mining). AVAILABILITY: The software is available on the website http://thea.unice.fr/

Abstracting and Indexing↗