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CEBS object model for systems biology data, SysBio-OM.

MOTIVATION: To promote a systems biology approach to understanding the biological effects of environmental stressors, the Chemical Effects in Biological Systems (CEBS) knowledge base is being developed to house data from multiple complex data streams in a systems friendly manner that will accommodate extensive querying from users. Unified data representation via a single object model will greatly aid in integrating data storage and management, and facilitate reuse of software to analyze and display data resulting from diverse differential expression or differential profile technologies. Data streams include, but are not limited to, gene expression analysis (transcriptomics), protein expression and protein-protein interaction analysis (proteomics) and changes in low molecular weight metabolite levels (metabolomics). RESULTS: To enable the integration of microarray gene expression, proteomics and metabolomics data in the CEBS system, we designed an object model, Systems Biology Object Model (SysBio-OM). The model is comprehensive and leverages other open source efforts, namely the MicroArray Gene Expression Object Model (MAGE-OM) and the Proteomics Experiment Data Repository (PEDRo) object model. SysBio-OM is designed by extending MAGE-OM to represent protein expression data elements (including those from PEDRo), protein-protein interaction and metabolomics data. SysBio-OM promotes the standardization of data representation and data quality by facilitating the capture of the minimum annotation required for an experiment. Such standardization refines the accuracy of data mining and interpretation. The open source SysBio-OM model, which can be implemented on varied computing platforms is presented here. AVAILABILITY: A universal modeling language depiction of the entire SysBio-OM is available at http://cebs.niehs.nih.gov/SysBioOM/. 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. The database and interface are being built to implement the model and will be available for public use at http://cebs.niehs.nih.gov.

Database Management Systems↗

Pedro: a configurable data entry tool for XML.

UNLABELLED: Pedro is a Java application that dynamically generates data entry forms for data models expressed in XML Schema, producing XML data files that validate against this schema. The software uses an intuitive tree-based navigation system, can supply context-sensitive help to users and features a sophisticated interface for populating data fields with terms from controlled vocabularies. The software also has the ability to import records from tab delimited text files and features various validation routines. AVAILABILITY: The application, source code, example models from several domains and tutorials can be downloaded from http://pedro.man.ac.uk/.

Computer Graphics↗

[Clinical laboratory system in a complete electronic hospital].

The use of a Laboratory Information System (LIS) and Laboratory Automation System (LAS) are clearly superior to manual results in terms of completeness and legibility. As the current clinical information system (CIS) in Gifu University Hospital consists of a complete electronic medical record system, the clinical laboratory was re-engineered to simplify workflow, pay attention to quality assurance, and decrease various costs by an intelligent laboratory management system. We named the new system Gifu Premiotic Intelligent Laboratory System (GPILS). Further advances will concentrate on the cost-effective use of LIS, and the potential use of GPILS in our laboratories will be discussed. In addition, because one of our clinical laboratories currently provides various useful clinical laboratory-oriented information to physicians and patients, we have developed new tools named the "Reference Data Base (RefDB)". In the near future, several different types of computer technology for various clinical laboratory information will lead to the development of highly specific platforms for LIS corresponding to a complete electronic medical record system.

Clinical Laboratory Information Systems↗

Using statistical and knowledge-based approaches for literature-based discovery.

The explosive growth in biomedical literature has made it difficult for researchers to keep up with advancements, even in their own narrow specializations. While researchers formulate new hypotheses to test, it is very important for them to identify connections to their work from other parts of the literature. However, the current volume of information has become a great barrier for this task and new automated tools are needed to help researchers identify new knowledge that bridges gaps across distinct sections of the literature. In this paper, we present a literature-based discovery system called LitLinker that incorporates knowledge-based methodologies with a statistical method to mine the biomedical literature for new, potentially causal connections between biomedical terms. We demonstrate LitLinker's ability to capture novel and interesting connections between diseases and chemicals, drugs, genes, or molecular sequences from the published biomedical literature. We also evaluate LitLinker's performance by using the information retrieval metrics of precision and recall.

