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The genome data base (GDB)--a human gene mapping repository.

The types of gene mapping data and its organization in the Genome Data Base (GDB) recently established at Johns Hopkins Medical School are described. The database provides a continuous online environment for data perusal and editing and is used as the informatics core for running the human gene mapping workshops. Current development is primarily concentrated on extending the types of map object, means of defining map location, map storage and representation. Experimental data structures have been created that permit storage of any type of map information, physical or genetic.

Baltimore↗

A practical approach to public health surveillance of violent deaths related to intimate partner relationships.

OBJECTIVES: Articles describing the epidemiology of intimate partner homicide (IPH) have often been positioned as one-time research projects utilizing a single data source for case identification. However, researchers without access to centralized repositories for data pertinent to IPH can ascertain cases by using multiple extant data sources. The authors describe a surveillance system that can serve as a model for state health departments and others seeking to quantify and characterize violent deaths related to intimate partner relationships on an ongoing basis. METHODS: Retrospective surveillance was conducted to identify and characterize deaths related to intimate partnerships by linking the following data sources: death certificates, newspaper articles, law enforcement reports, and medical examiners' records. RESULTS: The authors identified at least 34% more IPHs using multiple data sources than would have been recognized solely using Supplementary Homicide Reports--the most frequently cited data source for IPH case ascertainment--and 22% more cases than newspaper data alone would have allowed for. CONCLUSIONS: While it was discovered that at least 181 IPHs--and at least 128 other deaths related to intimate partnerships--occurred in Michigan from 1999-2001, this frequency of occurrences is probably conservative. This limitation is due, in part, to the researchers not having access to information from all possible data source contributors. However, in the absence of statewide data systems, the authors demonstrate the utility of using multiple data sources for violent death surveillance to address incomplete case ascertainment.

Female↗

Managing medical research data with a Web-Interfacing Repository Manager.

This paper describes the Web-Interfacing Repository Manager (WIRM), a perl toolkit for managing and deploying multimedia data, which is built entirely from free, platform-independent components. The WIRM consists of an object-relational API layered over a relational database, with built-in support for file management and CGI programming. The basic underlying data structure for all WIRM data is the repository object, a perl associative array whose values are bound to a row of a table in the relational database. Based on our experience implementing a target application (the Brain Mapper Console), we describe five stages through which a system passes as it evolves from a primitive file hierarchy to a full-fledged repository console.

Brain Mapping↗

Clustering methods for analyzing large data sets: gonad development, a study case.

With the development of data set repositories, it is now possible to collate high numbers of related results by gathering data from experiments carried out in different laboratories and addressing similar questions or using a single type of biological material under different conditions. To address the challenge posed by the heterogeneous nature of multiple data sources, this chapter presents several methods used routinely for assessing the quality of data (i.e., reproducibility of replicates and similarity between experimental points obtained under identical or similar biological conditions). As gene clustering on large data sets is not straightforward, this chapter also presents a rapid gene clustering method that involves translating variation profiles from an ordered set of comparisons into chains of symbols. In addition, it shows that lists of genes assembled based on the presence of a common term in their functional description can be used to find the most informative comparisons and to construct from them exemplar chains of symbols that are useful for clustering similar genes. Finally, this symbolic approach is extended to the overall set of biological conditions under study and shows how the resultant collection of variation profiles can be used to construct transcriptional networks, which in turn can be used as powerful tools for gene clustering.

Animals↗

Medical image informatics infrastructure design and applications.

Picture archiving and communication systems (PACS) is a system integration of multimodality images and health information systems designed for improving the operation of a radiology department. As it evolves, PACS becomes a hospital image document management system with a voluminous image and related data file repository. A medical image informatics infrastructure can be designed to take advantage of existing data, providing PACS with add-on value for health care service, research, and education. A medical image informatics infrastructure (MIII) consists of the following components: medical images and associated data (including PACS database), image processing, data/knowledge base management, visualization, graphic user interface, communication networking, and application oriented software. This paper describes these components and their logical connection, and illustrates some applications based on the concept of the MIII.

Age Determination by Skeleton↗

Strategies for comparing gene expression profiles from different microarray platforms: application to a case-control experiment.

