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PubMed1985

Diagnostic library support system for medical practice.

Here is a tragic case where the diagnosis was missed on three separate occasions over a 19-month period. Both terminal conditions are treatable and potentially separable if discovered and aggressively managed. It is not the intent of this presentation to criticize the evaluation of this patient, but rather to point out the need and, also, the potential benefits of an alternate approach, which could have significantly changed the course of this particular patient's evaluation. We have conducted similar analyses with other CPC cases with almost equivalent specificity. These same evaluations have been performed in a real clinical setting with live patient data. What we have learned so far we think will be extremely helpful in extending the potential application of this technology: A text-based decision support tool is only as good as its practitioner. It takes practice and training to learn to use this system effectively. There are many traps in logic, and the use of words and terms within the text must be understood to effectively utilize this tool. There are shortcuts in logical analysis which we mentally use all the time but which cannot be accepted using this system (e.g., you must not rely on your memory or any specific associations to circumvent the system). The system will only become clinically relevant when the entire field of medicine is included in the data base. This is one of our current limitations with only two-thirds of the Merck medical text available for reference. This makes it difficult to apply to a general medical problem since we are not sure which direction the case might take, and often these are multisystem diseases or problems that put us at a severe disadvantage if we don't have the necessary data base. The structure and integrity of the data base are critical to the success of the system. Since numbers are ubiquitous, these cannot be used for key word elements. Techniques must be introduced to create word-oriented numbers that can be uniquely identified (e.g., "AGE14-20"). The publisher of the data must supply a continuous flow of up-to-date material that can be incorporated within the framework of the working system. It is possible to train medical technicians to use the system if they are familiar with medical terminology. The speed and, perhaps, the precision of their analysis could not be expected to rival that of a medical specialist.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed2006

Combining multi-species genomic data for microRNA identification using a Naive Bayes classifier.

MOTIVATION: Most computational methodologies for microRNA gene prediction utilize techniques based on sequence conservation and/or structural similarity. In this study we describe a new technique, which is applicable across several species, for predicting miRNA genes. This technique is based on machine learning, using the Naive Bayes classifier. It automatically generates a model from the training data, which consists of sequence and structure information of known miRNAs from a variety of species. RESULTS: Our study shows that the application of machine learning techniques, along with the integration of data from multiple species is a useful and general approach for miRNA gene prediction. Based on our experiments, we believe that this new technique is applicable to an extensive range of eukaryotes' genomes. Specific structure and sequence features are first used to identify miRNAs followed by a comparative analysis to decrease the number of false positives (FPs). The resulting algorithm exhibits higher specificity and similar sensitivity compared to currently used algorithms that rely on conserved genomic regions to decrease the rate of FPs.

Algorithms↗

PubMed2004

EnsMart: a generic system for fast and flexible access to biological data.

The EnsMart system (www.ensembl.org/EnsMart) provides a generic data warehousing solution for fast and flexible querying of large biological data sets and integration with third-party data and tools. The system consists of a query-optimized database and interactive, user-friendly interfaces. EnsMart has been applied to Ensembl, where it extends its genomic browser capabilities, facilitating rapid retrieval of customized data sets. A wide variety of complex queries, on various types of annotations, for numerous species are supported. These can be applied to many research problems, ranging from SNP selection for candidate gene screening, through cross-species evolutionary comparisons, to microarray annotation. Users can group and refine biological data according to many criteria, including cross-species analyses, disease links, sequence variations, and expression patterns. Both tabulated list data and biological sequence output can be generated dynamically, in HTML, text, Microsoft Excel, and compressed formats. A wide range of sequence types, such as cDNA, peptides, coding regions, UTRs, and exons, with additional upstream and downstream regions, can be retrieved. The EnsMart database can be accessed via a public Web site, or through a Java application suite. Both implementations and the database are freely available for local installation, and can be extended or adapted to 'non-Ensembl' data sets.

Animals↗

PubMed2000

It's time: record linkage--the vision and the reality.

