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A development environment for knowledge-based medical applications on the World-Wide Web.

The World-Wide Web (WWW) is increasingly being used as a platform to develop distributed applications, particularly in contexts, such as medical ones, where high usability and availability are required. In this paper we propose a methodology for the development of knowledge-based medical applications on the web, based on the use of an explicit domain ontology to automatically generate parts of the system. We describe a development environment, centred on the LISPWEB Common Lisp HTTP server, that supports this methodology, and we show how it facilitates the creation of complex web-based applications, by overcoming the limitations that normally affect the adequacy of the web for this purpose. Finally, we present an outline of a system for the management of diabetic patients built using the LISPWEB environment.

Artificial Intelligence↗

A web services choreography scenario for interoperating bioinformatics applications.

BACKGROUND: Very often genome-wide data analysis requires the interoperation of multiple databases and analytic tools. A large number of genome databases and bioinformatics applications are available through the web, but it is difficult to automate interoperation because: 1) the platforms on which the applications run are heterogeneous, 2) their web interface is not machine-friendly, 3) they use a non-standard format for data input and output, 4) they do not exploit standards to define application interface and message exchange, and 5) existing protocols for remote messaging are often not firewall-friendly. To overcome these issues, web services have emerged as a standard XML-based model for message exchange between heterogeneous applications. Web services engines have been developed to manage the configuration and execution of a web services workflow. RESULTS: To demonstrate the benefit of using web services over traditional web interfaces, we compare the two implementations of HAPI, a gene expression analysis utility developed by the University of California San Diego (UCSD) that allows visual characterization of groups or clusters of genes based on the biomedical literature. This utility takes a set of microarray spot IDs as input and outputs a hierarchy of MeSH Keywords that correlates to the input and is grouped by Medical Subject Heading (MeSH) category. While the HTML output is easy for humans to visualize, it is difficult for computer applications to interpret semantically. To facilitate the capability of machine processing, we have created a workflow of three web services that replicates the HAPI functionality. These web services use document-style messages, which means that messages are encoded in an XML-based format. We compared three approaches to the implementation of an XML-based workflow: a hard coded Java application, Collaxa BPEL Server and Taverna Workbench. The Java program functions as a web services engine and interoperates with these web services using a web services choreography language (BPEL4WS). CONCLUSION: While it is relatively straightforward to implement and publish web services, the use of web services choreography engines is still in its infancy. However, industry-wide support and push for web services standards is quickly increasing the chance of success in using web services to unify heterogeneous bioinformatics applications. Due to the immaturity of currently available web services engines, it is still most practical to implement a simple, ad-hoc XML-based workflow by hard coding the workflow as a Java application. For advanced web service users the Collaxa BPEL engine facilitates a configuration and management environment that can fully handle XML-based workflow.

Computational Biology↗

Special considerations for WEB-based clinical database applications.

The Hospital Information System at the University of Missouri-Columbia Veterinary Medical Teaching Hospital is implementing a web-based interface to the existing Hospital Information System. The "stateless" nature of HTML forms introduces a number of special considerations that, though not immediately obvious, nevertheless apply to any multi-user database application. Problems including identifying sessions and users, dealing with abandoned sessions or use of the "Back" arrow on the browser, record locking across multiple forms, state variables, and flow through "utility" forms. General solutions to each of these problems have been devised and are presented here.

Animals↗

eLearning in education and advanced training in neuroradiology: introduction of a web-based teaching and learning application.

INTRODUCTION: New information technologies offer the possibility of major improvements in the professional education and advanced training of physicians. The web-based, multimedia teaching and learning application Schoolbook has been created and utilized for neuroradiology. METHODS: Schoolbook is technically based as a content management system and is realized in a LAMP environment. The content is generated with the help of the developed system and stored in a database. The layout is defined by a PHP application, and the webpages are generated from the system. RESULTS: Schoolbook is realized as an authoring tool so that it can be integrated into daily practice. This enables the teacher to autonomously process the content into the web-based application which is used for lectures, seminars and self-study. A multimedia case library is the central building block of Schoolbook for neuroradiology, whereby the learner is provided with original diagnostic and therapeutic data from numerous individual cases. The user can put individual emphasis on key learning points as there are various ways to work with the case histories. Besides the case-based way of teaching and learning, a systematically structured way of dealing with the content is available. CONCLUSION: eLearning offers various opportunities for teaching and learning in academic and scientific as well as in economic contexts. Web-based applications such as Schoolbook may be beneficial not only for basic university education but also for the realization of international educational programmes such as the European Master of Medical Science with a major in neuroradiology.

