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At least 1,117 records · Page 62Linked to original sources

An alternative approach to deal with geometric uncertainties in computer analysis of two-dimensional electrophoresis gels.

With the growing importance of proteomics in biomedical and pharmaceutical sciences a need has emerged for computing tools that are capable of digitally visualizing and analyzing protein spot patterns within two-dimensional electrophoresis (2-DE) gel. Matching programs need to meet requirements such as interlaboratory comparison and the comparison of samples from different origins. For such research purposes, we have developed the CAROL system that implements new algorithms for spot detection and matching, which enable researchers to take a different approach to protein spot identification and comparison. The present short communication discusses how the system deals with uncertain geometric spot information that arises from streaks and complex spot regions and how this can be amplified for the matching procedure.

Algorithms↗

Program in BASIC for Ferguson plot analysis, using a personal computer: application to gel electrophoresis in a continuous buffer.

A program in BASIC suitable for personal computers is described which is applicable to gel electrophoresis conducted in a single (continuous) buffer. The curve fitting is to a polynomial function, allowing for an objective selection of the most appropriate curve type and order--linear, convex or concave--in the particular application. Results do not differ significantly from previous programs for evaluation of linear Ferguson plots or of curve fitting to an exponential function for evaluating convex plots, executed on mainframe computers such as the DEC-10 (Digital) and IBM 370 computers. Thus, the program combines original versatility with, for the first time, the possibility for widespread application of Ferguson plot analysis on personal computers.

Blood Protein Electrophoresis↗

LOVD: easy creation of a locus-specific sequence variation database using an "LSDB-in-a-box" approach.

The completion of the human genome project has initiated, as well as provided the basis for, the collection and study of all sequence variation between individuals. Direct access to up-to-date information on sequence variation is currently provided most efficiently through web-based, gene-centered, locus-specific databases (LSDBs). We have developed the Leiden Open (source) Variation Database (LOVD) software approaching the "LSDB-in-a-Box" idea for the easy creation and maintenance of a fully web-based gene sequence variation database. LOVD is platform-independent and uses PHP and MySQL open source software only. The basic gene-centered and modular design of the database follows the recommendations of the Human Genome Variation Society (HGVS) and focuses on the collection and display of DNA sequence variations. With minimal effort, the LOVD platform is extendable with clinical data. The open set-up should both facilitate and promote functional extension with scripts written by the community. The LOVD software is freely available from the Leiden Muscular Dystrophy pages (www.DMD.nl/LOVD/). To promote the use of LOVD, we currently offer curators the possibility to set up an LSDB on our Leiden server.

Computational Biology↗

EPI image reconstruction with correction of distortion and signal losses.

PURPOSE: To derive and implement a method for correcting geometric distortions and recovering magnetic resonance imaging (MRI) signal losses caused by susceptibility-induced magnetic field gradients (SFGs) in regions with large static field inhomogeneities in echo-planar imaging (EPI). MATERIALS AND METHODS: Factors to account for field inhomogeneities and SFGs were added in a traditional EPI equation that was a simple Fourier transform (FT) for expressing the actual k-space data of an EPI scan. The inverse calculation of this "distorted EPI" equation was used as a kernel to correct geometric distortions and reductions in intensity during reconstruction. A step-by-step EPI reconstruction method was developed to prevent complicated phase unwrapping problems. Some EPI images of phantom and human brains were reconstructed from standard EPI k-spaces. RESULTS: All images were reconstructed using the proposed multistep method. Geometric distortions were corrected and SFG-induced MRI signal losses were recovered. CONCLUSION: Results suggest that applying our method for reconstructing EPI images to reduce distortions and MRI signal losses is feasible.

Algorithms↗

PRIDE: the proteomics identifications database.

The advent of high-throughput proteomics has enabled the identification of ever increasing numbers of proteins. Correspondingly, the number of publications centered on these protein identifications has increased dramatically. With the first results of the HUPO Plasma Proteome Project being analyzed and many other large-scale proteomics projects about to disseminate their data, this trend is not likely to flatten out any time soon. However, the publication mechanism of these identified proteins has lagged behind in technical terms. Often very long lists of identifications are either published directly with the article, resulting in both a voluminous and rather tedious read, or are included on the publisher's website as supplementary information. In either case, these lists are typically only provided as portable document format documents with a custom-made layout, making it practically impossible for computer programs to interpret them, let alone efficiently query them. Here we propose the proteomics identifications (PRIDE) database (http://www.ebi.ac.uk/pride) as a means to finally turn publicly available data into publicly accessible data. PRIDE offers a web-based query interface, a user-friendly data upload facility, and a documented application programming interface for direct computational access. The complete PRIDE database, source code, data, and support tools are freely available for web access or download and local installation.

Computational Biology↗

Further steps in standardisation. Report of the second annual Proteomics Standards Initiative Spring Workshop (Siena, Italy 17-20th April 2005).