OBJECTIVE: To examine reasons for the minimal use of Australian administrative health data for research and evaluation. METHOD: Legislative, organisational, social and political barriers in Australia are described. RESULTS: System changes are identified that would support the implementation of an evaluation-oriented health data collection system. A Universal Patient Identifier is essential. Leadership and funding at the federal level will be required to ensure the co-ordinated introduction of a rational and integrated health data system in Australia. CONCLUSIONS: Health data in Australia is not currently collected in a manner that allows the assessment of health outcomes. It is time to change the basis of health data collection from accounting to health outcomes evaluation and to reorganise the system to support this. IMPLICATIONS: If appropriate national health data were available, research and evaluation of services could be undertaken and treatment outcomes and adverse events could be monitored. Such information could provide a basis for targeted clinical trials and provide evidence for best clinical practice.

Australia↗

PubMed2005

Application of DNA microarray technology in determining breast cancer prognosis and therapeutic response.

There are > 1.15 million cases of breast cancer diagnosed worldwide annually, and it is the second leading cause of cancer death in the European Union. The optimum management of patients with breast cancer requires accurate prognostic and predictive factors. At present, only a small number of such factors are used clinically. DNA microarrays have the potential to measure the expression of tens of thousands of genes simultaneously. Recent preliminary findings suggest that DNA microarray-based gene expression profiling can provide powerful and independent prognostic information in patients with newly diagnosed breast cancer. As well as providing prognostic information, emerging results suggest that DNA microarrays can also be used for predicting response or resistance to treatment, especially to neoadjuvant chemotherapy. Prior to clinical application, these preliminary findings must be validated using large-scale prospective studies. This article reviews these advances and also examines the role of DNA microarrays in reducing the number of patients who receive inappropriate chemotherapy. The most recent data supporting the integration of various publicly available data sets is also reviewed in detail.

Breast Neoplasms↗

PubMed2006

Validation of commercial DNA tests for quantitative beef quality traits.

Associations between 3 commercially available genetic marker panels (GeneSTAR Quality Grade, GeneSTAR Tenderness, and Igenity Tender-GENE) and quantitative beef traits were validated by the US National Beef Cattle Evaluation Consortium. Validation was interpreted to be the independent confirmation of the associations between genetic tests and phenotypes, as claimed by the commercial genotyping companies. Validation of the quality grade test (GeneSTAR Quality Grade) was carried out on 400 Charolais x Angus crossbred cattle, and validation of the tenderness tests (GeneSTAR Tenderness and Igenity Tender-GENE) was carried out on over 1,000 Bos taurus and Bos indicus cattle. The GeneSTAR Quality Grade marker panel is composed of 2 markers (TG5, a SNP upstream from the start of the first exon of thyroglobulin, and QG2, an anonymous SNP) and is being marketed as a test associated with marbling and quality grade. In this validation study, the genotype results from this test were not associated with marbling score; however, the association of substituting favorable alleles of the marker panel with increased quality grade (percentage of cattle grading Choice or Prime) approached significance (P < or = 0.06), mainly due to the effect of 1 of the 2 markers. The GeneSTAR Tenderness and Igenity TenderGENE marker panels are being marketed as tests associated with meat tenderness, as assessed by Warner-Bratzler shear force. These marker panels share 2 common mu-calpain SNP, but each has a different calpastatin SNP. In both panels, there were highly significant (P < 0.001) associations of the calpastatin marker and the mu-calpain haplotype with tenderness. The genotypic effects of the 2 tenderness panels were similar to each other, with a 1 kg difference in Warner-Bratzler shear force being observed between the most and least tender genotypes. Unbiased and independent validation studies are important to help build confidence in marker technology and also as a potential source of data required to enable the integration of marker data into genetic evaluations. As DNA tests associated with more beef production traits enter the marketplace, it will become increasingly important, and likely more difficult, to find independent populations with suitable phenotypes for validation studies.

Alleles↗

PubMed2006

Cruella: developing a scalable tissue microarray data management system.

