Introduction
To understand the disease relationships for all genes and variants in the Mendelian genome is nothing short of a grand challenge that represents, and will continue to represent, decades of scientific discovery. The Online Mendelian Inheritance in Man (OMIM) catalog lists 4,224 genes implicated in single gene disorders and traits (omim.org, accessed 3/4/22), yet estimates suggest more than 10,000 genes are likely to be found causal for monogenic disease (Bamshad et al., 2019) and typical diagnostic rates for individuals with suspected genetic disease are only around 25% (100,000 Genomes Project Pilot Investigators et al., 2021) . Much more variant-gene-disease discovery remains to be accomplished. As we continue to study increasingly rare Mendelian diseases, the need for responsible data sharing becomes even greater. A key driver of gene-disease discovery for rare disease is the ability to connect two or more parties looking for rare disease cases with the same candidate gene and an overlapping phenotype to expedite the gene-discovery process. This approach has been referred to as two-sided genome matchmaking and is the predominant use case for the Matchmaker Exchange (MME) (Figure 1 )(Philippakis et al., 2015) .
The MME consortium was formed in 2013 as a collaborative effort to launch a federated platform to enable two-sided genomic matchmaking through a standardized application programming interface (API) and procedural conventions. While the practice of matchmaking was already occurring within individual databases before the launch of MME, the data was siloed within each node. The MME network set out to connect databases into a federated network, something that had never been done before. The federated MME network launched in 2015 and the work to launch MME was described in detail by Philippakis and colleagues(Philippakis et al., 2015) , including formation of a steering committee and developing MME policies and approaches to queries and notifications. The federated MME network API enables exchange of information between the matchmakers through a set of required elements (https://github.com/ga4gh/mme-apis). This API is described (Buske, Schiettecatte, et al., 2015) , and was developed in collaboration with members of the Global Alliance for Genomics and Health (GA4GH)(Rehm et al., 2021) and the International Rare Diseases Research Consortium (IRDiRC) (Boycott et al., 2017) to ensure interoperability with other genomic services. This early work was described in a special issue of Human Mutation in 2015, The Matchmaker Exchange, which also included papers describing individual matchmaking services (Buske, Girdea, et al., 2015; Chatzimichali et al., 2015; Gonzalez et al., 2015; Kirkpatrick et al., 2015; Lancaster et al., 2015; Mungall et al., 2015; Sobreira et al., 2015) , case reports from clinicians, laboratories and researchers describing novel gene discoveries facilitated by genomic matchmaking (Au et al., 2015; Jurgens et al., 2015; Loucks et al., 2015) as well as other relevant topics (Akle et al., 2015; Brownstein et al., 2015; Krawitz et al., 2015; Lambertson et al., 2015) . Seven years later, we now report on the progress of the MME and advances in the field of genomic matchmaking in this special issue.