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PubMed1997

A network of web multimedia medical information servers for a medical school and university hospital.

Modern medicine requires a rapid access to information including clinical data from medical records, bibliographic databases, knowledge bases and nomenclature databases. This is especially true for University Hospitals and Medical Schools for training as well as for fundamental and clinical research for diagnosis and therapeutic purposes. This implies the development of local, national and international cooperation which can be enhanced via the use and access to computer networks such as Internet. The development of professional cooperative networks goes with the development of the telecommunication and computer networks and our project is to make these new tools and technologies accessible to the medical students both during the teaching time in Medical School and during the training periods at the University Hospital. We have developed a local area network which communicates between the School of Medicine and the Hospital which takes advantage of the new Web client-server technology both internally (Intranet) and externally by access to the National Research Network (RENATER in France) connected to the Internet network. The address of our public web server is http:(/)/www.med.univ-rennesl.fr.

Artificial Intelligence↗
PubMed2005

Assigning new GO annotations to protein data bank sequences by combining structure and sequence homology.

Accompanying the discovery of an increasing number of proteins, there is the need to provide functional annotation that is both highly accurate and consistent. The Gene Ontology (GO) provides consistent annotation in a computer readable and usable form; hence, GO annotation (GOA) has been assigned to a large number of protein sequences based on direct experimental evidence and through inference determined by sequence homology. Here we show that this annotation can be extended and corrected for cases where protein structures are available. Specifically, using the Combinatorial Extension (CE) algorithm for structure comparison, we extend the protein annotation currently provided by GOA at the European Bioinformatics Institute (EBI) to further describe the contents of the Protein Data Bank (PDB). Specific cases of biologically interesting annotations derived by this method are given. Given that the relationship between sequence, structure, and function is complicated, we explore the impact of this relationship on assigning GOA. The effect of superfolds (folds with many functions) is considered and, by comparison to the Structural Classification of Proteins (SCOP), the individual effects of family, superfamily, and fold.

Algorithms↗
PubMed2007

Italian Rett database and biobank.

Rett syndrome is the second most common cause of severe mental retardation in females, with an incidence of approximately 1 out of 10,000 live female births. In addition to the classic form, a number of Rett variants have been described. MECP2 gene mutations are responsible for about 90% of classic cases and for a lower percentage of variant cases. Recently, CDKL5 mutations have been identified in the early onset seizures variant and other atypical Rett patients. While the high percentage of MECP2 mutations in classic patients supports the hypothesis of a single disease gene, the low frequency of mutated variant cases suggests genetic heterogeneity. Since 1998, we have performed clinical evaluation and molecular analysis of a large number of Italian Rett patients. The Italian Rett Syndrome (RTT) database has been developed to share data and samples of our RTT collection with the scientific community (http://www.biobank.unisi.it). This is the first RTT database that has been connected with a biobank. It allows the user to immediately visualize the list of available RTT samples and, using the "Search by" tool, to rapidly select those with specific clinical and molecular features. By contacting bank curators, users can request the samples of interest for their studies. This database encourages collaboration projects with clinicians and researchers from around the world and provides important resources that will help to better define the pathogenic mechanisms underlying Rett syndrome.

Databases as Topic↗
PubMedDate not supplied

Pharmacogenetics and pharmacoepidemiology.

This paper seeks to stimulate consideration of the short- and long-term possibilities raised by research into pharmacogenetics and pharmacoepidemiology, to identify potential tissue databanks linked to population data, and to summarize our ethical responsibilities. Short term, we might identify selected disorders or risk factors, such as for drug-associated serious events, and might find selected target populations. Long term, we might incorporate genomics techniques into population data and map genetic risk factors for diseases and drug responses. Tissue specimens that might be linked to clinical data lie in certain data resources: clinical trials, ad hoc cohorts, case registries, and cross-sectional and longitudinal population samples. Specific areas must be addressed in research using human tissue and genetic material, including the ethical threat to privacy. We must avoid misuse of genetic information by breaching confidentiality and putting at risk specific genetically identifiable groups. The National Bioethics Advisory Commission recently addressed the issue of serum and tissue data banks in a published report summarized in this paper. Social, methodologic, and ethical issues relate to any protocol using serum and tissue, and indicate a need for broad educational efforts. We must set guidelines as pharmacogenetics research becomes a dimension of pharmacoepidemiology.