Computer-Assisted Instruction↗

Prediction of posttranslational modifications using intact-protein mass spectrometric data.

We present a Web-based application that uses whole-protein masses determined by mass spectrometry to identify putative co- and posttranslational proteolytic cleavages and chemical modifications. The protein cleavage and modification engine (PROCLAME) requires as input an intact mass measurement and a precursor identification based on peptide mass fingerprinting or tandem mass spectrometry. This approach predicts mass-modifying events using a depth-first tree search, bounded by a set of rules controlled by a custom-built fuzzy logic engine, to explore a large number of possible combinations of modifications accounting for the experimental mass. Candidates are saved during a search if they are within a user-specified instrument mass accuracy; the total number of possible candidates searched is based on a specified fuzzy cutoff score. Candidates are scored and ranked using a simple probabilistic model. There is generally not enough information in an intact mass measurement to determine a single unique protein characterization; however, the program provides utility by expediting the identification of sets of putative events consistent with the mass data and ranking them for further investigation. This approach uses a simple, intuitive rule base and lends itself to discovery of unannotated posttranslational events. We have assessed the program with both in silico-generated test data and with published data from an analysis of large ribosomal subunit proteins, both from the yeast S. cerevisiae. Results indicate a high degree of sensitivity and specificity in characterizing proteins whose masses resulted from reasonable proteolysis and covalent modification scenarios. The application is available on the web at http://proclame.unc.edu.

Computational Biology↗

WebDietAID: an interactive Web-based nutritional counselor.

WebDietAID is a Web-based system aimed at assisting individuals affected by high serum cholesterol. The system tries to reproduce the types of intervention performed by a nutritional counselor. It is structured as a set of advisors, each of which handles a different side of the counseling process. The tasks of the advisors range from monitoring weight, to teaching about healthy nutrition, to assessing motivation and psychological obstacles to behavior change. WebDietAID is based on a development environment for Web-based applications that includes a dynamical Web server, a knowledge base management system, and an interface to a relational database. We describe the architecture of the system, and several of the implemented advisors. Finally, we discuss how the architecture could be generalized to other counseling domains.

Computer-Assisted Instruction↗

Using Web technologies for implementing testing strategies.

Although the application of Web technologies to laboratory services is relatively new, it is evolving rapidly and presents both promises and challenges to those adopting it for test strategy deployment. Its application can be helpful in disseminating information about a testing strategy once it is formulated, but it's more important potential contribution is in facilitating clinicians' use of the strategy. There is an array of ways Web technologies can be used to facilitate both the initiation of a strategy at the point of order entry and ensuring optimal use of the laboratory results that emanate from a testing strategy. Web technologies present a rich set of tools for those dedicated to enhancing the value of the laboratory's contribution to patient care.

Clinical Laboratory Information Systems↗

SOP3v2: web-based selection of oligonucleotide primer trios for genotyping of human and mouse polymorphisms.

SOP3v2 is a database-driven graphical web-based application for facilitating genotyping assay design. SOP3v2 accepts data input in numerous forms, including gene names, reference sequence numbers and physical location. For each entry, the application presents a set of recommended forward and reverse PCR primers, along with a sequencing primer, which is optimized for sequence-based genotyping assays. SOP3v2-generated oligonucleotide primer trios enable analysis of single nucleotide polymorphisms (SNPs) as well as insertion/deletion polymorphisms found in genomic DNA. The application's database was generated by warehousing information from the National Center for Biotechnology Information (NCBI) dbSNP database, genomic DNA sequences from human and mouse, and LocusLink gene attribute information. Query results can be sorted by their biological relevance, such as nonsynonymous coding changes or physical location. Human polymorphism queries may specify ethnicity, haplotype and validation status. Primers are developed using SOP3v2's core algorithm for evaluating primer candidates through stability tests and are suitable for use with sequence-based genotyping methods requiring locus-specific amplification. The method has undergone laboratory validation. Of the SOP3v2-designed primer trios that were tested, a majority (>80%) have successfully produced genotyping data. The application may be accessed via the web at http://imgen.ccbb.pitt.edu/sop3v2.

