Many patients suffering from Rare Disease harbour genomic variants (sequence variants or copy number variants) that by disrupting normal gene expression lead to disease. However, many variants are novel or extremely rare, making clinical interpretation problematic and genotype-phenotype correlations uncertain. Identification of patients sharing variants in a given gene and having phenotypic features in common leads to greater certainty in the pathogenic nature of the gene and enables to the role of novel genes in development and disease to be defined. Furthermore, analysis of the type of genomic variant and of its consequence (eg. Loss of function or gain of function) enables insight into the mechanism of disease and potential therapeutic targets.
DECIPHER is a web-based platform for secure deposition, analysis, and sharing of plausibly pathogenic genomic variants from well-phenotyped patients suffering from rare genetic disorders. DECIPHER aids clinical interpretation of these rare sequence and copy-number variants by providing tools for variant analysis and identification of other patients exhibiting similar genotype–phenotype characteristics. DECIPHER also provides mechanisms to encourage collaboration among a global community of clinical centers and researchers, as well as exchange of information between clinicians and researchers within a consortium, to accelerate discovery and diagnosis. DECIPHER has contributed to matchmaking efforts by enabling the global clinical genetics community to identify many previously undiagnosed syndromes and new disease genes, and has facilitated the publication of over 800 peer-reviewed scientific publications since 2004.
Contributing to the DECIPHER database is an international community of academic departments of clinical genetics and rare disease genomics now numbering more than 250 projects and having uploaded more than 19,000 cases. Each contributing centre has a nominated rare disease clinician or clinical geneticist who is responsible for overseeing data entry and membershipfor their centre. DECIPHER enables a flexible approach to data-sharing. Each project maintains control of its own patient data (which are password protected within the project’s own DECIPHER project) until consent is given to share the data with chosen parties in a collaborative group or to allow anonymous genomic and phenotypic data to become freely viewable. Once data are shared, consortium members are able to gain access to the patient report and contact each other to discuss patients of mutual interest.