Meta-analysis of microarray data is increasingly important, considering both the availability of multiple platforms using disparate technologies and the accumulation in public repositories of data sets from different laboratories. We addressed the issue of comparing gene expression profiles from two microarray platforms by devising a standardized investigative strategy. We tested this procedure by studying MDA-MB-231 cells, which undergo apoptosis on treatment with resveratrol. Gene expression profiles were obtained using high-density, short-oligonucleotide, single-color microarray platforms: GeneChip (Affymetrix) and CodeLink (Amersham). Interplatform analyses were carried out on 8414 common transcripts represented on both platforms, as identified by LocusLink ID, representing 70.8% and 88.6% of annotated GeneChip and CodeLink features, respectively. We identified 105 differentially expressed genes (DEGs) on CodeLink and 42 DEGs on GeneChip. Among them, only 9 DEGs were commonly identified by both platforms. Multiple analyses (BLAST alignment of probes with target sequences, gene ontology, literature mining, and quantitative real-time PCR) permitted us to investigate the factors contributing to the generation of platform-dependent results in single-color microarray experiments. An effective approach to cross-platform comparison involves microarrays of similar technologies, samples prepared by identical methods, and a standardized battery of bioinformatic and statistical analyses.

Breast Neoplasms↗

Database development in toxicogenomics: issues and efforts.

The marriage of toxicology and genomics has created not only opportunities but also novel informatics challenges. As with the larger field of gene expression analysis, toxicogenomics faces the problems of probe annotation and data comparison across different array platforms. Toxicogenomics studies are generally built on standard toxicology studies generating biological end point data, and as such, one goal of toxicogenomics is to detect relationships between changes in gene expression and in those biological parameters. These challenges are best addressed through data collection into a well-designed toxicogenomics database. A successful publicly accessible toxicogenomics database will serve as a repository for data sharing and as a resource for analysis, data mining, and discussion. It will offer a vehicle for harmonizing nomenclature and analytical approaches and serve as a reference for regulatory organizations to evaluate toxicogenomics data submitted as part of registrations. Such a database would capture the experimental context of in vivo studies with great fidelity such that the dynamics of the dose response could be probed statistically with confidence. This review presents the collaborative efforts between the European Molecular Biology Laboratory-European Bioinformatics Institute ArrayExpress, the International Life Sciences Institute Health and Environmental Science Institute, and the National Institute of Environmental Health Sciences National Center for Toxigenomics Chemical Effects in Biological Systems knowledge base. The goal of this collaboration is to establish public infrastructure on an international scale and examine other developments aimed at establishing toxicogenomics databases. In this review we discuss several issues common to such databases: the requirement for identifying minimal descriptors to represent the experiment, the demand for standardizing data storage and exchange formats, the challenge of creating standardized nomenclature and ontologies to describe biological data, the technical problems involved in data upload, the necessity of defining parameters that assess and record data quality, and the development of standardized analytical approaches.

Animals↗

Common data element (CDE) management and deployment in clinical trials.

The NCI provides the cancer Data Standards Repository (caDSR) to support development and deployment of CDEs in cancer research. The caDSR, part of the NCI caCORE infrastructure, supports data management workflow requirements and adherence to ISO/IEC 11179 metadata standards. CDEs are developed using standard terminology from caCORE vocabulary services, and are then deployed to multi-site clinical trials data management systems. Here we describe the caDSR and how CDEs are managed and deployed in clinical research.

Biomedical Research↗

Stage of change for making an informed decision about Medicare health plans.

OBJECTIVE: To assess the applicability of the transtheoretical model of change (TTM) to informed choice in the Medicare population. DATA SOURCES/STUDY SETTING: Two hundred and thirty-nine new Medicare enrollees randomly selected from the Center for Medicare and Medicaid Services' October 2001 Initial Enrollee File, a repository of data for persons who are going to turn 65 and become entitled to enroll in Medicare in the next 3 months. STUDY DESIGN: Study participants completed TTM measures of stage of change, decisional balance, and self-efficacy for informed choice, as well as measures of Medicare knowledge, perceived knowledge, and information seeking. Model testing was conducted to determine whether well-established relationships between stage of change, decisional balance, and self-efficacy replicate for informed choice in the Medicare population, and whether Medicare knowledge and information-seeking increase across the stages. DATA COLLECTION/EXTRACTION METHODS: Survey data were collected using mail surveys with telephone follow-up for nonresponders. PRINCIPAL FINDINGS: Predicted relationships were established between stage of change for informed choice and decisional balance, self-efficacy, Medicare knowledge, and information seeking. The amount of variance accounted for by stage of change for informed choice was larger than that found for smoking cessation, where the TTM has had its greatest successes. CONCLUSIONS: The methods and findings lay the groundwork for development of TTM-based interventions for Medicare beneficiaries, and provide a prototype for the application of the TTM to informed decision making among other types of consumers who are being asked to take more responsibility for their health care.

