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At least 1,423 records · Page 79Linked to original sources

DHLAS: A web-based information system for statistical genetic analysis of HLA population data.

DHLAS (database HLA system) is a user-friendly, web-based information system for the analysis of human leukocyte antigens (HLA) data from population studies. DHLAS has been developed using JAVA and the R system, it runs on a Java Virtual Machine and its user-interface is web-based powered by the servlet engine TOMCAT. It utilizes STRUTS, a Model-View-Controller framework and uses several GNU packages to perform several of its tasks. The database engine it relies upon for fast access is MySQL, but others can be used a well. The system estimates metrics, performs statistical testing and produces graphs required for HLA population studies: (i) Hardy-Weinberg equilibrium (calculated using both asymptotic and exact tests), (ii) genetics distances (Euclidian or Nei), (iii) phylogenetic trees using the unweighted pair group method with averages and neigbor-joining method, (iv) linkage disequilibrium (pairwise and overall, including variance estimations), (v) haplotype frequencies (estimate using the expectation-maximization algorithm) and (vi) discriminant analysis. The main merit of DHLAS is the incorporation of a database, thus, the data can be stored and manipulated along with integrated genetic data analysis procedures. In addition, it has an open architecture allowing the inclusion of other functions and procedures.

Databases, Genetic↗

Myocardial viability in patients with ischemic cardiomyopathy-evaluation by 3-D integration of myocardial scintigraphic data--and coronary angiographic data.

PURPOSE: To determine the prevalence of viable myocardium in patients with ischemic cardiomyopathy and, to evaluate the value of three-dimensional (3-D) fusion imaging of myocardial scintigraphic and angiographic data to assign coronary artery lesions to the corresponding viable and nonviable myocardial territory. PROCEDURES: In 105 patients, the combination of perfusion and metabolic imaging with (201)thallium ((201)TI) single-photon emission computed tomography (SPECT) and 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) positron emission tomography (PET) determined viability in dysfunctional myocardium. In addition, the value of 3-D scintigraphic fusion imaging was assessed in these patients. RESULTS: Based on the presence of viable dysfunctional myocardium, 54% of patients with ischemic cardiomyopathy may be considered for coronary revascularization. In 31 of 105 patients, the 3-D fusion imaging was estimated to be helpful in the diagnostic and interpretative process. CONCLUSION: In patients with end-stage coronary artery disease scintigraphic imaging is most important in the decision-making process. Three-dimensional fusion imaging may add important information in approximately 30% of these patients.

Aged↗

Parametric design and correlational analyses help integrating fMRI and electrophysiological data during face processing.

Face perception is typically associated with activation in the inferior occipital, superior temporal (STG), and fusiform gyri (FG) and with an occipitotemporal electrophysiological component peaking around 170 ms on the scalp, the N170. However, the relationship between the N170 and the multiple face-sensitive activations observed in neuroimaging is unclear. It has been recently shown that the amplitude of the N170 component monotonically decreases as gaussian noise is added to a picture of a face [Jemel et al., 2003]. To help clarify the sources of the N170 without a priori assumptions regarding their number and locations, ERPs and fMRI were recorded in five subjects in the same experiment, in separate sessions. We used a parametric paradigm in which the amplitude of the N170 was modulated by varying the level of noise in a picture, and identified regions where the percent signal change in fMRI correlated with the ERP data. N170 signals were observed for pictures of both cars and faces but were stronger for faces. A monotonic decrease with added noise was observed for the N170 at right hemisphere sites but was less clear on the left and occipital central sites. Correlations between fMRI signal and N170 amplitudes for faces were highly significant (P < 0.001) in bilateral fusiform gyrus and superior temporal gyrus. For cars, the strongest correlations were observed in the parahippocampal region and in the STG (P < 0.005). Besides contributing to clarify the spatiotemporal course of face processing, this study illustrates how ERP information may be used synergistically in fMRI analyses. Parametric designs may be developed further to provide some timing information on fMRI activity and help identify the generators of ERP signals.

Adult↗

[Neurophysiological data on transmission and integration of nociceptive messages (author's transl)].

In this study cutaneous nociceptive messages are followed at different levels of the CNS, from the periphery to the cortex. A brief summary is given concerning the role of the fine myelinated and unmyelinated fibres which are specifically activated by noxious stimuli. A more extensive review considers the spinal mechanisms which sustain the transmission of nociceptive messages; the electrophysiological properties of interneurones located in laminae VIII, V, and I of the dorsal horn are described in detail. At the same time, the problem of the ascending projections of those cells activated by nociceptive stimuli is discussed. Particular attention is paid to the controls acting at the spinal level: segmental controls are described first and lead to discussion of the "gate control theory"; descending inhibitory controls are then discussed and their importance emphasized. The complexity of pain mechanisms at the supra-spinal level is underlined and a brief review considers the role of various bulbar, mesencephalic and thalamic structures involved in transmission of noxious messages. Among these structures, the PO group of nuclei seem to have a particular role in pain processes. Although the importance of the cortex for final integration of nociceptive messages is discussed, a brief summary is also given of investigations into the role of somatic area SII.