Animals↗

Integrating Application Programs for Bioinformatics Using a Web Browser.

We have constructed a general framework for integrating application programs with control through a local Web browser. This method is based on a simple inter-process message function from an external process to application programs. Commands to a target program are prepared in a script file, which is parsed by a message dispatcher program. When it is used as a helper application to a Web browser, these messages will be sent from the browser by clicking a hyper-link in a Web document. Our framework also supports pluggable extension-modules for application programs by means of dynamic linking. A prototype system is implemented on our molecular structure-viewer program, MOSBY. It successfully featured a function to load an extension-module required for the docking study of molecular fragments from a Web page. Our simple framework facilitates the concise configuration of Web softwares without complicated knowledge on network computation and security issues. It is also applicable for a wide range of network computations processing private data using a Web browser.

Journal Article↗

Developing a web-based data mining application to impact community health improvement initiatives: the Virginia Atlas of Community Health.

This article describes how a team from the Virginia Department of Health (VDH) and the Virginia Center for Healthy Communities (VCHC) attended the UNC Management Academy for Public Health to learn skills to address Virginia's commitment to using technology to improve the public's health. After creating a business plan for a food-safety information Web site, team members used that experience as well as Management Academy training in information technology, the management of data and finances, and strategic partnering to create a comprehensive tool with which to place customizable population data in the hands of anyone interested in pursuing population health improvement. The Virginia Atlas of Community Health, launched through the VCHC in 2003, places clear, compelling data in the hands of those who can influence decisions at the local level and create the most impact for health. Since the program's inception, more than 2,000 individuals have registered as ongoing users of the Virginia Atlas. Initially funded by a Turning Point grant from the Robert Wood Johnson Foundation, the program is sustained through a series of smaller grants and funding from the VDH.

Atlases as Topic↗

Personal health care services through digital television.

Personal health care has obtained increasing importance in the field of health care as the populations' age in the industrialised countries and resources available for health care remain limited. Personal health care through digital television is an exiting possibility in the realisation of new types of services answering to this demand for increased personal action and responsibility in health care. The possibilities of digital television in health care are studied in the Health Care Television (HCTV) research project of the Digital Media Institute at Tampere University of Technology. In this paper personal health care services are studied mainly from the perspective of the interactive service infrastructure of digital television. Firstly we present the general infrastructure of digital television and the different interactive service types of digital television. The usage of these service types in personal health care applications is also discussed. Finally, a web-based application based on chronic atrial fibrillation and its test use is presented. The application is used as a research platform for personal health care applications in digital television.

Anticoagulants↗

Biosphere: the interoperation of web services in microarray cluster analysis.

UNLABELLED: The growing use of DNA microarrays in biomedical research has led to the proliferation of analysis tools. These software programs address different aspects of analysis (e.g. normalisation and clustering within and across individual arrays) as well as extended analysis methods (e.g. clustering, annotation and mining of multiple datasets). Therefore, microarray data analysis typically requires the interoperability of multiple software programs involving different analysis types and methods. Such interoperation is often hampered by the heterogeneity inherent in the software tools (which may function by implementing different interfaces and using different programming languages). To address this problem, we employed the simple object access protocol (SOAP)-based web service approach that provides a uniform programmatic interface to these heterogeneous software components. To demonstrate this approach in the microarray context, we created a web server application, Biosphere, which interoperates a number of web services that are geographically widely distributed. These web services include a clustering web service, which is a suite of different clustering algorithms for analysing microarray data; XEMBL, developed at the European Bioinformatics Institute (EBI) for retrieving EMBL Nucleotide Sequence Database sequence data; and three gene annotation web services: GetGO, GetHAPI and GetUMLS. GetGO allows retrieval of Gene Ontology (GO) annotation, and the other two web services retrieve annotation from the biomedical literature that is indexed based on the Medical Subject Headings (MeSH) terms. With these web services, Biosphere allows the users to do the following: (i) cluster gene expression data using seven different algorithms; (ii) visualise the clustering results that are grouped statistically in colour; and (iii) retrieve sequence, annotation and citation data for the genes of interest. AVAILABILITY: Biosphere and its web services described in Web Service Description Language (WSDL) can be accessed at http://rook.cecid.hku.hk:8280/BiosphereServer.