The spring workshop of the HUPO-PSI convened in Siena to further progress the data standards which are already making an impact on data exchange and deposition in the field of proteomics. Separate work groups pushed forward existing XML standards for the exchange of Molecular Interaction data (PSI-MI, MIF) and Mass Spectrometry data (PSI-MS, mzData) whilst significant progress was made on PSI-MS' mzIdent, which will allow the capture of data from analytical tools such as peak list search engines. A new focus for PSI (GPS, gel electrophoresis) was explored; as was the need for a common representation of protein modifications by all workers in the field of proteomics and beyond. All these efforts are contextualised by the work of the General Proteomics Standards workgroup; which in addition to the MIAPE reporting guidelines, is continually evolving an object model (PSI-OM) from which will be derived the general standard XML format for exchanging data between researchers, and for submission to repositories or journals.

Mass Spectrometry↗

MASCOT HTML and XML parser: an implementation of a novel object model for protein identification data.

Protein identification using MS is an important technique in proteomics as well as a major generator of proteomics data. We have designed the protein identification data object model (PDOM) and developed a parser based on this model to facilitate the analysis and storage of these data. The parser works with HTML or XML files saved or exported from MASCOT MS/MS ions search in peptide summary report or MASCOT PMF search in protein summary report. The program creates PDOM objects, eliminates redundancy in the input file, and has the capability to output any PDOM object to a relational database. This program facilitates additional analysis of MASCOT search results and aids the storage of protein identification information. The implementation is extensible and can serve as a template to develop parsers for other search engines. The parser can be used as a stand-alone application or can be driven by other Java programs. It is currently being used as the front end for a system that loads HTML and XML result files of MASCOT searches into a relational database. The source code is freely available at http://www.ccbm.jhu.edu and the program uses only free and open-source Java libraries.

Databases, Protein↗

Proteome informatics I: bioinformatics tools for processing experimental data.

Bioinformatics tools for proteomics, also called proteome informatics tools, span today a large panel of very diverse applications ranging from simple tools to compare protein amino acid compositions to sophisticated software for large-scale protein structure determination. This review considers the available and ready to use tools that can help end-users to interpret, validate and generate biological information from their experimental data. It concentrates on bioinformatics tools for 2-DE analysis, for LC followed by MS analysis, for protein identification by PMF, by peptide fragment fingerprinting and by de novo sequencing and for data quantitation with MS data. It also discloses initiatives that propose to automate the processes of MS analysis and enhance the quality of the obtained results.

Algorithms↗

Proteome informatics II: bioinformatics for comparative proteomics.

The present review attempts to cover the most recent initiatives directed towards representing, storing, displaying and processing protein-related data suited to undertake "comparative proteomics" studies. Data interpretation is brought into focus. Efforts invested into analysing and interpreting experimental data increasingly express the need for adding meaning. This trend is perceptible in work dedicated to determining ontologies, modelling interaction networks, etc. In parallel, technical advances in computer science are spurred by the development of the Web and the growing need to channel and understand massive volumes of data. Biology benefits from these advances as an application of choice for many generic solutions. Some examples of bioinformatics solutions are discussed and directions for on-going and future work conclude the review.

Algorithms↗

Analysis of sequence requirements for protein tyrosine sulfation.

We analyzed sequences surrounding known tyrosine sulfation sites to determine the characteristics that distinguish these sites from those that do not undergo sulfation. Tests evaluated the number and position of acidic, basic, hydrophobic, and small amino acids, as well as disulfide and N-glycosylation (sugar) sites. We determined that composition-based tests that select close to 100% of known tyrosine sulfation sites reject 97% of the non-sulfated tyrosines. The acidic test, by far the most selective, eliminated 95% of the non-sulfated tyrosine residues and none of the sulfated tyrosines. Including the basic, hydrophobic, and disulfide tests increased the elimination rate to 97%. Whereas no position flanking the tyrosine residues had the same amino acid always present, imperfectly conserved amino acids found in some positions will improve the specificity of the tests.

Amino Acid Sequence↗

MOLE: a data management application based on a protein production data model.

MOLE (mining, organizing, and logging experiments) has been developed to meet the growing data management and target tracking needs of molecular biologists and protein crystallographers. The prototype reported here will become a Laboratory Information Management System (LIMS) to help protein scientists manage the large amounts of laboratory data being generated due to the acceleration in proteome research and will furthermore facilitate collaborations between groups based at different sites. To achieve this, MOLE is based on the data model for protein production devised at the European Bioinformatics Institute (Pajon A, et al., Proteins in press).

Algorithms↗

Comparing protein-ligand docking programs is difficult.

