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Ontology annotation treebrowser : an interactive tool where the complementarity of medical subject headings and gene ontology improves the interpretation of gene lists.

Gene expression and proteomics analysis allow the investigation of thousands of biomolecules in parallel. This results in a long list of interesting genes or proteins and a list of annotation terms in the order of thousands. It is not a trivial task to understand such a gene list and it would require extensive efforts to bring together the overwhelming amounts of associated information from the literature and databases. Thus, it is evident that we need ways of condensing and filtering this information. An excellent way to represent knowledge is to use ontologies, where it is possible to group genes or terms with overlapping context, rather than studying one-dimensional lists of keywords. Therefore, we have built the ontology annotation treebrowser (OAT) to represent, condense, filter and summarise the knowledge associated with a list of genes or proteins. The OAT system consists of two disjointed parts; a MySQL database named OATdb, and a treebrowser engine that is implemented as a web interface. The OAT system is implemented using Perl scripts on an Apache web server and the gene, ontology and annotation data is stored in a relational MySQL database. In OAT, we have harmonized the two ontologies of medical subject headings (MeSH) and gene ontology (GO), to enable us to use knowledge both from the literature and the annotation projects in the same tool. OAT includes multiple gene identifier sets, which are merged internally in the OAT database. We have also generated novel MeSH annotations by mapping accession numbers to MEDLINE entries. The ontology browser OAT was created to facilitate the analysis of gene lists. It can be browsed dynamically, so that a scientist can interact with the data and govern the outcome. Test statistics show which branches are enriched. We also show that the two ontologies complement each other, with surprisingly low overlap, by mapping annotations to the Unified Medical Language System. We have developed a novel interactive annotation browser that is the first to incorporate both MeSH and GO for improved interpretation of gene lists. With OAT, we illustrate the benefits of combining MeSH and GO for understanding gene lists. OAT is available as a public web service at: http://www.ifm.liu.se/bioinfo/oat.

Algorithms↗

RIKEN mouse genome encyclopedia.

We have been working to establish the comprehensive mouse full-length cDNA collection and sequence database to cover as many genes as we can, named Riken mouse genome encyclopedia. Recently we are constructing higher-level annotation (Functional ANnoTation Of Mouse cDNA; FANTOM) not only with homology search based annotation but also with expression data profile, mapping information and protein-protein database. More than 1,000,000 clones prepared from 163 tissues were end-sequenced to classify into 159,789 clusters and 60,770 representative clones were fully sequenced. As a conclusion, the 60,770 sequences contained 33,409 unique. The next generation of life science is clearly based on all of the genome information and resources. Based on our cDNA clones we developed the additional system to explore gene function. We developed cDNA microarray system to print all of these cDNA clones, protein-protein interaction screening system, protein-DNA interaction screening system and so on. The integrated database of all the information is very useful not only for analysis of gene transcriptional network and for the connection of gene to phenotype to facilitate positional candidate approach. In this talk, the prospect of the application of these genome resourced should be discussed. More information is available at the web page: http://genome.gsc.riken.go.jp/.

Animals↗

An object-oriented programming system for the integration of internet-based bioinformatics resources.

The Internet consists of a vast inhomogeneous reservoir of data. Developing software that can integrate a wide variety of different data sources is a major challenge that must be addressed for the realisation of the full potential of the Internet as a scientific research tool. This article presents a semi-automated object-oriented programming system for integrating web-based resources. We demonstrate that the current Internet standards (HTML, CGI [common gateway interface], Java, etc.) can be exploited to develop a data retrieval system that scans existing web interfaces and then uses a set of rules to generate new Java code that can automatically retrieve data from the Web. The validity of the software has been demonstrated by testing it on several biological databases. We also examine the current limitations of the Internet and discuss the need for the development of universal standards for web-based data.

Computational Biology↗

Automated scheduling of radiologic procedures.