Cluster Analysis↗

An Internet-based nuclear medicine teaching file.

UNLABELLED: Teaching file cases play an important role in the training of nuclear medicine residents; however, film-based teaching files have limitations, such as difficulty in accessing cases in a department with several remote clinical sites. The goal of this project was to develop a digital teaching file with the capability for local and remote (Internet) network access, with the additional requirements that viewing existing cases and addition of new cases be easy and simple. METHODS: The teaching file software (TF-Web) utilizes applications developed for the World-Wide-Web in combination with locally developed programs for importing images, entering case information, indexing, searching, case selection and case editing. The time required to add cases to the TF-Web and to access existing cases from local and remote network sites as well as computer storage requirements were assessed. RESULTS: Cases entered in TF-Web may be viewed either with or without diagnoses and may be accessed with acceptable speed (2-14 sec) from both local and remote network sites. A relatively complex case required 1.2 megabytes of storage, with lesser storage requirements for simpler cases. CONCLUSION: A digital teaching file has been developed that allows easy access from computers located both locally and elsewhere on the Internet. Digital storage requirements are reasonable, and, because of the unique nature of TF-Web, case storage may be distributed among multiple institutions.

Computer Communication Networks↗

PathMAPA: a tool for displaying gene expression and performing statistical tests on metabolic pathways at multiple levels for Arabidopsis.

BACKGROUND: To date, many genomic and pathway-related tools and databases have been developed to analyze microarray data. In published web-based applications to date, however, complex pathways have been displayed with static image files that may not be up-to-date or are time-consuming to rebuild. In addition, gene expression analyses focus on individual probes and genes with little or no consideration of pathways. These approaches reveal little information about pathways that are key to a full understanding of the building blocks of biological systems. Therefore, there is a need to provide useful tools that can generate pathways without manually building images and allow gene expression data to be integrated and analyzed at pathway levels for such experimental organisms as Arabidopsis. RESULTS: We have developed PathMAPA, a web-based application written in Java that can be easily accessed over the Internet. An Oracle database is used to store, query, and manipulate the large amounts of data that are involved. PathMAPA allows its users to (i) upload and populate microarray data into a database; (ii) integrate gene expression with enzymes of the pathways; (iii) generate pathway diagrams without building image files manually; (iv) visualize gene expressions for each pathway at enzyme, locus, and probe levels; and (v) perform statistical tests at pathway, enzyme and gene levels. PathMAPA can be used to examine Arabidopsis thaliana gene expression patterns associated with metabolic pathways. CONCLUSION: PathMAPA provides two unique features for the gene expression analysis of Arabidopsis thaliana: (i) automatic generation of pathways associated with gene expression and (ii) statistical tests at pathway level. The first feature allows for the periodical updating of genomic data for pathways, while the second feature can provide insight into how treatments affect relevant pathways for the selected experiment(s).

Arabidopsis↗

Three-dimensional computer graphics for surgical procedure learning: Web three-dimensional application for cleft lip repair.

OBJECTIVE: In surgical procedures for cleft lip, surgeons attempt to use various skin incisions and small flaps to achieve a better and more natural shape postoperatively. They must understand the three-dimensional (3D) structure of the lips. However, they may have difficulty learning the surgical procedures precisely from normal textbooks with two-dimensional illustrations. Recent developments in 3D computed tomography (3D-CT) and laser stereolithography have enabled surgeons to visualize the structures of cleft lips from desired viewpoints. However, this method cannot reflect the advantages offered by specific surgical procedures. To solve this problem, we used the benefits offered by 3D computer graphics (3D-CG) and 3D animation. DESIGN AND RESULTS: By using scanning 3D-CT image data of patients with cleft lips, 3D-CG models of the cleft lips were created. Several animations for surgical procedures such as incision designs, rotation of small skin flaps, and sutures were made. This system can recognize the details of an operation procedure clearly from any viewpoint, which cannot be acquired from the usual textbook illustrations. This animation system can be used for developing new skin-flap design, understanding the operational procedure, and using tools in case presentations. The 3D animations can also be uploaded to the World Wide Web for use in teleconferencing.

