The Matchmaker Exchange: a platform for rare disease gene discovery

Abstract

There are few better examples of the need for data sharing than in the rare disease community, where patients, physicians, and researchers must search for "the needle in a haystack" to uncover rare, novel causes of disease within the genome. Impeding the pace of discovery has been the existence of many small siloed datasets within individual research or clinical laboratory databases and/or disease-specific organizations, hoping for serendipitous occasions when two distant investigators happen to learn they have a rare phenotype in common and can "match" these cases to build evidence for causality. However, serendipity has never proven to be a reliable or scalable approach in science. As such, the Matchmaker Exchange (MME) was launched to provide a robust and systematic approach to rare disease gene discovery through the creation of a federated network connecting databases of genotypes and rare phenotypes using a common application programming interface (API). The core building blocks of the MME have been defined and assembled. Three MME services have now been connected through the API and are available for community use. Additional databases that support internal matching are anticipated to join the MME network as it continues to grow.

Keywords: GA4GH, IRDiRC; Matchmaker Exchange; gene discovery; genomic API; matchmaking; rare disease.

Figure 1. Databases and programs that gathered to form the basis for the Matchmaker Exchange

The MME includes representatives from the founding organizations and databases supporting or intending to support matchmaking services (Tables 1 and 2). Collaborative work has focused on both the technical aspects of data sharing, as well as policy considerations. This work has resulted in version 1.0 of a MME API (Buske et al., 2015b, this issue), a set of requirements for qualifying as a MME service, and a user agreement for querying the MME. The MME has been identified as a demonstration project for the Global Alliance for Genomics and Health (GA4GH) and the MME has been leveraging the expertise of the GA4GH working groups for guidance on pertinent aspects of the project.

Figure 2. The current state of API-connected MME services

The figure depicts those databases that have implemented the Matchmaker Exchange API and satisfied the MME service requirements as described above. Additional databases are in the process of implementing the API and other MME service requirements. Progress can be monitored via the MME website (http://www.matchmakerexchange.org).