The dramatic advances in radiology have increased the number and type of machines and of daily performed exams. Consequently, workload and management organization problems have also markedly increased. Automated, computerized scheduling of radiologic exams is certainly a step forward in a modern rational management of a Diagnostic Imaging service: the relationship with the patient is improved with the optimization of care delivered and of the radiologist's work, who with the new technology is able to rapidly consult the previous exams as well as the list of exams to be performed. The advances in health care information technology imply communications at a distance. From each ward of the hospital, requests for radiologic exams can be automatically scheduled or kept on a dynamic waiting list for automated input in future work shifts. Via the same system, reports (and also radiologic images) can by rapidly transmitted to the wards. At the "Università Cattolica del S. Cuore" from several years, an integrated information system has been implemented for management of patient data, exams and care delivered. Radiology represents one of major departmental systems of the network for the number of machines installed and the amount of information supplied. The system will be soon able to store images from all digital and nondigital machines, and visualize on dedicated workstations the images of ongoing exams or stored previous ones.

Appointments and Schedules↗

GO::TermFinder--open source software for accessing Gene Ontology information and finding significantly enriched Gene Ontology terms associated with a list of genes.

SUMMARY: GO::TermFinder comprises a set of object-oriented Perl modules for accessing Gene Ontology (GO) information and evaluating and visualizing the collective annotation of a list of genes to GO terms. It can be used to draw conclusions from microarray and other biological data, calculating the statistical significance of each annotation. GO::TermFinder can be used on any system on which Perl can be run, either as a command line application, in single or batch mode, or as a web-based CGI script. AVAILABILITY: The full source code and documentation for GO::TermFinder are freely available from http://search.cpan.org/dist/GO-TermFinder/.

Abstracting and Indexing↗

A multi-resolution approach for content-based image retrieval on the Grid--application to breast cancer detection.

OBJECTIVES: Hospitals and medical centers are producing more and more data that need to be processed. Those data are confidential, heterogeneous, and limited to the geographic site where they have been produced. Unless properly anonymized, they cannot be distributed on wide area networks. METHODS: Grid technologies allow the globalization of storage and processing resources, and enable large-scale experimentations on distributed data. They constitute a promising tool to treat the different data and analyze the knowledge they contain, while offering secured access and high-performance computing capacities to the different users. Our aim is to evaluate the possibilities of grid technologies for handling medical data. RESULTS AND CONCLUSIONS: In this paper, we focus on a breast cancer diagnosis assistance tool, based on distributed and incremental knowledge construction and a content-based image retrieval system. We analyze the different scenarios of uses of such a tool. We further propose an algorithm that indexes mammographic images for content-based query purposes. This algorithm is tested on images of different resolutions in order to reduce the indexation time and we analyze its performance with experiments on the grid.

Algorithms↗

ASAP: automated sequence annotation pipeline for web-based updating of sequence information with a local dynamic database.

The automated sequence annotation pipeline (ASAP) is designed to ease routine investigation of new functional annotations on unknown sequences, such as expressed sequence tags (ESTs), through querying of web-accessible resources and maintenance of a local database. The system allows easy use of the output from one search as the input for a new search, as well as the filtering of results. The database is used to store formats and parameters and information for parsing data from web sites. The database permits easy updating of format information should a site modify the format of a query or of a returned web page.

Database Management Systems↗

GenomeDiagram: a python package for the visualization of large-scale genomic data.

UNLABELLED: We present GenomeDiagram, a flexible, open-source Python module for the visualization of large-scale genomic, comparative genomic and other data with reference to a single chromosome or other biological sequence. GenomeDiagram may be used to generate publication-quality vector graphics, rastered images and in-line streamed graphics for webpages. The package integrates with datatypes from the BioPython project, and is available for Windows, Linux and Mac OS X systems. AVAILABILITY: GenomeDiagram is freely available as source code (under GNU Public License) at http://bioinf.scri.ac.uk/lp/programs.html, and requires Python 2.3 or higher, and recent versions of the ReportLab and BioPython packages. SUPPLEMENTARY INFORMATION: A user manual, example code and images are available at http://bioinf.scri.ac.uk/lp/programs.html.

Chromosome Mapping↗

Stochastic clustering for organizing distributed information sources.