CONTEXT: Compared with DNA microarray technology, relatively little information is available concerning the special requirements, design influences, and implementation strategies of data systems for tissue microarray technology. These issues include the requirement to accommodate new and different data elements for each new project as well as the need to interact with pre-existing models for clinical, biological, and specimen-related data. OBJECTIVE: To design and implement a flexible, scalable tissue microarray data storage and management system that could accommodate information regarding different disease types and different clinical investigators, and different clinical investigation questions, all of which could potentially contribute unforeseen data types that require dynamic integration with existing data. DESIGN: The unpredictability of the data elements combined with the novelty of automated analysis algorithms and controlled vocabulary standards in this area require flexible designs and practical decisions. Our design includes a custom Java-based persistence layer to mediate and facilitate interaction with an object-relational database model and a novel database schema. User interaction is provided through a Java Servlet-based Web interface. RESULTS: Cruella has become an indispensable resource and is used by dozens of researchers every day. The system stores millions of experimental values covering more than 300 biological markers and more than 30 disease types. The experimental data are merged with clinical data that has been aggregated from multiple sources and is available to the researchers for management, analysis, and export. CONCLUSION: Cruella addresses many of the special considerations for managing tissue microarray experimental data and the associated clinical information. A metadata-driven approach provides a practical solution to many of the unique issues inherent in tissue microarray research, and allows relatively straightforward interoperability with and accommodation of new data models.

Database Management Systems↗

PubMed1994

Physicians in health care management: 6. Physician bytes computer.

Revolutionary advancements in information technology are improving access to medical information, operational efficiency and clinical effectiveness. Health care facilities and agencies are planning to acquire information systems that will affect clinical and administrative functions. Federal and provincial agencies are beginning to define and collect diverse health care data and integrate them in a national database. As the demand for and access to information grows physicians will be key providers and users. They will have increasing access to critical patient data through clinical information systems; however, their practice patterns, clinical outcomes and resource utilization will also be subject to increasing scrutiny. To ensure appropriate use of technology and information systems, careful planning, selection, implementation and management will be needed. Physicians will require training to use the information and systems effectively. They must also recognize the increasing importance of such systems in delivering and managing health care; they must play a pivotal role in resolving management, information and systems issues and in promoting sound information and management strategies; and they must encourage research and education in medical informatics.

Attitude to Computers↗

PubMed2001

Multimodal cranial neuronavigation: direct integration of functional magnetic resonance imaging and positron emission tomography data: technical note.

OBJECTIVE: This is the first report of the direct integration of functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) data into cranial neuronavigation. METHODS: In a patient with a left precentral oligodendroglioma (World Health Organization Grade III), the Zeiss MKM system (Carl Zeiss Co., Oberkochen, Germany) was used for navigation based on thin-slice, T1-weighted, contrast-enhanced magnetic resonance imaging (MRI) scans. fMRI and methionine PET data were integrated by landmark matching, with reference to skin fiducials. RESULTS: The inaccuracy of the image fusion between fMRI and T1-weighted MRI data was 1.7 mm, that between PET and T1-weighted MRI data was 4.3 mm, and that for the subsequent registration of the navigation was 1.2 mm. The correct fMRI localization of the precentral gyrus was intraoperatively verified by cortical somatosensory evoked potential (phase-reversal) monitoring. Although the tumor was not clearly defined in the MRI scans, [11C]methionine PET demonstrated a clear tumor border, enabling us to achieve gross total tumor removal without postoperative functional deficits. CONCLUSION: Functional neuronavigation permits observation and preservation of relevant brain areas. Other functional areas (such as short-term memory areas) that can be detected only by fMRI might also warrant future monitoring. The simultaneous integration of fMRI and PET data adds a new dimension to cranial neuronavigation, enabling the observation of tumors in relation to functional cortical areas (in our case, the motor strip).

Brain↗

PubMed2003

Characterization of the low-copy HERV-Fc family: evidence for recent integrations in primates of elements with coding envelope genes.

In a previous search based on the envelope gene, we had identified two related proviral elements that could not be included in identified ERV families. An in silico database screening associated with an in vivo polymerase chain reaction search using primers in the reverse transcriptase domain, now allowed identification of a series of related elements, found at a limited number in simians. A phylogenetic analysis led to their inclusion in a new family of endogenous retroviruses with limited expansion, which we named ERV-Fc, and which is part of the enlarged ERV-F/H family. The human genome comprises only six HERV-Fc, among which two possess full-length coding envelope genes. A complete provirus was identified in the baboon, also disclosing a fully open envelope gene. Cloning of the sites orthologous to the envelope-coding human proviruses demonstrated presence of the integrated proviruses in chimpanzee and gorilla, but not in orangutan. For the baboon element, the orthologous locus was found empty even in the phylogenetically most closely related macaque, again suggesting, together with the complete identity of its LTRs, "recent" integration. The data presented are compatible with an evolutionary scheme in which the ERV-Fc proviruses would be the endogenous traces of an active retroviral element, possibly acting as an infectious retrovirus with low endogeneization potency, with evidence for integrations at two distinct periods of primate evolution.