Cohort Studies↗
PubMed2004

Presentation of differentially regulated proteins within a web-accessible proteome database system of microorganisms.

Web-accessible proteome databases represent indispensable tools for quantitative and comparative proteomics research. The majority of two-dimensional gel electrophoresis (2-DE) databases contains clickable 2-DE gel images and descriptive textual information such as protein name, Mr/pI values, methods of identification, cellular localization and other information on proteins. Although a great part of the work in comparative proteomics consists of the analysis of 2-DE gels using image analysis approaches, most proteome databases lack the ability to present protein abundance data and their alterations within experiments via the web. Now, differentially regulated proteins detected in microbial experiments by quantitative gel image analysis are presented in a web-accessible relational database DIFF (Differentially Regulated Proteins). The DIFF database is a part of the proteome database system for microbial research available at http://www.mpiib-berlin.mpg.de/2D-PAGE.

Bacterial Proteins↗
PubMed2005

PhosphaBase: an ontology-driven database resource for protein phosphatases.

PhosphaBase is an ontology-driven database resource containing information on the protein phosphatase family. It is the first public resource dedicated to protein phosphatases, which are enzymes that perform dephosphorylation reactions. In conjunction with the phosphorylation action of protein kinases, phosphatases are involved in important control and communication mechanisms in the cell. They have also been implicated in many human diseases, including diabetes and obesity, cancers, and neurodegenerative conditions. PhosphaBase aims to centralize the growing base of knowledge in the phosphatase research domain. The resource is built around a formal, domain-specific DAML+OIL ontology, and the data are collected from heterogeneous biological sources using Gene Ontology terms as a means of data extraction. The overall ontology-driven architecture provides a robust structure with distinct advantages for sustainability and provides the potential for the development of diagnostic tools, as well as a data repository.

Animals↗
PubMed2002

A new approach to training back-propagation artificial neural networks: empirical evaluation on ten data sets from clinical studies.

We present a new approach to training back-propagation artificial neural nets (BP-ANN) based on regularization and cross-validation and on initialization by a logistic regression (LR) model. The new approach is expected to produce a BP-ANN predictor at least as good as the LR-based one. We have applied the approach to ten data sets of biomedical interest and systematically compared BP-ANN and LR. In all data sets, taking deviance as criterion, the BP-ANN predictor outperforms the LR predictor used in the initialization, and in six cases the improvement is statistically significant. The other evaluation criteria used (C-index, MSE and error rate) yield variable results, but, on the whole, confirm that, in practical situations of clinical interest, proper training may significantly improve the predictive performance of a BP-ANN.

Biometry↗
PubMed2002

TAIR: a resource for integrated Arabidopsis data.

The Arabidopsis Information Resource (TAIR; http://arabidopsis.org) provides an integrated view of genomic data for Arabidopsis thaliana. The information is obtained from a battery of sources, including the Arabidopsis user community, the literature, and the major genome centers. Currently TAIR provides information about genes, markers, polymorphisms, maps, sequences, clones, DNA and seed stocks, gene families and proteins. In addition, users can find Arabidopsis publications and information about Arabidopsis researchers. Our emphasis is now on incorporating functional annotations of genes and gene products, genome-wide expression, and biochemical pathway data. Among the tools developed at TAIR, the most notable is the Sequence Viewer, which displays gene annotation, clones, transcripts, markers and polymorphisms on the Arabidopsis genome, and allows zooming in to the nucleotide level. A tool recently released is AraCyc, which is designed for visualization of biochemical pathways. We are also developing tools to extract information from the literature in a systematic way, and building controlled vocabularies to describe biological concepts in collaboration with other database groups. A significant new feature is the integration of the ABRC database functions and stock ordering system, which allows users to place orders for seed and DNA stocks directly from the TAIR site.

Arabidopsis↗
PubMed2005

The Cochrane Skin Group: promoting the best evidence.

