Matchmaker Exchange: finding genetic causes for rare diseases
The recent introduction of exome and genome sequencing into medical practice undoubtfully spead up solving monogenic “Mendelian” disorders. But a large fraction of patients with rare diseases still remain without a diganosis.
Very often, a patient has a suspicious mutations in a candidate gene but the absence of other known patiens with a similar clinical picture and the same mutations makes it impossible to valiadate the hypothesis. In such cases, finding just a single additional case with a deleterious mutation in the same gene may enable a diagnosis for the patient.
In many cases, people learn about these additional cases by pure chance: it is either by word of mouth between colleagues or by using social media. In a world of rapidly evolving information technologies, however, a more efficient solution is needed.
Several independent projects were started at different times to address this problem and gave rise to the platforms that use genotype- and phenotype-driven matching algorithms to find the cases with similar clinical picture and mutation patterns. These include: Gene Matcher, Genome Connect, LOVD, Cafe variome, DECIPHER, Undiagnosed Diseases Network, Broad RDAP, GENESIS Project, Phenome Central, Monarch Initiative, RD-connect, and PEER (Fig. 1)
Fig. 1 Databases and programs that gathered to form the basis for the MME.
Before the Matchmaker Exchange (MME), there were no attempts to organise these multiple disconnected projects in a system to facilitate the interaction between them.
To unify these efforts and harness the collective data across all of the databases, groups representing rare disease repositories held a meeting in October 2013 to launch an open collaboration later named the MME. This collaborative effort has launched a federated platform (exchange) to facilitate the identification of cases with similar phenotypic and genotypic profiles (matchmaking) through a standardized application programming interface (API) and procedural conventions. The MME enables searches of multiple databases (matchmaker services) from another, connected matchmaker service, without having to separately query all services, or deposit data in each one.
These steps have resulted in the current status of the MME in which three of the participating databases, Phenome Central, Gene Matcher, and DECIPHER, are now capable of returning the results of queries from API-supported connections to other MME services.
The MME has been identified as a demonstration project for the Global Alliance for Genomics and Health (GA4GH) and has been leveraging the expertise of the GA4GH working groups for guidance on pertinent aspects of the project.
This recent issue of the Human Mutation journal is dedicated to MME and contains detailed information about each project.