Female↗

CryptoDB: the Cryptosporidium genome resource.

CryptoDB (http://CryptoDB.org) represents a collaborative effort to locate all genome data for the apicomplexan parasite Cryptosporidium parvum in a single user-friendly database. CryptoDB currently houses the genomic sequence data for both the human type 1 H strain and the bovine type 2 IOWA strain in addition to all other available EST and GSS sequences obtained from public repositories. All data are available for data mining via BLAST, keyword searches of pre-computed BLASTX results and user-defined or PROSITE motif pattern searches. Release 1.0 of CryptoDB contains approximately 19 million bases of genome sequence for the H and IOWA strains and an additional approximately 24 million bases of GSS and EST sequence obtained from other sources. Open reading frames greater than 50 and 100 amino acids have been generated for all sequences and all data are available for bulk download. This database, like other apicomplexan parasite databases, has been built utilizing the PlasmoDB model.

Animals↗

Effective drug-allergy checking: methodological and operational issues.

Adverse drug events cause a large number of injuries, and adverse events caused by medications administered in the face of known allergies represent an important preventable cause of patient harm. Computerized systems can effectively prevent reactions due to known allergies, but building an effective allergy prevention feature is challenging and presents many interesting informatics issues that have both methodological and operational implications. In this paper, we present the experiences from one large delivery system in delivering allergy-related decision support, discuss some of the different approaches that we have used, and then propose a future approach. We also discuss the methodological, behavioral, and operational issues that have arisen which have a major impact on success. Key factors in drug-allergy checking include storing patient allergy data in a single common repository, representing allergy data using suitable terminologies and creating groups of allergies for inferencing purposes, being judicious about which allergy warnings to display, conveying the reaction that the patient has experienced when exposed to the drug to inform the provider of the importance of the warning, and perhaps most important, implementing strategies to optimize the likelihood that allergy information will be entered.

Database Management Systems↗

The PeptideAtlas project.

The completion of the sequencing of the human genome and the concurrent, rapid development of high-throughput proteomic methods have resulted in an increasing need for automated approaches to archive proteomic data in a repository that enables the exchange of data among researchers and also accurate integration with genomic data. PeptideAtlas (http://www.peptideatlas.org/) addresses these needs by identifying peptides by tandem mass spectrometry (MS/MS), statistically validating those identifications and then mapping identified sequences to the genomes of eukaryotic organisms. A meaningful comparison of data across different experiments generated by different groups using different types of instruments is enabled by the implementation of a uniform analytic process. This uniform statistical validation ensures a consistent and high-quality set of peptide and protein identifications. The raw data from many diverse proteomic experiments are made available in the associated PeptideAtlas repository in several formats. Here we present a summary of our process and details about the Human, Drosophila and Yeast PeptideAtlas builds.

Animals↗

TMA-Combiner, a simple software tool to permit analysis of replicate cores on tissue microarrays.

We have previously published a suite of software tools that facilitates the reformulation of tissue microarray (TMA) data so that it may be analyzed using techniques originally devised for analysis of cDNA microarray data. However, current microarray data often feature multiple scores for a given tissue sample and antibody combination. Furthermore, an efficient and systematic method for combining scores that takes into account the differing staining properties of tissue epitopes has not been described. We thus present the TMA-Combiner, a new Microsoft Excel-based macro that permits analysis of data for which tissues may have two or more scores per antibody, and permits combination of data from multiple different tissue microarrays. It accomplishes this by rendering one score per tissue per antibody from two or more scores, using one of multiple user-selectable combination rules developed to account for the differing staining properties of tissue epitopes. This greatly facilitates analysis of tissue microarrays, particularly for users with large repositories of data, and may facilitate discovery of biological trends and help refine diagnostic accuracy of tissue markers in clinical samples.

Cluster Analysis↗

The caCORE Software Development Kit: streamlining construction of interoperable biomedical information services.

