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Title: The Matchmaker Exchange: A Platform for Rare Disease Gene Discovery

Journal Article · · Human Mutation
DOI:https://doi.org/10.1002/humu.22858· OSTI ID:1377611
 [1];  [2];  [3];  [4];  [5];  [6];  [7];  [6];  [8];  [9];  [10];  [11];  [12];  [13];  [14];  [15];  [16];  [17];  [18];  [5] more »;  [19];  [20];  [20];  [21];  [10];  [22];  [23];  [24];  [25];  [26];  [18];  [27];  [28];  [29];  [22];  [30];  [31];  [32] « less
  1. Broad Inst. of Harvard and MIT, Cambridge, MA (United States); Brigham and Women's Hospital (Harvard Medical School), Boston, MA (United States). Dept. of Cardiology
  2. Partners Personalized Medicine, Boston, MA (United States). Lab. for Molecular Medicine
  3. Centro Nacional de Analisis Genomico, Barcelona (Spain)
  4. Univ. of Leicester (United Kingdom). Dept. of Genetics
  5. Harvard Univ., Boston, MA (United States). Harvard Medical School; Boston Children's Hospital, Boston, MA (United States). Division of Genetics and Genomics and the Manton Center for Orphan Disease Research
  6. Univ. of Toronto, ON (Canada). Dept. of Computer Science; The Hospital for Sick Children, Toronto (Canada). Genetics and Genome Biology Program; The Hospital for Sick Children, Toronto (Canada). Centre for Computational Medicine
  7. Radboud Univ. Medical Center, Nijmegen (The Netherlands). Dept. of Human Genetics; Maastricht Univ. (The Netherlands). Dept. of Clinical Genetics
  8. Gene Cloud, CA (United States)
  9. Google Inc., Mountain View, CA (United States)
  10. The Hospital for Sick Children, Toronto (Canada). Centre for Computational Medicine
  11. McGill Univ., Montreal, QC (Canada). Centre of Genomics and Policy
  12. Leiden Univ. Medical Center, Leiden (The Netherlands)
  13. Cambridge Univ. Hospitals NHS Foundation Trust, Cambridge (United Kingdom). Biomedical Campus, East Anglian Medical Genetics Service
  14. Baylor College of Medicine, Houston, TX (United States). Human Genome Sequencing Center
  15. Univ. of Toronto, ON (Canada). Dept. of Computer Science; The Hospital for Sick Children, Toronto (Canada). Centre for Computational Medicine
  16. Genesis Project Inc, Miami, FL (United States)
  17. Oregon Health & Science Univ., Portland, OR (United States). Dept. of Medical Informatics and Clinical Epidemiology
  18. Johns Hopkins Univ., Baltimore, MD (United States). McKusick-Nathans Inst. of Genetic Medicine
  19. Children's Hospital of Eastern Ontario Research Inst., Ottawa, ON (Canada)
  20. Wellcome Trust Sanger Inst., Hinxton (United Kingdom). Wellcome Trust Genome Campus
  21. Brigham and Women's Hospital, Boston, MA (United States). Division of Genetics, Dept. of Medicine
  22. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Genomics Division
  23. European Molecular Biology Lab. - European Bioinformatics Inst. (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridgeshire (United Kingdom)
  24. Univ. of California, Santa Cruz, CA (United States). Genomics Inst.
  25. Charite-Univ., Berlin (Germany); Max Planck Inst. for Molecular Genetics, Berlin (Germany); Freie Univ., Berlin (Germany). Dept. of Mathematics and Computer Science; Berlin Brandenburg Center for Regenerative Therapies, Berlin (Germany)
  26. FS Consulting LLC, Salem, MA (United States)
  27. Wellcome Trust Genome Campus, Hinxton, Cambridgeshire (United Kingdom)
  28. Oregon Health & Science Univ., Portland, OR (United States). Dept. of Medical Informatics and Clinical Epidemiology; Brigham and Women's Hospital, Boston, MA (United States). Division of Genetics, Dept. of Medicine
  29. Genetic Alliance, Washington, DC (United States)
  30. Univ. of Miami, Miami, FL (United States). Dr. John T. Macdonald Foundation Dept. of Human Genetics and John P. Hussman Inst. for Human Genomics
  31. Children's Hospital of Eastern Ontario, Ottawa, ON (Canada). Dept. of Genetics
  32. Broad Inst. of Harvard and MIT, Cambridge, MA (United States); Harvard Univ., Boston, MA (United States). Harvard Medical School; Partners Personalized Medicine, Boston, MA (United States). Lab. for Molecular Medicine; Brigham and Women's Hospital, Boston, MA (United States). Dept. of Pathology
+ Show Author Affiliations

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. In conclusion, 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.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH); Canadian Institutes of Health Research; Wellcome Trust; European Union (EU)
Grant/Contract Number:
AC02-05CH11231; U41HG006834; U54HG007990; HG007530; HG007690; HD077671; PPRN-1306-04899; 1U54HG006542; N01CO42400-80; WT098051; 305444; U54 HG003273; EP1-120608; EP2-120609
OSTI ID:
1377611
Journal Information:
Human Mutation, Vol. 36, Issue 10; ISSN 1059-7794
Publisher:
WileyCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 287 works
Citation information provided by
Web of Science

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The epilepsy phenotypic spectrum associated with a recurrent CUX2 variant: CUX2 and Epilepsy With Intellectual Disability journal April 2018
Exome sequencing of family trios from the National Birth Defects Prevention Study: Tapping into a rich resource of genetic and environmental data journal July 2019
Use of Model Organism and Disease Databases to Support Matchmaking for Human Disease Gene Discovery journal September 2015
BRCA Share: A Collection of Clinical BRCA Gene Variants: HUMAN MUTATION journal September 2016
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matchbox : An open-source tool for patient matching via the Matchmaker Exchange journal October 2018
Deleterious de novo variants of X‐linked ZC4H2 in females cause a variable phenotype with neurogenic arthrogryposis multiplex congenita journal August 2019
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Genetics in mainstream medicine: Finally within grasp to influence healthcare globally journal May 2018
The Role of Solidarity(-ies) in Rare Diseases Research book January 2017
Preparing Data at the Source to Foster Interoperability across Rare Disease Resources book January 2017
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New insights into the generation and role of de novo mutations in health and disease journal November 2016
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Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder journal September 2015
Paediatric genomics: diagnosing rare disease in children journal February 2018
Complexity in unclassified auto-inflammatory disease: a case report illustrating the potential for disease arising from the allelic burden of multiple variants text January 2019
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A systematic review and standardized clinical validity assessment of male infertility genes journal March 2019
Genomic variant sharing: a position statement. text January 2019
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Leveraging European infrastructures to access 1 million human genomes by 2022 text January 2019
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The role of the clinician in the multi-omics era: are you ready? journal January 2018
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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
matchmaking
rare disease
genomic API
gene discovery
Matchmaker Exchange
GA4GH
IRDiRC