The number of information sources and the volumes of data in these information sources have greatly increased, which may be attributed to the ever-increasing complexity of real-world applications. The enormous amount of information available in the information sources in a distributed information-providing environment has created a need to provide users with tools to effectively and efficiently navigate and retrieve information. Queries in such an environment often access information from multiple information sources. This may be attributed to navigational characteristics. Clusters provide a structure for organizing the large number of information sources for efficient browsing, searching, and retrieval. This paper presents a stochastically-based clustering mechanism, called the Markov model mediator (MMM), to group the information sources into a set of useful clusters. Each information source cluster groups those information sources that show similarities in their data access behavior. Information sources within the same cluster are expected to be able to provide most of the required information among themselves for user queries that are closely related with respect to a particular application. This can significantly improve system response time, query performance, and result in an overall improvement in decision support. Empirical studies on real databases are performed and the results demonstrate that our proposed mechanism leads to a better set of clusters in comparison with other clustering methods. This serves to illustrate the effectiveness of our proposed MMM mechanism.

Artificial Intelligence↗

Development of an enhanced leg muscle rehabilitation system.

This paper aims to develop an enhanced rehabilitation and assessment system for people with impaired leg muscles, and for people who need to improve their leg muscle function. Through interactive design and real time evaluation, medical staff can totally control the training situation for patients and therefore provide a better training program, so that overall a better treatment performance can be achieved. The system consists of four major parts. Sensory and signal conversion circuits convert the lever arm lengths and muscle strengths of the leg into a proper electronic signal and then deliver this to the computer. Then, the intelligent and interactive interface design lets a trainee complete the training process independently without the involvement of medical staff. In addition, the trainee can see the training results at the end of the training process on the computer screen. The training protection and evaluation mechanism effectively monitors the training situation, based on the individual status settings by the medical staff, and thus any further impairment can be avoided. The database management system is developed to store related personal data, system settings and training results, which can then be retrieved for control and assessment. In comparison to similar equipment the proposed system demonstrates a much better performance, particularly in system functions, accuracy, operation and costs.

Equipment Design↗

The Ensembl Web site: mechanics of a genome browser.

The Ensembl Web site (http://www.ensembl.org/) is the principal user interface to the data of the Ensembl project, and currently serves >500,000 pages (approximately 2.5 million hits) per week, providing access to >80 GB (gigabyte) of data to users in more than 80 countries. Built atop an open-source platform comprising Apache/mod_perl and the MySQL relational database management system, it is modular, extensible, and freely available. It is being actively reused and extended in several different projects, and has been downloaded and installed in companies and academic institutions worldwide. Here, we describe some of the technical features of the site, with particular reference to its dynamic configuration that enables it to handle disparate data from multiple species.

Animals↗

Automated acquisition of rules from clinical databases and its evaluation.

This paper presents an approach to induction of rules from databases using rough set model. The system was evaluated on three clinical databases, and induced results were compared with other conventional rule induction methods and medical experts' rules. The results show that the introduced results outperforms other methods, but that the description length of induced rules is a little short, compared with that of experts' rules, which suggests that experts' rules are combination of different kinds of reasoning, rather than simple classification.

Algorithms↗

A distributed computation of Interpro Pfam, PROSITE and ProDom for protein annotation.

Interpro is a widely used tool for protein annotation in genome sequencing projects, demanding a large amount of computation and representing a huge time-consuming step. We present a strategy to execute programs using databases Pfam, PROSITE and ProDom of Interpro in a distributed environment using a Java-based messaging system. We developed a two-layer scheduling architecture of the distributed infrastructure. Then, we made experiments and analyzed the results. Our distributed system gave much better results than Interpro Pfam, PROSITE and ProDom running in a centralized platform. This approach seems to be appropriate and promising for highly demanding computational tools used for biological applications.

Computational Biology↗

K-SPMM: a database of murine spermatogenic promoters modules & motifs.