Abstracting and Indexing↗

Exploring performance issues for a clinical database organized using an entity-attribute-value representation.

BACKGROUND: The entity-attribute-value representation with classes and relationships (EAV/CR) provides a flexible and simple database schema to store heterogeneous biomedical data. In certain circumstances, however, the EAV/CR model is known to retrieve data less efficiently than conventionally based database schemas. OBJECTIVE: To perform a pilot study that systematically quantifies performance differences for database queries directed at real-world microbiology data modeled with EAV/CR and conventional representations, and to explore the relative merits of different EAV/CR query implementation strategies. METHODS: Clinical microbiology data obtained over a ten-year period were stored using both database models. Query execution times were compared for four clinically oriented attribute-centered and entity-centered queries operating under varying conditions of database size and system memory. The performance characteristics of three different EAV/CR query strategies were also examined. RESULTS: Performance was similar for entity-centered queries in the two database models. Performance in the EAV/CR model was approximately three to five times less efficient than its conventional counterpart for attribute-centered queries. The differences in query efficiency became slightly greater as database size increased, although they were reduced with the addition of system memory. The authors found that EAV/CR queries formulated using multiple, simple SQL statements executed in batch were more efficient than single, large SQL statements. CONCLUSION: This paper describes a pilot project to explore issues in and compare query performance for EAV/CR and conventional database representations. Although attribute-centered queries were less efficient in the EAV/CR model, these inefficiencies may be addressable, at least in part, by the use of more powerful hardware or more memory, or both.

Database Management Systems↗

Review of clinical activity by microbiologists.

A data form was devised and used to collect information on clinical cases involving a microbiologist. From the results a relational database management system was created. Of a total of 280 interventions, 137 (49%) were proactive, and in 118 (86%) of these cases the advice given was accepted. The majority of the patients in these cases showed subsequent improvement. Of all the interventions, the given advice was acted upon in 235 (84%), in 22 (8%) it was not and for the remainder this information was not available. This study was a simple method of gaining information on the clinical involvement of the microbiology department of a large city hospital. It provides a reference point from which further research and audit can be based.

Databases, Factual↗

Establishing radiologic image transmission via a transmission control protocol/Internet protocol network between two teaching hospitals in Houston.

The technical and management considerations necessary for the establishment of a network link between computed tomography (CT) and magnetic resonance imaging (MRI) networks of two geographically separated teaching hospitals are presented. The University of Texas Medical School at Houston Department of Radiology provides radiology residency training at its primary teaching hospital and at a second county-run hospital located approximately 12 miles away. A direct network link between the two hospitals was desired to permit timely consultative services to residents and professional colleagues. The network link was established by integrating the county hospital free-standing imaging network into the network infrastructure of the Medical School and the main teaching hospital. Technical issues involved in the integration were reassignment of internet protocol (IP) addresses, determination of data transmission protocol compatibilities, proof of connectivity and image transmission, transmission speeds and network loading, and management of the new network. These issues were resolved in a planned stepwise fashion and despite the fact that the system has a rate-limiting T1 segment between the county hospital and the teaching hospital the transmission speed was deemed suitable. The project has proven successful and can provide a guide for planning similar projects elsewhere. It has in fact made possible several new services for the teaching and research activities of the department's faculty and residents, which were not envisaged before the implementation of this connection.

Computer Systems↗

Prototype implementation of the integrated genomic database.