BACKGROUND: Robust, programmatically accessible biomedical information services that syntactically and semantically interoperate with other resources are challenging to construct. Such systems require the adoption of common information models, data representations and terminology standards as well as documented application programming interfaces (APIs). The National Cancer Institute (NCI) developed the cancer common ontologic representation environment (caCORE) to provide the infrastructure necessary to achieve interoperability across the systems it develops or sponsors. The caCORE Software Development Kit (SDK) was designed to provide developers both within and outside the NCI with the tools needed to construct such interoperable software systems. RESULTS: The caCORE SDK requires a Unified Modeling Language (UML) tool to begin the development workflow with the construction of a domain information model in the form of a UML Class Diagram. Models are annotated with concepts and definitions from a description logic terminology source using the Semantic Connector component. The annotated model is registered in the Cancer Data Standards Repository (caDSR) using the UML Loader component. System software is automatically generated using the Codegen component, which produces middleware that runs on an application server. The caCORE SDK was initially tested and validated using a seven-class UML model, and has been used to generate the caCORE production system, which includes models with dozens of classes. The deployed system supports access through object-oriented APIs with consistent syntax for retrieval of any type of data object across all classes in the original UML model. The caCORE SDK is currently being used by several development teams, including by participants in the cancer biomedical informatics grid (caBIG) program, to create compatible data services. caBIG compatibility standards are based upon caCORE resources, and thus the caCORE SDK has emerged as a key enabling technology for caBIG. CONCLUSION: The caCORE SDK substantially lowers the barrier to implementing systems that are syntactically and semantically interoperable by providing workflow and automation tools that standardize and expedite modeling, development, and deployment. It has gained acceptance among developers in the caBIG program, and is expected to provide a common mechanism for creating data service nodes on the data grid that is under development.

Humans↗

Mining protein data from two-dimensional gels: tools for systematic post-planned analyses.

There is a considerable need to develop comprehensive, systematic mechanisms to analyze the vast number of proteins that orchestrate various cellular functions and to identify proteins associated with disease or that are affected by pharmacological agents. Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) continues to be relied upon to analyze protein constituents of cells and tissues. We have developed a Laboratory Information Processing System (LIPS) as a computer-based tool for capturing quantitative and qualitative changes in thousands of proteins detected in 2-D gels of various types. Protein databases have been developed to serve as a repository for data processing of the basic and derived data and of findings derived from different studies. There have been remarkable advances both in database technology as well as in the computer hardware that have benefited our effort at mining protein data from 2-D gels. We here review our current efforts aimed at improving the performance and features of our 2-D related protein databases, with particular emphasis on the tools we utilize for database mining via a systematic analysis of information known as post-planned analysis.

Acrylic Resins↗

The assessment of biomarkers to detect nephrotoxicity using an integrated database.

Groups of industrial workers exposed to heavy metals (cadmium, mercury, and lead) or solvents were studied together with corresponding control groups. The cohorts were collected from several European centers (countries). Eighty-one measurements were carried out on urine, blood, and serum samples and the results of these analyses together with questionnaire information on each individual were entered into a central database using the relational database package Rbase. After the completion of the database construction phase, the data were exported in a format suitable for analysis by the statistical package SAS. The potential value of each test as an indicator of nephrotoxicity was then assessed. Rigorous exclusion criteria were applied which resulted in the elimination of some tests and samples from the dataset. The measurable contributions of smoking, gender, metal exposure, and site were either singly or in combination assessed by biomarkers for nephrotoxicity. The parameters measured included three urinary enzymes, six specific proteins, total protein, two extracellular matrix markers, four prostaglandins and anti-GBM antibodies, and beta 2-microglobulin in serum. The most sensitive renal tests included the urinary enzymes N-acetyl-beta-D-glucosaminidase (NAG) and intestinal alkaline phosphatase (IAP), brush border antigens, and urinary low-molecular-weight proteins. Of the newer tests investigated the prostaglandins were the most promising. Different patterns of biomarker excretion were observed following exposure to lead, cadmium, or mercury. The dataset provides a unique repository of data which could provide the basis of an enlarging source of information on normal human reference ranges and on the effects of exposure to toxins and the use of biomarkers for monitoring nephrotoxicity.

Biomarkers↗

Pivoting approaches for bulk extraction of Entity-Attribute-Value data.

Entity-Attribute-Value (EAV) data, as present in repositories of clinical patient data, must be transformed (pivoted) into one-column-per-parameter format before it can be used by a variety of analytical programs. Pivoting approaches have not been described in depth in the literature, and existing descriptions are dated. We describe and benchmark three alternative algorithms to perform pivoting of clinical data in the context of a clinical study data management system. We conclude that when the number of attributes to be returned is not too large, it is feasible to use static SQL as the basis for views on the data. An alternative but more complex approach that utilizes hash tables and the presence of abundant random-access-memory can achieve improved performance by reducing the load on the database server.

Algorithms↗