Bioinformatics Advance Access originally published online on January 19, 2007
Bioinformatics 2007 23(5):654-655; doi:10.1093/bioinformatics/btl675
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The ESID Online Database network
1Department of Rheumatology and Clinical Immunology, University Hospital Freiburg, Germany and 2Department of Clinical Immunology and Molecular Pathology, Royal Free Hospital, University College London, UK
*To whom correspondence should be addressed.
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ABSTRACT |
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 TOP ABSTRACT ACKNOWLEDGEMENTSREFERENCES |
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Summary: Primary immunodeficiencies (PIDs) belong to the group of rare diseases. The European Society for Immunodeficiencies (ESID), is establishing an innovative European patient and research database network for continuous long-term documentation of patients, in order to improve the diagnosis, classification, prognosis and therapy of PIDs. The ESID Online Database is a web-based system aimed at data storage, data entry, reporting and the import of pre-existing data sources in an enterprise business-to-business integration (B2B). The online database is based on Java 2 Enterprise System (J2EE) with high-standard security features, which comply with data protection laws and the demands of a modern research platform.
Availability: The ESID Online Database is accessible via the official website (http://www.esid.org/).
Contact: b.grimbacher{at}medsch.ucl.ac.uk
Supplementary information: Supplementary data are available at Bioinformatics online.
Primary immunodeficiencies (PIDs) are a group of rare diseases, which usually are the product of genetic defects of the immune system and its development. They represent a key area of study in immunology, providing a better understanding of the immunological pathways, their functions and development. To date, >100 different forms of PIDs have been identified to the molecular level (Shearer and Fischer, 2006). The main approach of identifying the genetic defect, is generating abundant and complex data from different sources, such as knockout mice experiments, genetic diagnosis and case reports. This information is mainly deposited and annotated in peer-reviewed databases, such as OMIM (http://www.ncbi.nlm.nih.gov/omim). While these databases offer a good description of the molecular defect, the correlation with the clinical phenotype is usually poor and limited only to specific case reports. In addition, the clinical phenotype resulting from a given genotype can be quite variable, depending upon many heterogeneous factors. Thus, this relation between genetic and clinical phenotype cannot be assumed to be linear, but is instead a complex expression of molecular defects regulated by endogenous and exogenous factors, which can lead to a complex set of phenotypic features (Buckley, 2005). This overall complexity can be addressed by filling in the existing gap in the clinical phenotype information for PIDs. Given the complexity and low prevalence of PIDs, only through transnational collaborations can sufficient patient numbers be obtained to perform adequate research. The European Society for Immunodeficiencies (ESID), which is a non-profit organization facilitating research on PIDs, has established a European patient and research database network for continuous long-term documentation of patients in order to provide a good platform for scientific research, filling the gap between the generated fundamental knowledge on PIDs and the actual healthcare services delivered to the patients. This secure database network, which is compliant with data protection and international ethics requirements, comprises several novel features and standards for clinical research databases.
The ESID Online Database consists of 206 disease-specific registries. The complete set of registries share a common dataset, which is called ‘Core Dataset’, handling non-identifying basic patient data, diagnosis, quality of life, therapy, transplantation and laboratory information. In addition to the ‘Core Dataset’, extended disease-specific datasets are being continuously developed. To date 30 registries include disease-specific extended datasets. The additional information provided by these extended datasets comprise among others aetiology, genetic cause, infection history, additional diagnoses, collected samples, biopsies and surgery events, clinical and additional investigation analyses.
The components of the system used by the ESID Online Database aim at data storage, data entry, reporting and the integration of pre-existing data sources within an enterprise business-to-business integration (B2B) based on Java 2 Enterprise System (J2EE) [Supplementary Material, Fig. 1]. For the data storage component, MySQL MaxDBTM(http://www.mysql.com/products/maxdb/) is used. The access to the database is carried out using a Java Database Connectivity interface, JDBCTM(http://java.sun.com/products/jdbc/). As J2EE application server, Sun JavaTMSystem Application Server (http://www.sun.com/software/products/appsrvr/index.xml) is used. The central component of the system is the Toolwerk Enterprise Integration and Development Platform Application (EIDP) (http://www.toolwerk.de/). EIDP is a multi-tier Java Enterprise Development Platform which provides XML programming interfaces to the different components of a J2EE system, i.e. web tier, EJB tier and services tier. As with the web interface, the EJB tier provides the developer with specific functionalities for accessing databases, services and legacy systems. It is even possible to connect different EIDPs together in order to develop complex, secure and high data protection standard systems. The services tier offers specific functionalities for developing the exchange of huge datasets. This tier infrastructure is based on the core of SOAP, but implements its own structures for batch processing. A service builder Java library is available for the development of the clients. The service tier uses the EIDP core system (EJB tier) to access the different data sources [Supplementary Material, Figs 2 and 3].