Cleft Lip↗

Web-based electronic patient records for collaborative medical applications.

We developed a web-based system to interactively display electronic patient records (EPR), such as DICOM images, graphics, and structure reports and therapy records, for intranet and internet collaborative medical applications. This system has three major components, a C/S (client/server) architecture for EPR data acquisition and authoring, and a Web B/S architecture for data delivering. The Web viewer of this system integrates multi-media display modules and remote control module together to provide interactive EPR display and manipulation functions for collaborative applications. We have successfully used this system two times to provide teleconsultation for severe acute respiratory syndrome (SARS) patients in Shanghai Infection Hospital and Xinhua Hospital. During the consultation, both the physicians in infection control area and the experts outside the control area could use this system interactively to manipulate and navigate the EPR objects of the SARS patients to facilitate a more precise diagnosis. This paper gives a new approach to create and manage image-based EPR from actual patient records, and also presents a novel method to use Web technology and DICOM standard to build an open architecture for collaborative medical applications. The system can be used for both intranet and internet medical applications such as tele-diagnosis, teleconsultation, and distant learning.

China↗

web-based interactive data processing: application to stable isotope metrology.

To address a fundamental need in stable isotope metrology, the National Institute of Standards and Technology (NIST) has established a web-based interactive data-processing system accessible through a common gateway interface (CGI) program on the internet site http://www. nist.gov/widps-co2. This is the first application of a web-based tool that improves the measurement traceability afforded by a series of NIST standard materials. Specifically, this tool promotes the proper usage of isotope reference materials (RMs) and improves the quality of reported data from extensive measurement networks. Through the International Atomic Energy Agency (IAEA), we have defined standard procedures for stable isotope measurement and data-processing, and have determined and applied consistent reference values for selected NIST and IAEA isotope RMs. Measurement data of samples and RMs are entered into specified fields on the web-based form. These data are submitted through the CGI program on a NIST Web server, where appropriate calculations are performed and results returned to the client. Several international laboratories have independently verified the accuracy of the procedures and algorithm for measurements of naturally occurring carbon-13 and oxygen-18 abundances and slightly enriched compositions up to approximately 150% relative to natural abundances. To conserve the use of the NIST RMs, users may determine value assignments for a secondary standard to be used in routine analysis. Users may also wish to validate proprietary algorithms embedded in their laboratory instrumentation, or specify the values of fundamental variables that are usually fixed in reduction algorithms to see the effect on the calculations. The results returned from the web-based tool are limited in quality only by the measurements themselves, and further value may be realized through the normalization function. When combined with stringent measurement protocols, two- to threefold improvements have been realized in the reproducibility of carbon-13 and oxygen-18 determinations across laboratories.

Journal Article↗

UpGene: Application of a web-based DNA codon optimization algorithm.

Although DNA codon optimization is a standard molecular biology strategy to overcome poor gene expression, to date no public software exists to facilitate this process. Among the uses of codon optimization, human immunodeficiency virus (HIV) vaccine development represents one of the most difficult challenges. A key obstacle to an effective DNA-based vaccine is the low-level expression of HIV genes in mammalian cells, which is due primarily to the instability of HIV mRNAs resulting from AU-rich elements and rare codon usage. In this report we describe the development of a DNA optimization algorithm integrated with a PCR primer design program to redesign specific coding sequences for maximal gene expression. Using this algorithm combination, together with PCR-based gene assembly, we have successfully optimized gene sequences for simian immunodeficiency virus (SIV) strain mac239 structural antigenic proteins gag and env, resulting in high-level gene expression in eukaryotic cells. Our findings demonstrate that our user-friendly algorithm is a valuable tool for DNA-based HIV vaccine development. Moreover, it can be used to optimize any other genes of interest and is freely available online at http://www.vectorcore.pitt.edu/upgene.html.

Algorithms↗