A Web Server for the Standardization of Molecular Diagnosis of Huntington?s Disease in Latin America

ROHR, CRISTIAN OSCAR; DOPAZO, HERNAN JAVIER; PERANDONES, CLAUDIA

Rosario

Congreso; IV Argentinean Conference on Computational Biology and Bioinformatics & the IV Conference of the Iberoamerican Society for Bioinformatics (SOIBIO); 2013

A2B2C-SOIBIO

Background Huntington?́s disease (HD) is a midlife-onset disease, which strikes at a mean age of 40 years, but its onset may vary from 4 to 80 years of age [1, 2]. It is a progressive neurodegenerative disorder with primary neuro-pathological involvement of the basal ganglia. HD is invariably fatal, without periods of remission, and the course from onset to death averages 15 to 17 years. It is worth mentioning that the confirmatory diagnosis in HD is carried out by means of the determination of the number of CAG expansions in the htt gene [3]. This means that once diagnostic tests are conducted, and depending on their results, therapeutic strategies will be established and the identification of individuals at risk of suffering from the disease will be conducted, thus the relevance of the diagnostic determination from a medical, psychological and social point of view. Currently, in Argentina and other Latin American countries, HD diagnosis is not consistent with international standards due to economic and technological constraints [4]. The standardization of molecular diagnostics for HD in Latin America [5] will seek to: Bring the internationally-recognized standards for CAG predictive testing to Latin America. Develop a framework for validation that could be widely implemented in Latin American laboratories to improve the overall quality of the HD genetic testing services. At the same time, it should respect the need for flexibility imposed by regional requirements and regulations as well as practical constraints such as testing volumes and resources. Here we present a web-based server specifically designed to develop a feasibility study to be conducted in several testing facilities, in order to standardize the molecular diagnosis of HD in Latin America. Methods The site is hosted in a Ubuntu 13.04 web server running Apache 2.2.22 on a PC equipped with a Intel Core i7 CPU and 32GB of RAM. It was built in HTML and JavaScript on the client side and PHP 5.4.9 on the server side. To enhance user experience, for fronted functionality and styling Twitter Bootstrap was used as well as jQuery for interactive user interface operations. The data is stored in a MySQL 5.5.32 database. This constitutes a LAMP structure Linux-Apache-MySQL-PHP. The website was tested in Firefox, Chrome, Safari and Internet Explorer web browsers. Results The system is only accessible to registered users at participating sites. To ensure that they have the authority to proceed with data entry, authorized users are issued their own electronic signature, i.e., a username-password combination. Each user has an appropriate level of access to data, since the application supports different user roles. Security issues have been addressed during the development and deployment of the application. The web-server contains six (6) pages with a total of 150 questions specifically designed to cover key components of the molecular genetic testing process: analytical validation, clinical validation, clinical utility and considerations of the ethical, legal and social implications of the test. The subsequent analysis of results will be both of qualitative (enumeration of laboratory devices, description of internal operating procedures, facilities, environmental conditions, pre-analytical, analytical and post-analytical procedures and quality aspects) and quantitative variables (enumeration of laboratory devices, number of annual cases, laboratory personnel, etc). Conclusions It is now little over two decades since the identification of the gene for HD and its mutation; the advances that have occurred in our understanding of the disorder during this time have been truly profound. However, in Latin America, the molecular diagnosis of HD, which is an essential component for the planning of comprehensive and adequate services for patients and families, still remains an unsolved problem. This fact has led us to develop this web server, the results of which will be used to improve the available genetic testing facilities, which will be brought to international standards through training and validation testing. The successful implementation of this web server depends on the collaborative efforts of multiple institutions with expertise in neurodegenerative diseases, medical genetics and computer science. This database offers a number of benefits, including: 1) standardized data elements, vocabulary, and forms for data collection, 2) computerized audits and data quality control, 3) submission of data through the internet in an effective, secure, and easy-to-use way, and 4) the ability to exchange information with other registry systems. Although this database has been specifically designed for HD, the underlying information system is flexible and constitutes a model that could potentially be used for other diseases [6]. References 1. Hayden MR. Huntington's chorea. London: Springer; 1981. 2. Harper PS. Huntington's disease. Major problems in Neurology. Vol. 22: WB Saunders; 1991:31-72. 3. Gusella JF, MacDonald ME. Huntington's disease: CAG genetics expands neurobiology. Curr Opin Neurobiol. 1995;5(5):656-62. 4. Maciel RO, Cardoso FE, Chaná-Cuevas P, Cosentino C, Fernández W, Rieder CR, Serrano-Dueñas M, Weiser R. Care of patients with Huntington's disease in South America: a survey. Arq Neuropsiquiatr. 2013 Jun;71(6):368-70. 5. Mattocks CJ, Morris MA, Matthijs G, Swinnen E, Corveleyn A, Dequeker E, Müller CR, Pratt V, Wallace A. EuroGentest Validation Group. A standardized framework for the validation and verification of clinical molecular genetic tests. Eur J Hum Genet. 2010 Dec; 18(12):1276-88.