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The ESID Online Database can be accessed using a standard web browser. The access through web browsers is controlled through a user name and password combination. No additional technical prerequisites or plug-ins are required. Communication with other systems is either implemented via SOAP web services calling the EIDP services tier or proprietary communication models when required, where the source database can be accessed through the main EJB tier (plain JDBC, pool connections, other EIDPs or legacy systems) [Supplementary Material, Fig. 4]. All the B2B integration and normal end-user access is only implemented via SSL/TLS encryption. The central server of the ESID Online Database is physically hosted within the secure server network of the IT Centre of the University Hospital Freiburg, Germany.
All the registries within the ESID Online Database are managed through multiple entities [Supplementary Material, –7]. The complete set of entities is compliant with the PID list of the International Union of Immunological Societies (Notarangelo et al., 2006). With this entity separation, the patients and the data contained are specific to one disease and cannot be accessed through a different application entity. Despite this separation at the application level, the system uses one common database scheme [Supplementary Material, Fig. 5].
The ESID Online Database has an intuitive web interface. A series of web forms are accessible through a side menu containing patient-specific data, which is sorted according to dates where applicable, allowing the documentation of static and follow-up data (Fig. 1).
The ESID Online Database uses a complex and secure permission grant system, which regulates the access to the system resources. Every user is assigned at least a role which controls the display of contents and methods for querying the database. In addition, specific centre and sub-centre codes are also generated, filtering the list of patients available for querying and documenting.
The ESID Online Database also implements advanced logic for more specific tasks, e.g. charts and report generation, search modules, mutation validation, calculations, integration with external databases and elaborated data entry functionalities based on graphical representations. All this logic is implemented through Java code and integrated into the main application web tier as standard plain-old Java objects (POJO), providing a standard mechanism, based on servlets, to combine reusable pieces of Java classes with the session variables and the access to EJB resources [Supplementary Material, Fig. 6].
The use of ICD10 codes (http://www.who.int/classifications/icd/) for disease events descriptions and MeSH terms (available at http://www.nlm.nih.gov/mesh/) for organs and tissues, provides a good platform for the standardized characterization of PIDs, these terms and ontologies are integrated into the web interface, through search functions and forms [Supplementary Material, Fig. 7 and Table 8]. An integration with validated mutation data from the IDbases databases (Riikonen and Vihinen, 1999), is already being implemented, providing cross-linked information to other biological databases, such as Human Genome Database (http://www.gdb.org/gdb/), OMIM, EMBL (http://www.ebi.ac.uk/embl/) and UniProt-Swiss database (http://www.uniprot.org/).
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ACKNOWLEDGEMENTS |
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TOPABSTRACTACKNOWLEDGEMENTSREFERENCES |
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The ESID Online Database project is sponsored by companies of the Plasma Protein Therapeutics Association Europe (Baxter, Biotest, Grifols, Kedrion, Octapharma) and funded in part by the European Union, EU Contract SP23-CT-2005-006411, EURO-POLICY-PID.
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FOOTNOTES |
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Associate Editor: Charlie Hodgman
Received on July 19, 2006; revised on December 15, 2006; accepted on January 4, 2007
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REFERENCES |
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TOPABSTRACTACKNOWLEDGEMENTSREFERENCES |
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Buckley RH. Variable phenotypic expression of mutations in genes of the immune system. J. Clin. Invest. (2005) 115:2974–2976.[CrossRef][Web of Science][Medline]
Notarangelo L, et al, International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee. J. Allergy Clin. Immunol. (2006) 117. Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee Meeting in Budapest, 2005. 883–896.[CrossRef][Web of Science][Medline]
Riikonen P, Vihinen M. MUTbase: maintenance and analysis of distributed mutation databases. Bioinformatics (1999) 15:852–859.
Shearer WT, Fischer A. The last 80 years in primary immunodeficiency: how far have we come, how far need we go? J. Allergy Clin. Immunol. (2006) 117:748–752.[CrossRef][Web of Science][Medline]
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