Afferent Pathways↗

Evaluation of the role of intestinal and liver metabolism in the conversion of two different ester prodrugs of sanfetrinem to the parent drug in vitro and in vivo using different rat tissues and a surgically prepared rat model.

To improve oral absorption of sanfetrinem, a broad-spectrum, beta-lactamase-stable antibiotic, two different ester prodrugs have been selected. Both prodrugs proved to be readily hydrolyzed after absorption before reaching the systemic circulation. The objective of this study was to evaluate the role of intestinal and liver metabolism in the conversion of the two prodrugs into the active compound. In vitro experiments were performed in different rat tissues involved in the absorption process. Moreover data obtained with in vitro experiments have been integrated with data obtained in vivo using a surgically prepared rat model which allows for the measurement of the amount of intact prodrug that overcomes the intestinal mucosa and its presence in the portal vein. Both prodrugs proved to be readily cleaved by jejunum and liver microsomes. The rates of ester hydrolysis with these two tissues were 10- to 30-fold higher than those calculated in intestinal juice at pH 7.4 and about 100-fold higher than in buffer at pH 5.5. These data suggest that both the intestinal wall and liver could play an important role in the conversion of the two prodrugs in active parent compound. In the in vivo experiment, relative to sanfetrinem levels, very low concentrations of intact esters were measured in the portal vein blood, indicating that the two prodrugs are nearly completely hydrolyzed to the active drug by the intestinal wall. In conclusion this study demonstrated that the intestinal epithelium plays a major role in the conversion of the two prodrugs into sanfetrinem. The liver, despite its high esterase activity seems to be only marginally involved.

Administration, Oral↗

Interspecies scaling of bosentan, a new endothelin receptor antagonist and integration of in vitro data into allometric scaling.

PURPOSE: The goal of this study was to find a rational and reliable method of using animal data to predict the clearance of metabolised drugs in humans. METHODS: One such approach is to use in vitro liver models (e.g. hepatocytes and microsomes) to determine the relative capacities of the various animal species and humans to metabolise the test compound. These data can then be combined with the in vivo clearances in animals, to calculate the in vivo clearance in humans using allometric scaling techniques. In this study, this approach was evaluated with a new endothelin receptor antagonist, bosentan, which is eliminated mainly through metabolism and is characterized by very large interspecies differences in clearance. Therefore, this compound provided a stringent test of our new extrapolation method for allometric scaling. RESULTS: The results obtained with bosentan showed that adjusting the in vivo clearance in the different animal species for the relative rates of metabolism in vitro gave a far better prediction of human clearance than an empirical correcting factor (brain weight). CONCLUSIONS: This approach provided a more rational basis for predicting the clearance of metabolised compounds in humans.

Animals↗

3-d source localization of epileptic foci integrating EEG and MRI data.

This study evaluates the utility of 3-D localization of interictal spike activity on the electroencephalographs (EEG) superimposed on magnetic resonance imagery (MRI) in a pediatric population with extra-temporal lesional epileptic foci. 3-D software programming based on the CURRY platform (a multimodal neuro-imaging software) was adapted for analyzing scalp EEG data and reconstructing superimposed images in 10 children who underwent extensive pre-surgical evaluation for intractable partial seizures. The results of 3-D spike source localization were assessed in relationship to focal lesions evident on the patient's MRI scans. Calculated spike sources were closest to the lesions during intervals corresponding to the spike peaks. The information was useful in surgical planning in six children that underwent successful resections.

Action Potentials↗

Intensity dependence of perceived duration: data, theories, and neural integration.

Evaluates 2 theoretical models suggested to explain studies of the effect of stimulus intensity on the perceived duration of brief light flashes. Some studies found a direct relationship between the 2 variables; others found an indirect relationship. Each model suggests that an additional variable interacts with stimulus intensity. Proposed variables have included the nature of the judgment and the absolute intensity. The present evaluation indicates that both of the proposed variables play a role and that a melding of the models could best account for this phenomenon. The melding incorporates known time- and intensity-dependent characteristics of neural integration into the behavioral performance. The evaluation also indicates that future experiments on this problem will be most informative if they (a) give particular attention to the role of instructions, (b) explore an adequate range of intensities, and (c) strictly control adaptive state.

Arousal↗

A multifunction network of computers in a large pathology department. Integration of word processing, data base management, and general purpose computing using network principles.

We report the strategies for design and implementation of a system of compatible mini- and microcomputers intended to improve efficiency of data handling and research in several clinical and academic divisions of a large university hospital department of Pathology. A dedicated, preprogrammed, multiuser, word processing computer and small standalone word processing stations connected to a general purpose minicomputer, using standard network protocols for communication, permit virtually error-free movement of data between computers doing functionally distinct tasks of word processing, data base management, and general scientific computing. User programming is minimized and is done in a simple, well-known, high-level language. We show that cost, thruput, speed, document volume, document size, revision cycle frequency, data base size, and frequency of use are important design criteria and that existing staff can be trained easily to operate the systems.