Amino Acid Sequence↗

PubMed2000

Outdoor air concentrations of nitrogen dioxide and sulfur dioxide and prevalence of wheezing in school children.

We report analysis of data on outdoor air pollution and respiratory symptoms in children collected in the Czech part of the international Small Area Variations in Air pollution and Health (SAVIAH) Project, a methodological study designed to test the use of geographical information systems (GIS) in studies of environmental exposures and health at small area level. We collected the following data in two districts of Prague: (1) individual data on 3,680 children (response rate 88%) by questionnaires; (2) census-based socio-demographic data for small geographical units; (3) concentrations of nitrogen dioxide (NO2) and sulfur dioxide (SO2) measured by passive samplers in three 2-week surveys at 80 and 50 locations, respectively. We integrated all data into a geographical information system. Modeling of NO2 and SO2 allowed estimation of exposure to outdoor NO2 and SO2 at school and at home for each child. We examined the associations between air pollution and prevalence of wheezing or whistling in the chest in the last 12 months by logistic regression at individual level, weighted least squares regression at small area (ecological) level and multilevel modeling. The results varied by the level of analysis and method of exposure estimation. In multilevel analyses using individual data, odds ratios per 10 microg/m3 increase in concentrations were 1.16 (95% CI = 0.95-1.42) for NO2, and 1.08 (95% CI = 0.97-1.21) for SO2. While mapping of spatial distribution of NO2 and SO2 in the study area appeared valid, the interpolation from outdoor to personal exposures requires consideration.

Air Pollutants↗

PubMed1976

25. Colorado long-term care statistical reporting system.

The long-term care data system being developed in Colorado is based on a patient-oriented approach. Patient descriptors and corresponding care needs are used to determine optimum care environments, and to construct an integrated patient/facility data base for evaluating patient care. Simultaneously, the Colorado project is developing an automated, interactive data system that will assist the programs for state licensure and federal certification of long-term health facilities and provide data on patients and facilities for the Cooperative Health Statistics System (CHSS) and state and local agencies.

Colorado↗

PubMed2002

Computational function assignment for potential drug targets: from single genes to cellular systems.

Biomedical science is currently undergoing an epoch-marking transition from its classical phase to the post-genome era. The outstanding success of world-wide genome sequencing efforts, evidenced by the recent publication of the draft of the human genome, together with the completion of several genomes of eukaryotic model organisms and the availability of microbial genome sequences, is opening up data sources of unprecedented scale for drug discovery. Furthermore, the elucidation of genome expression states through transcriptomic and proteomic techniques is playing a crucial role in the characterisation of disease at the molecular level. At the same time, our still very limited knowledge of the biological functions of genes and proteins at different levels of cellular organisation is preventing full exploitation of the available data. This review will discuss current computational techniques for function prediction based on the sequence-structure-function paradigm. Newly emerging approaches aimed at gaining an expanded understanding of function through integration of data from various sources and modelling of complex cellular systems will also be highlighted.

Amino Acid Sequence↗

PubMed2006

STRING 7--recent developments in the integration and prediction of protein interactions.

Information on protein-protein interactions is still mostly limited to a small number of model organisms, and originates from a wide variety of experimental and computational techniques. The database and online resource STRING generalizes access to protein interaction data, by integrating known and predicted interactions from a variety of sources. The underlying infrastructure includes a consistent body of completely sequenced genomes and exhaustive orthology classifications, based on which interaction evidence is transferred between organisms. Although primarily developed for protein interaction analysis, the resource has also been successfully applied to comparative genomics, phylogenetics and network studies, which are all facilitated by programmatic access to the database backend and the availability of compact download files. As of release 7, STRING has almost doubled to 373 distinct organisms, and contains more than 1.5 million proteins for which associations have been pre-computed. Novel features include AJAX-based web-navigation, inclusion of additional resources such as BioGRID, and detailed protein domain annotation. STRING is available at http://string.embl.de/

Databases, Protein↗

PubMed2005

The integrated epidemiologic profile: using multiple data sources in developing profiles to inform HIV prevention and care planning.