BACKGROUND: The international Cochrane Skin group, established in 1997, organizes, writes and disseminates systematic reviews of therapeutic interventions in dermatology. OBJECTIVE: To introduce the Cochrane Skin Group and what it offers to cutaneous medicine and surgery providers. METHODS: Descriptive review of the structure and output of the Cochrane Collaboration Library and the Cochrane Skin Group. RESULTS: Systematic reviews of randomized controlled trials produced through the Cochrane Skin Group provide a benchmark for evidence summaries for informing clinical decisions in dermatology. CONCLUSION: The work performed by the Cochrane Skin Group is an important component for informing the evidence base for the clinical practice of cutaneous and surgical dermatology.

Benchmarking↗
PubMed2005

Proteomic analysis of Bacillus anthracis Sterne vegetative cells.

Mass spectrometry and proteomics have found increasing use as tools for the rapid detection of pathogenic bacteria, even when they are in a mixture of non-pathogenic relatives. The success of this technique is greatly augmented by the availability of publicly accessible proteomic databases for specific pathogenic bacteria. To aid proteomic detection analyses for the causative agent of anthrax, we have constructed a comprehensive proteomic catalogue of vegetative Bacillus anthracis Sterne cells using liquid chromatography tandem-mass spectrometry. Proteins were separated by molecular weight or isoelectric point prior to tryptic digestion. Alternatively, the whole protein extract was digested and tryptic peptides were separated by cation exchange chromatography prior to Reverse Phase-LC-MS/MS. The use of three complementary, pre-analytical separation techniques resulted in the identification of 1048 unique proteins, including 694 cytosolic, 153 membrane (including 27 cell wall), and 30 secreted proteins, accounting for 19% of the total predicted proteome. Each identified protein was functionally categorized using the gene attribute database from TIGR CMR. These results provide a large proteomic catalogue of vegetative B. anthracis cells and, coupled with the recent proteomic catalogue of B. anthracis spore proteins, form a thorough summary of proteins expressed in the active and dormant stages of this organism.

Bacillus anthracis↗
PubMed2005

Patient-recognition data-mining model for BCG-plus interferon immunotherapy bladder cancer treatment.

Bladder cancer is the fifth most common malignant disease in the United States with an annual incidence of around 63,210 new cases and 13,180 deaths. The cost for providing care for patients with bladder cancer disease is high. Bladder cancer treatment options such as immunotherapy, chemotherapy, radiation therapy, transurethral resection, and cystectomy, are used with varying success rates. In this research, data from a nationwide bacillus Calmette-Gue rin (BCG) plus interferon-alpha (IFN-alpha) immunotherapy clinical trial was considered. Data mining algorithms were used to analyze the effectiveness of immunotherapy treatment and to understand the prominent parameters and their interactions. The extracted knowledge was used to build a patient recognition model for prediction of treatment outcomes. The data was analyzed to understand the impact of various parameters on the treatment outcome. A list of significant parameters such as cumulative tumor size, presence of residual disease, stages of prior bladder cancer, current state of bladder cancer, and the presence of current bladder cancer (T1) is provided. The decision-making approach outlined in the paper supplemented with additional knowledge bases will lead to a comprehensive analytical road map of the BCG/IFN-alpha immunotherapy treatment. It will provide individualized guidelines for each stage of the treatment as well as measure the success of the treatment.

Adjuvants, Immunologic↗
PubMed2006

Trends in survival after childhood cancer in Europe, 1978-1997: report from the Automated Childhood Cancer Information System project (ACCIS).

This study, originating in the Automated Childhood Cancer Information System (ACCIS), evaluated the time trend in survival after childhood cancer in Europe. The study included more than 72,000 childhood cancer cases aged 0-14 years diagnosed in 1978-1997 and followed-up in 30 population-based cancer registries with a long history of registration and follow-up, in 15 European countries. Survival was analysed using an actuarial life-table method. Five-year cumulative survival probability increased significantly over the study period for all tumour types combined, from 54% for cases diagnosed in the period 1978-1982 to 75% in 1993-1997. Significant improvement was also observed in 10-year survival. Comparing the results for the period 1993-1997 with those for 1978-1982, the largest relative increase in survival was seen for hepatic tumours (32%) and the largest reduction in mortality for non-Hodgkin's lymphomas (60%). Least progress was seen for central nervous system (CNS) tumours. The improvement was statistically significant in all European regions and was most rapid in the East. The ranking among the European regions did not change over the study period, with highest survival in the North and the West and lowest in the East. Extended data collection is necessary to evaluate future time trends and changes in differences between European regions.

