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. 2017 Oct 18:95:9.31.1-9.31.15.
doi: 10.1002/cphg.50.

Matchmaker Exchange

Nara L M Sobreira  1 , Harindra Arachchi  2 , Orion J Buske  3 , Jessica X Chong  4 , Ben Hutton  5 , Julia Foreman  5 , François Schiettecatte  6 , Tudor Groza  7   8 , Julius O B Jacobsen  9 , Melissa A Haendel  10 , Kym M Boycott  11 , Ada Hamosh  12 , Heidi L Rehm  2 ; Matchmaker Exchange Consortium
Affiliations

Matchmaker Exchange

Nara L M Sobreira et al. Curr Protoc Hum Genet. .

Abstract

In well over half of the individuals with rare disease who undergo clinical or research next-generation sequencing, the responsible gene cannot be determined. Some reasons for this relatively low yield include unappreciated phenotypic heterogeneity; locus heterogeneity; somatic and germline mosaicism; variants of uncertain functional significance; technically inaccessible areas of the genome; incorrect mode of inheritance investigated; and inadequate communication between clinicians and basic scientists with knowledge of particular genes, proteins, or biological systems. To facilitate such communication and improve the search for patients or model organisms with similar phenotypes and variants in specific candidate genes, we have developed the Matchmaker Exchange (MME). MME was created to establish a federated network connecting databases of genomic and phenotypic data using a common application programming interface (API). To date, seven databases can exchange data using the API (GeneMatcher, PhenomeCentral, DECIPHER, MyGene2, matchbox, Australian Genomics Health Alliance Patient Archive, and Monarch Initiative; the latter included for model organism matching). This article guides usage of the MME for rare disease gene discovery. © 2017 by John Wiley & Sons, Inc.

Keywords: Australian Genomics Health Alliance Patient Archive; DECIPHER; GeneMatcher; MyGene2; PhenomeCentral; candidate genes; matchbox; matchmaker exchange; monarch initiative.

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Figures

Figure 1
Figure 1
Matchmaker Exchange Homepage.
Figure 2
Figure 2
Matchmaker exchange overview.
Figure 3
Figure 3
How to get started.
Figure 4
Figure 4
Database location and types of data stored by each database.
Figure 5
Figure 5
Parameters used for matching and score output.
Figure 6
Figure 6
Matchmaker exchange connections.
Figure 7
Figure 7
Types of users allowed in each Matchmaker exchange database.
Figure 8
Figure 8
How to create a general submission in GeneMatcher. Step 1 - Identify the organism being investigated. Step 2 - Classify the phenotype being investigated. Step 3 - Give pedigree information and add the features of the affected family members. Step 4 - Add gene name information, and variant information. Step 5 - Choose what data to match on. Step 3A - By clicking at “Add features” the user is taken to a page were features can be added.
Figure 8
Figure 8
How to create a general submission in GeneMatcher. Step 1 - Identify the organism being investigated. Step 2 - Classify the phenotype being investigated. Step 3 - Give pedigree information and add the features of the affected family members. Step 4 - Add gene name information, and variant information. Step 5 - Choose what data to match on. Step 3A - By clicking at “Add features” the user is taken to a page were features can be added.
Figure 9
Figure 9
How to send data from GeneMatcher to other Matchmaker exchange databases.
Figure 10
Figure 10
In GeneMatcher, matches are displayed at the Match Report tab.
Figure 11
Figure 11
Recording the outcome of a match follow up in GeneMatcher.
Figure 12
Figure 12
PhenomeCentral users can enable matching over the Matchmaker exchange by checking the corresponding consent box when creating or editing a patient record.
Figure 13
Figure 13
PhenomeCentral users can find and view matches in other Matchmaker exchange databases by viewing a patient record, scrolling to the “Matches in partner Matchmaker exchange databases” section, and clicking “Find matches” next to the desired database (or “Refresh matches” to send a new request). Matches can then be reviewed and expanded to see a phenotype and genotype comparison. If the match is promising, the Contact link can be clicked to send an email to the other researcher or view a webpage with more information.
Figure 14
Figure 14
Matchmaker exchange tab in a patient record in the DECIPHER database.
Figure 15
Figure 15
Matchmaker Exchange Dashboard in the MyGene2 database.
Figure 16
Figure 16
Collaborators of the Broad CMG use the seqr web platform for analysis. matchbox is embedded within it, and is our bridge to the Matchmaker Exchange. Our collaborators first annotate phenotypes and candidate genotypes [1], and then select genes and phenotypes to submit and search with [2]. Then seqr, with the help of matchbox, finds similar patients globally and summarizes the information [3].
Figure 17
Figure 17
How to send data from Australian Genomics Health Alliance Patient Archive to other Matchmaker exchange databases.
Figure 18
Figure 18
Display of Matchmaker exchange matches in the Australian Genomics Health Alliance Patient Archive.
See this image and copyright information in PMC

References

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