There is currently great interest in comparing protein-ligand docking programs. A review of recent comparisons shows that it is difficult to draw conclusions of general applicability. Statistical hypothesis testing is required to ensure that differences in pose-prediction success rates and enrichment rates are significant. Numerical measures such as root-mean-square deviation need careful interpretation and may profitably be supplemented by interaction-based measures and visual inspection of dockings. Test sets must be of appropriate diversity and of good experimental reliability. The effects of crystal-packing interactions may be important. The method used for generating starting ligand geometries and positions may have an appreciable effect on docking results. For fair comparison, programs must be given search problems of equal complexity (e.g. binding-site regions of the same size) and approximately equal time in which to solve them. Comparisons based on rescoring require local optimization of the ligand in the space of the new objective function. Re-implementations of published scoring functions may give significantly different results from the originals. Ostensibly minor details in methodology may have a profound influence on headline success rates.

Algorithms↗

Training wh-question production in agrammatic aphasia: analysis of argument and adjunct movement.

The present research utilized aspects of the Principles and Parameters Approach (P&PA; Chomsky, 1991, 1993) in linguistic theory as well as findings from the psycholinguistic literature as a basis for examining sentence production in aphasic individuals. We examined the production of particular wh-movement constructions--wh-questions requiring movement of an argument noun phrase (i.e., who and what questions) and those which require adjunct movement (i.e., when and where questions). Using a single-subject experimental treatment paradigm, subjects were sequentially trained to produce these wh-questions and, throughout training, generalization to untrained wh-questions relying on similar wh-movement processes was tested. As well, the influence of training on aspects of narrative and conversational discourse was examined. Seven agrammatic aphasic subjects who evinced difficulty producing (and comprehending) "complex" sentences (e.g., passives, object relative clauses, wh-questions)--sentences that involve movement of noun phrases (NPs) out of their canonical positions, leaving behind a "trace" of that movement or "gap"--participated in the study. Subjects were trained to produce wh-questions by taking them through a series of steps emphasizing the lexical and syntactic properties (e.g., thematic role assignment, movement processes, and proper selection of wh-morpheme) of declarative sentence counterparts of target sentences. Results revealed improved sentence production abilities in all subjects under study in both constrained sentence production and, importantly, in discourse tasks. The argument/adjunct distinction was observed in the sentence production recovery patterns noted in six of the seven subjects. Three of the subjects evinced correct argument movement across trained and untrained question structures when wh-questions relying on argument movement were trained; similarly, for these subjects, training structures relying of adjunct movement resulted in improved adjunct movement. Three of the remaining four subjects who required additional treatment to alleviate their wh-morpheme selection deficits, too showed covariance between argument and adjunct movement structures with each type of movement emerging across structures in temporal sequence. We discuss these data in terms of the operations necessary to produce wh-questions, the importance of considering linguistic and psycholinguistic data when designing treatment programs for language disordered patients, and the contribution that detailed recovery data can make both to understanding the nature of sentence production deficits and to issues regarding normal sentence production.

Adult↗

AFNI: software for analysis and visualization of functional magnetic resonance neuroimages.

A package of computer programs for analysis and visualization of three-dimensional human brain functional magnetic resonance imaging (FMRI) results is described. The software can color overlay neural activation maps onto higher resolution anatomical scans. Slices in each cardinal plane can be viewed simultaneously. Manual placement of markers on anatomical landmarks allows transformation of anatomical and functional scans into stereotaxic (Talairach-Tournoux) coordinates. The techniques for automatically generating transformed functional data sets from manually labeled anatomical data sets are described. Facilities are provided for several types of statistical analyses of multiple 3D functional data sets. The programs are written in ANSI C and Motif 1.2 to run on Unix workstations.

Brain↗

Incorporation of the Arden Syntax within the reimplementation of a closed-loop decision support system.

The initial implementation of a clinical decision support system, although extremely successful and popular with users, suffered from response time and operational support difficulties. As part of the redesign of the system, which uses closed-loop rules to propose laboratory and other investigations, the decision was taken to move to Arden Syntax for the expression of such rules, although in some areas the current standard was felt to be either inadequate or inelegant. Such limitations have been overcome by the development of local extensions to the Arden Syntax, which are described and where appropriate proposed as possible enhancements of the standard. The use of common UNIX tools in the creation of a compiler which converts Arden Medical Logic Modules to M (MUMPS) code is also discussed.

Decision Making, Computer-Assisted↗

Concept locator: a client-server application for retrieval of UMLS metathesaurus concepts through complex boolean query.

Concept Locator (CL) is a client-server application that accesses a Sybase relational database server containing a subset of the UMLS Metathesaurus for the purpose of retrieval of concepts corresponding to one or more query expressions supplied to it. CL's query grammar permits complex Boolean expressions, wildcard patterns, and parenthesized (nested) subexpressions. CL translates the query expressions supplied to it into one or more SQL statements that actually perform the retrieval. The generated SQL is optimized by the client to take advantage of the strengths of the server's query optimizer, and sidesteps its weaknesses, so that execution is reasonably efficient.

Database Management Systems↗