Adolescent↗
PubMed2003

PhysioNet: an NIH research resource for complex signals.

The Research Resource for Complex Physiologic Signals, supported by the National Institutes of Health (NIH), is intended to promote and facilitate investigations in the study of cardiovascular and other complex biomedical signals. The resource website (www.physionet.org) has 3 interdependent components: 1) PhysioBank is an archive of well-characterized digital recordings of physiologic signals and related data, including databases of electrocardiogram and heart rate time series from patients with heart failure, coronary disease, sleep apnea syndromes, and cardiac arrhythmias; 2) PhysioToolkit is a library of open-source software for physiologic signal processing and analysis; and 3) PhysioNet, for which the resource is named, is an on-line forum for dissemination and exchange of recorded biomedical signals and open-source software for analyzing them. PhysioNet, in cooperation with the annual Computers in Cardiology conference, hosts a series of challenges inviting participants to tackle clinically interesting problems that are either unsolved or not well solved. PhysioNet invites contributions of databases and software from the biomedical community.

Atrial Fibrillation↗
PubMed2005

Looking at enzymes from the inside out: the proximity of catalytic residues to the molecular centroid can be used for detection of active sites and enzyme-ligand interfaces.

Analysis of the distances of the exposed residues in 175 enzymes from the centroids of the molecules indicates that catalytic residues are very often found among the 5% of residues closest to the enzyme centroid. This property of catalytic residues is implemented in a new prediction algorithm (named EnSite) for locating the active sites of enzymes and in a new scheme for re-ranking enzyme-ligand docking solutions. EnSite examines only 5% of the molecular surface (represented by surface dots) that is closest to the centroid, identifying continuous surface segments and ranking them by their area size. EnSite ranks the correct prediction 1-4 in 97% of the cases in a dataset of 65 monomeric enzymes (rank 1 for 89% of the cases) and in 86% of the cases in a dataset of 176 monomeric and multimeric enzymes from all six top-level enzyme classifications (rank 1 in 74% of the cases). Importantly, identification of buried or flat active sites is straightforward because EnSite "looks" at the molecular surface from the inside out. Detailed examination of the results indicates that the proximity of the catalytic residues to the centroid is a property of the functional unit, defined as the assembly of domains or chains that form the active site (in most cases the functional unit corresponds to a single whole polypeptide chain). Using the functional unit in the prediction further improves the results. The new property of active sites is also used for re-evaluating enzyme-inhibitor unbound docking results. Sorting the docking solutions by the distance of the interface to the centroid of the enzyme improves remarkably the ranks of nearly correct solutions compared to ranks based on geometric-electrostatic-hydrophobic complementarity scores.

Algorithms↗
PubMed2006

Long-term atomoxetine treatment in adolescents with attention-deficit/hyperactivity disorder.

OBJECTIVE: To determine the efficacy and safety of atomoxetine in adolescent subjects treated for attention-deficit/hyperactivity disorder (ADHD) for up to 2 years. STUDY DESIGN: Data from 13 atomoxetine studies (6 double-blind, 7 open-label) were pooled for subjects age 12 to 18 with ADHD as defined by the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders IV. RESULTS: Of the 601 atomoxetine-treated subjects in this meta-analysis, 537 (89.4%) completed 3 months of acute treatment. A total of 259 subjects (48.4%) are continuing atomoxetine treatment; 219 of these subjects have completed at least 2 years of treatment. The mean dose of atomoxetine at endpoint was 1.41 mg/kg/day. Mean ADHD Rating Scale IV, parent version, investigator-administered and -scored total scores showed significant improvement (P < .001) over the first 3 months. Symptoms remained improved up to 24 months without dosage escalation. During the 2-year treatment period, 99 (16.5%) subjects discontinued treatment due to lack of effectiveness, and 31 (5.2%) subjects discontinued treatment due to adverse events. No clinically significant abnormalities in height, weight, blood pressure, pulse, mean laboratory values, or electrocardiography parameters were found. CONCLUSIONS: Two-year data from this ongoing study indicate that atomoxetine maintains efficacy among adolescents with ADHD, with no evidence of drug tolerance and no new or unexpected safety concerns.

Adolescent↗