We aim to develop an open software system to handle human genome data. The system, called Integrated Genomic Database (IGD), will integrate information from many genomic databases and experimental resources into a comprehensive target-end database (IGD TED). Users will access front-end client systems (IGD FRED) to download data of interest to their computers and merge them with their own local data. FREDs will provide persistent storage of, and instant access to, retrieved data; a friendly graphical interface; tools for querying, browsing, analyzing, and editing local data; interface to external analysis; and tools for communicating with the outside world. The TED will be accessible over the network (online and offline) as a read-only resource for multiple clients. It collects data from major databases for nucleotide and protein sequences and structures, genome maps, experimental reagents, phenotypes, and bibliographic data, and sets of raw data produced at genome centers and laboratories. Beside character-based access via Gopher, WAIS, FTP, and several query language interfaces to the TED, we will develop a specialized front-end client, IGD FRED, with its own database manager, based on the ACEDB program. The FRED will support graphical display methods for sequence feature maps, chromosomal genetic and physical maps, and experimental objects like clone grids, etc. FRED will also provide an interface to important analysis software packages and tools for submitting data to external databases in their own format.

Computer Communication Networks↗

The ASTRAL compendium for protein structure and sequence analysis.

The ASTRAL compendium provides several databases and tools to aid in the analysis of protein structures, particularly through the use of their sequences. The SPACI scores included in the system summarize the overall characteristics of a protein structure. A structural alignments database indicates residue equivalencies in superimposed protein domain structures. The PDB sequence-map files provide a linkage between the amino acid sequence of the molecule studied (SEQRES records in a database entry) and the sequence of the atoms experimentally observed in the structure (ATOM records). These maps are combined with information in the SCOPdatabase to provide sequences of protein domains. Selected subsets of the domain database, with varying degrees of similarity measured in several different ways, are also available. ASTRALmay be accessed at http://astral.stanford.edu/

Amino Acid Sequence↗

Radiological digital teaching file development: an overview.

Radiologists are collectors of interesting films for teaching purposes or for use in presentations and publications. Traditionally, hard copies of films have been stored in an organized fashion, usually in a filing cabinet or film library. This system has inherent limitations, such as the physical space required. Many of the shortcomings can be circumvented by development of an electronic teaching file. Whereas the implementation of an institutional radiological digital image database can require significant developmental effort and programming expertise, there are a number of web-based solutions which are freely available and can be relatively easily employed to establish a contemporary electronic image library. This article will review the various options and discuss the process of developing a digital image database.

Computer-Assisted Instruction↗

BioMOBY: an open source biological web services proposal.

BioMOBY is an Open Source research project which aims to generate an architecture for the discovery and distribution of biological data through web services; data and services are decentralised, but the availability of these resources, and the instructions for interacting with them, are registered in a central location called MOBY Central. BioMOBY adds to the web services paradigm, as exemplified by Universal Data Discovery and Integration (UDDI), by having an object-driven registry query system with object and service ontologies. This allows users to traverse expansive and disparate data sets where each possible next step is presented based on the data object currently in-hand. Moreover, a path from the current data object to a desired final data object could be automatically discovered using the registry. Native BioMOBY objects are lightweight XML, and make up both the query and the response of a simple object access protocol (SOAP) transaction.

Computer Communication Networks↗

Data pre-processing in liquid chromatography-mass spectrometry-based proteomics.

MOTIVATION: In a liquid chromatography-mass spectrometry (LC-MS)-based expressional proteomics, multiple samples from different groups are analyzed in parallel. It is necessary to develop a data mining system to perform peak quantification, peak alignment and data quality assurance. RESULTS: We have developed an algorithm for spectrum deconvolution. A two-step alignment algorithm is proposed for recognizing peaks generated by the same peptide but detected in different samples. The quality of LC-MS data is evaluated using statistical tests and alignment quality tests. AVAILABILITY: Xalign software is available upon request from the author.

Algorithms↗

Distributed data mining on grids: services, tools, and applications.