BACKGROUND: Understanding the regulatory processes that coordinate the cascade of gene expression leading to male gamete development has proven challenging. Research has been hindered in part by an incomplete picture of the regulatory elements that are both characteristic of and distinctive to the broad population of spermatogenically expressed genes. DESCRIPTION: K-SPMM, a database of murine Spermatogenic Promoters Modules and Motifs, has been developed as a web-based resource for the comparative analysis of promoter regions and their constituent elements in developing male germ cells. The system contains data on 7,551 genes and 11,715 putative promoter regions in Sertoli cells, spermatogonia, spermatocytes and spermatids. K-SPMM provides a detailed portrait of promoter site components, ranging from broad distributions of transcription factor binding sites to graphical illustrations of dimeric modules with respect to individual transcription start sites. Binding sites are identified through their similarities to position weight matrices catalogued in either the JASPAR or the TRANSFAC transcription factor archives. A flexible search function allows sub-populations of promoters to be identified on the basis of their presence in any of the four cell-types, their association with a list of genes or their component transcription-factor families. CONCLUSION: This system can now be used independently or in conjunction with other databases of gene expression as a powerful aid to research networks of co-regulation. We illustrate this with respect to the spermiogenically active protamine locus in which binding sites are predicted that align well with biologically foot-printed protein binding domains. AVAILABILITY: http://klab.med.wayne.edu/kspmm/

Amino Acid Motifs↗

DIG--a system for gene annotation and functional discovery.

SUMMARY: We describe a database and information discovery system named DIG (Duke Integrated Genomics) designed to facilitate the process of gene annotation and the discovery of functional context. The DIG system collects and organizes gene annotation and functional information, and includes tools that support an understanding of genes in a functional context by providing a framework for integrating and visualizing gene expression, protein interaction and literature-based interaction networks.

Chromosome Mapping↗

GARSA: genomic analysis resources for sequence annotation.

SUMMARY: Growth of genome data and analysis possibilities have brought new levels of difficulty for scientists to understand, integrate and deal with all this ever-increasing information. In this scenario, GARSA has been conceived aiming to facilitate the tasks of integrating, analyzing and presenting genomic information from several bioinformatics tools and genomic databases, in a flexible way. GARSA is a user-friendly web-based system designed to analyze genomic data in the context of a pipeline. EST and GGS data can be analyzed using the system since it accepts (1) chromatograms, (2) download of sequences from GenBank, (3) Fasta files stored locally or (4) a combination of all three. Quality evaluation of chromatograms, vector removing and clusterization are easily performed as part of the pipeline. A number of local and customizable Blast and CDD analyses can be performed as well as Interpro, complemented with phylogeny analyses. GARSA is being used for the analyses of Trypanosoma vivax (GSS and EST), Trypanosoma rangeli (GSS, EST and ORESTES), Bothrops jararaca (EST), Piaractus mesopotamicus (EST) and Lutzomyia longipalpis (EST). AVAILABILITY: The GARSA system is freely available under GPL license (http://www.biowebdb.org/garsa/). For download requests visit http://www.biowebdb.org/garsa/ or contact Dr Alberto Dávila.

Animals↗

Bioinformatics visualization and integration with open standards: the Bluejay genomic browser.

We have created a new Java-based integrated computational environment for the exploration of genomic data, called Bluejay. The system is capable of using almost any XML file related to genomic data. Non-XML data sources can be accessed via a proxy server. Bluejay has several features, which are new to Bioinformatics, including an unlimited semantic zoom capability, coupled with Scalable Vector Graphics (SVG) outputs; an implementation of the XLink standard, which features access to MAGPIE Genecards as well as any BioMOBY service accessible over the Internet; and the integration of gene chip analysis tools with the functional assignments. The system can be used as a signed web applet, Web Start, and a local stand-alone application, with or without connection to the Internet. It is available free of charge and as open source via http://bluejay.ucalgary.ca.

Computational Biology↗

Computational methods for the design of effective therapies against drug resistant HIV strains.

The development of drug resistance is a major obstacle to successful treatment of HIV infection. The extraordinary replication dynamics of HIV facilitates its escape from selective pressure exerted by the human immune system and by combination drug therapy. We have developed several computational methods whose combined use can support the design of optimal antiretroviral therapies based on viral genomic data.

Database Management Systems↗