HIV/AIDS epidemiologic profiles describe the HIV/AIDS epidemic among state and local populations. The Centers for Disease Control and Prevention and the Health Resources Services Administration collaborated to develop one set of guidelines for developing epidemiologic profiles that would serve as the basis for both prevention and care planning. The Integrated Guidelines for Developing Epidemiologic Profiles was published in 2003. Profiles based on these guidelines describe the epidemic in terms of sociodemographic, geographic, behavioral, and clinical characteristics and should include enough data sources (e.g., sexually transmitted disease, tuberculosis, behavioral, and care-related data) to allow users to make informed, evidenced-based decisions. Development and use of these epidemiologic profiles should lead to more effective prevention and care planning and contribute to objective measures of the impact and outcomes of programs, supported by both federal agencies.

Data Collection↗

PubMed1989

The data dictionary--a controlled vocabulary for integrating clinical databases and medical knowledge bases.

The medical information systems of the future will probably include the entire medical record as well as a knowledge base, providing decision support for the physician during patient care. Data dictionaries will play an important role in integrating the medical knowledge bases with the clinical databases. This article presents an infological data model of such an integrated medical information system. Medical events, medical terms, and medical facts are the basic concepts that constitute the model. To allow the transfer of information and knowledge between systems, the data dictionary should be organized with regard to several common classification schemes of medical nomenclature.

Database Management Systems↗

PubMed2001

Interspecies conservation of gene order and intron-exon structure in a genomic locus of high gene density and complexity in Plasmodium.

A 13.6 kb contig of chromosome 5 of Plasmodium berghei, a rodent malaria parasite, has been sequenced and analysed for its coding potential. Assembly and comparison of this genomic locus with the orthologous locus on chromosome 10 of the human malaria Plasmodium falciparum revealed an unexpectedly high level of conservation of the gene organisation and complexity, only partially predicted by current gene-finder algorithms. Adjacent putative genes, transcribed from complementary strands, overlap in their untranslated regions, introns and exons, resulting in a tight clustering of both regulatory and coding sequences, which is unprecedented for genome organisation of PLASMODIUM: In total, six putative genes were identified, three of which are transcribed in gametocytes, the precursor cells of gametes. At least in the case of two multiple exon genes, alternative splicing and alternative transcription initiation sites contribute to a flexible use of the dense information content of this locus. The data of the small sample presented here indicate the value of a comparative approach for Plasmodium to elucidate structure, organisation and gene content of complex genomic loci and emphasise the need to integrate biological data of all Plasmodium species into the P.falciparum genome database and associated projects such as PlasmodB to further improve their annotation.

Alternative Splicing↗

PubMed2005

Molecular alterations in primary prostate cancer after androgen ablation therapy.

PURPOSE: After an initial response to androgen ablation, most prostate tumors recur, ultimately progressing to highly aggressive androgen-independent cancer. The molecular mechanisms underlying progression are not well known in part due to the rarity of androgen-independent samples from primary and metastatic sites. EXPERIMENTAL DESIGN: We compared the gene expression profiles of 10 androgen-independent primary prostate tumor biopsies with 10 primary, untreated androgen-dependent tumors. Samples were laser capture microdissected, the RNA was amplified, and gene expression was assessed using Affymetrix Human Genome U133A GeneChip. Differential expression was examined with principal component analysis, hierarchical clustering, and Student's t testing. Analysis of gene ontology was done with Expression Analysis Systematic Explorer and gene expression data were integrated with genomic alterations with Differential Gene Locus Mapping. RESULTS: Unsupervised principal component analysis showed that the androgen-dependent and androgen-independent tumors segregated from one another. After filtering the data, 239 differentially expressed genes were identified. Two main gene ontologies were found discordant between androgen-independent and androgen-dependent tumors: macromolecule biosynthesis was down-regulated and cell adhesion was up-regulated in androgen-independent tumors. Other differentially expressed genes were related to interleukin-6 signaling as well as angiogenesis, cell adhesion, apoptosis, oxidative stress, and hormone response. The Differential Gene Locus Mapping analysis identified nine regions of potential chromosomal deletion in the androgen-independent tumors, including 1p36, 3p21, 6p21, 8p21, 11p15, 11q12, 12q23, 16q12, and 16q21. CONCLUSIONS: Taken together, these data identify several unique characteristics of androgen-independent prostate cancer that may hold potential for the development of targeted therapeutic intervention.

Aged↗