Computers↗

DeeDeeExperiment: building an infrastructure for integrating and managing omics data analysis results in R/Bioconductor.

SUMMARY: Modern omics experiments now involve multiple conditions and complex designs, producing an increasingly large set of differential expression and functional enrichment analysis results. However, no standardized data structure exists to store and contextualize these results together with their metadata, leaving researchers with an unmanageable and potentially non-reproducible collection of results that are difficult to navigate and/or share. Here we introduce DeeDeeExperiment, a new S4 class for managing and storing omics data analysis results, implemented within the Bioconductor ecosystem, which promotes interoperability, reproducibility and good documentation. This class extends the widely used SingleCellExperiment object by introducing dedicated slots for Differential Expression (DEA) and Functional Enrichment Analysis (FEA) results, allowing users to organize, store, and retrieve information on multiple contrasts and associated metadata within a single data object, ultimately streamlining the management and interpretation of many omics datasets. AVAILABILITY AND IMPLEMENTATION: DeeDeeExperiment is available on Bioconductor under the MIT license (https://bioconductor.org/packages/DeeDeeExperiment), with its development version also available on Github (https://github.com/imbeimainz/DeeDeeExperiment).

Software↗

BRIDGE: an interactive application for multi-omics data analysis, visualization and integration.

SUMMARY: BRIDGE is a Shiny-based application that provides an accessible, modular platform for individual and integrative multi-omics analysis. Using an independent SQLite database backend, it offers a local, private, and user-friendly environment that requires no prior computational expertise. The application supports proteomics, phospho-proteomics, and RNA-seq analyses through a comprehensive suite of visualization and analytical modules, together with an integrated multi-omics analysis pipeline. Built-in caching and asynchronous processing improve responsiveness, enabling efficient exploration, analysis, and visualization of multi-omics datasets on moderate hardware. AVAILABILITY AND IMPLEMENTATION: BRIDGE is implemented in R using Shiny and is freely available as a Docker container at https://ghcr.io/paulilab/bridge. A public demonstration server with example datasets is available at https://bridge.imp.ac.at. Code and datasets are also available at https://github.com/paulilab/BRIDGE and under DOI: https://doi.org/10.5281/zenodo.20215824.

Multiomics↗

SPINE: an integrated tracking database and data mining approach for identifying feasible targets in high-throughput structural proteomics.

High-throughput structural proteomics is expected to generate considerable amounts of data on the progress of structure determination for many proteins. For each protein this includes information about cloning, expression, purification, biophysical characterization and structure determination via NMR spectroscopy or X-ray crystallography. It will be essential to develop specifications and ontologies for standardizing this information to make it amenable to retrospective analysis. To this end we created the SPINE database and analysis system for the Northeast Structural Genomics Consortium. SPINE, which is available at bioinfo.mbb.yale.edu/nesg or nesg.org, is specifically designed to enable distributed scientific collaboration via the Internet. It was designed not just as an information repository but as an active vehicle to standardize proteomics data in a form that would enable systematic data mining. The system features an intuitive user interface for interactive retrieval and modification of expression construct data, query forms designed to track global project progress and external links to many other resources. Currently the database contains experimental data on 985 constructs, of which 740 are drawn from Methanobacterium thermoautotrophicum, 123 from Saccharomyces cerevisiae, 93 from Caenorhabditis elegans and the remainder from other organisms. We developed a comprehensive set of data mining features for each protein, including several related to experimental progress (e.g. expression level, solubility and crystallization) and 42 based on the underlying protein sequence (e.g. amino acid composition, secondary structure and occurrence of low complexity regions). We demonstrate in detail the application of a particular machine learning approach, decision trees, to the tasks of predicting a protein's solubility and propensity to crystallize based on sequence features. We are able to extract a number of key rules from our trees, in particular that soluble proteins tend to have significantly more acidic residues and fewer hydrophobic stretches than insoluble ones. One of the characteristics of proteomics data sets, currently and in the foreseeable future, is their intermediate size ( approximately 500-5000 data points). This creates a number of issues in relation to error estimation. Initially we estimate the overall error in our trees based on standard cross-validation. However, this leaves out a significant fraction of the data in model construction and does not give error estimates on individual rules. Therefore, we present alternative methods to estimate the error in particular rules.

Animals↗

Diversification of Neoaves: integration of molecular sequence data and fossils.

Patterns of diversification and timing of evolution within Neoaves, which includes almost 95% of all bird species, are virtually unknown. On the other hand, molecular data consistently indicate a Cretaceous origin of many neoavian lineages and the fossil record seems to support an Early Tertiary diversification. Here, we present the first well-resolved molecular phylogeny for Neoaves, together with divergence time estimates calibrated with a large number of stratigraphically and phylogenetically well-documented fossils. Our study defines several well-supported clades within Neoaves. The calibration results suggest that Neoaves, after an initial split from Galloanseres in Mid-Cretaceous, diversified around or soon after the K/T boundary. Our results thus do not contradict palaeontological data and show that there is no solid molecular evidence for an extensive pre-Tertiary radiation of Neoaves.

Animals↗