Data mining algorithms are widely used today for the analysis of large corporate and scientific datasets stored in databases and data archives. Industry, science, and commerce fields often need to analyze very large datasets maintained over geographically distributed sites by using the computational power of distributed and parallel systems. The grid can play a significant role in providing an effective computational support for distributed knowledge discovery applications. For the development of data mining applications on grids we designed a system called Knowledge Grid. This paper describes the Knowledge Grid framework and presents the toolset provided by the Knowledge Grid for implementing distributed knowledge discovery. The paper discusses how to design and implement data mining applications by using the Knowledge Grid tools starting from searching grid resources, composing software and data components, and executing the resulting data mining process on a grid. Some performance results are also discussed.

Algorithms↗

The HELIOS Medical Connection Services.

This paper presents the design and implementation of the HELIOS software component that deals with integration of medical applications in health information networks. The problem of interoperability between health information systems based on different data exchange syntaxes is first discussed. A meta-model, relying on CEN TC251 recommendations, is then presented as a possible solution to this problem and a message description language including these recommendations is proposed. Using this meta-model, the Medical Connection Services that comprises a generic message processing automaton, a resource manager and a mapper is able either to interpret messages expressed in a given syntax (e.g., EDIFACT, ASTM) and map them to the application objects or to automate the translation of the messages in another syntax. Special focus is given on the position of the Medical Connection Services within the HELIOS integration strategy (i.e., through data, presentation and communication). The problem of semantic heterogeneity is then discussed.

Computer Communication Networks↗

A graphical query generator for clinical research databases.

Clinical research involves recording, storage and retrieval of disease-related patient data, typically using a database system. In order to facilitate ad hoc queries to clinical databases we have developed a query generator with a graphical interface. The query generator uses an object-oriented data model which is visualized by directed graphs. The main focus of our work was the definition of object-oriented user views to the partly complex data structures of a relational database. Furthermore, we tried to define graphical abstractions for all common types of queries. Thus, even for non-expert database users such as clinicians, it is easy to assemble highly complex queries for a thorough examination of the content of large research databases.

Computer Graphics↗

CyDAS: a cytogenetic data analysis system.

For statistical analyses in cancer cytogenetics, the genomic changes encoded by the karyotype must be translated into numerical codes. We developed a program, which extracts chromosomal gains and losses as well as breakpoints from the karyotype. The changes are compiled in tables according to the chromosome bands involved and/or depicted in projection to the respective chromosome ideogram. The data are ready to be integrated into further statistical analyses. The program may be run as desktop or Internet application.

Chromosome Aberrations↗

Systems Biology Toolbox for MATLAB: a computational platform for research in systems biology.

We present a Systems Biology Toolbox for the widely used general purpose mathematical software MATLAB. The toolbox offers systems biologists an open and extensible environment, in which to explore ideas, prototype and share new algorithms, and build applications for the analysis and simulation of biological and biochemical systems. Additionally it is well suited for educational purposes. The toolbox supports the Systems Biology Markup Language (SBML) by providing an interface for import and export of SBML models. In this way the toolbox connects nicely to other SBML-enabled modelling packages. Models are represented in an internal model format and can be described either by entering ordinary differential equations or, more intuitively, by entering biochemical reaction equations. The toolbox contains a large number of analysis methods, such as deterministic and stochastic simulation, parameter estimation, network identification, parameter sensitivity analysis and bifurcation analysis.

Database Management Systems↗

Easing the transition between attribute-value databases and conventional databases for scientific data.

We have previously developed and described a modeling and development framework called EAV/CR, which is appropriate for designing databases containing highly heterogeneous and evolving data, as in the case of scientific databases for rapidly advancing domains. The use of EAV/CR has been hampered by the lack of generic tools for non-procedurally transferring data into or out of legacy systems or analytical packages: the transfer task is complicated by the different representation of EAV vs. conventional data, which is not addressed by commercial data-transfer programs. We have therefore created such a tool, which works with a wide variety of data sources that are accessible via Microsoft OLE DB technology. The data transfer tool requires minimal programmer intervention to set up, and no programming to use on a regular basis. Current limitations of the tool are also noted.

Database Management Systems↗