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Title: 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. 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.

Authors:
 [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
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); National Institutes of Health (NIH); Canadian Institutes of Health Research; Wellcome Trust; European Union (EU)
OSTI Identifier:
1377611
DOE Contract Number:  
AC02-05CH11231; U41HG006834; U54HG007990; HG007530; HG007690; HD077671; PPRN-1306-04899; 1U54HG006542; N01CO42400-80; WT098051; 305444; U54 HG003273; EP1-120608; EP2-120609
Resource Type:
Journal Article
Journal Name:
Human Mutation
Additional Journal Information:
Journal Volume: 36; Journal Issue: 10; Journal ID: ISSN 1059-7794
Publisher:
Wiley
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; matchmaking; rare disease; genomic API; gene discovery; Matchmaker Exchange; GA4GH, IRDiRC

Citation Formats

Philippakis, Anthony A., Azzariti, Danielle R., Beltran, Sergi, Brookes, Anthony J., Brownstein, Catherine A., Brudno, Michael, Brunner, Han G., Buske, Orion J., Carey, Knox, Doll, Cassie, Dumitriu, Sergiu, Dyke, Stephanie O. M., den Dunnen, Johan T., Firth, Helen V., Gibbs, Richard A., Girdea, Marta, Gonzalez, Michael, Haendel, Melissa A., Hamosh, Ada, Holm, Ingrid A., Huang, Lijia, Hurles, Matthew E., Hutton, Ben, Krier, Joel B., Misyura, Andriy, Mungall, Christopher J., Paschall, Justin, Paten, Benedict, Robinson, Peter N., Schiettecatte, François, Sobreira, Nara L., Swaminathan, Ganesh J., Taschner, Peter E., Terry, Sharon F., Washington, Nicole L., Züchner, Stephan, Boycott, Kym M., and Rehm, Heidi L. The Matchmaker Exchange: A Platform for Rare Disease Gene Discovery. United States: N. p., 2015. Web. doi:10.1002/humu.22858.
Philippakis, Anthony A., Azzariti, Danielle R., Beltran, Sergi, Brookes, Anthony J., Brownstein, Catherine A., Brudno, Michael, Brunner, Han G., Buske, Orion J., Carey, Knox, Doll, Cassie, Dumitriu, Sergiu, Dyke, Stephanie O. M., den Dunnen, Johan T., Firth, Helen V., Gibbs, Richard A., Girdea, Marta, Gonzalez, Michael, Haendel, Melissa A., Hamosh, Ada, Holm, Ingrid A., Huang, Lijia, Hurles, Matthew E., Hutton, Ben, Krier, Joel B., Misyura, Andriy, Mungall, Christopher J., Paschall, Justin, Paten, Benedict, Robinson, Peter N., Schiettecatte, François, Sobreira, Nara L., Swaminathan, Ganesh J., Taschner, Peter E., Terry, Sharon F., Washington, Nicole L., Züchner, Stephan, Boycott, Kym M., & Rehm, Heidi L. The Matchmaker Exchange: A Platform for Rare Disease Gene Discovery. United States. doi:10.1002/humu.22858.
Philippakis, Anthony A., Azzariti, Danielle R., Beltran, Sergi, Brookes, Anthony J., Brownstein, Catherine A., Brudno, Michael, Brunner, Han G., Buske, Orion J., Carey, Knox, Doll, Cassie, Dumitriu, Sergiu, Dyke, Stephanie O. M., den Dunnen, Johan T., Firth, Helen V., Gibbs, Richard A., Girdea, Marta, Gonzalez, Michael, Haendel, Melissa A., Hamosh, Ada, Holm, Ingrid A., Huang, Lijia, Hurles, Matthew E., Hutton, Ben, Krier, Joel B., Misyura, Andriy, Mungall, Christopher J., Paschall, Justin, Paten, Benedict, Robinson, Peter N., Schiettecatte, François, Sobreira, Nara L., Swaminathan, Ganesh J., Taschner, Peter E., Terry, Sharon F., Washington, Nicole L., Züchner, Stephan, Boycott, Kym M., and Rehm, Heidi L. Thu . "The Matchmaker Exchange: A Platform for Rare Disease Gene Discovery". United States. doi:10.1002/humu.22858. https://www.osti.gov/servlets/purl/1377611.
@article{osti_1377611,
title = {The Matchmaker Exchange: A Platform for Rare Disease Gene Discovery},
author = {Philippakis, Anthony A. and Azzariti, Danielle R. and Beltran, Sergi and Brookes, Anthony J. and Brownstein, Catherine A. and Brudno, Michael and Brunner, Han G. and Buske, Orion J. and Carey, Knox and Doll, Cassie and Dumitriu, Sergiu and Dyke, Stephanie O. M. and den Dunnen, Johan T. and Firth, Helen V. and Gibbs, Richard A. and Girdea, Marta and Gonzalez, Michael and Haendel, Melissa A. and Hamosh, Ada and Holm, Ingrid A. and Huang, Lijia and Hurles, Matthew E. and Hutton, Ben and Krier, Joel B. and Misyura, Andriy and Mungall, Christopher J. and Paschall, Justin and Paten, Benedict and Robinson, Peter N. and Schiettecatte, François and Sobreira, Nara L. and Swaminathan, Ganesh J. and Taschner, Peter E. and Terry, Sharon F. and Washington, Nicole L. and Züchner, Stephan and Boycott, Kym M. and Rehm, Heidi L.},
abstractNote = {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.},
doi = {10.1002/humu.22858},
journal = {Human Mutation},
issn = {1059-7794},
number = 10,
volume = 36,
place = {United States},
year = {2015},
month = {9}
}

Works referenced in this record:

GEnomes Management Application (GEM.app): A New Software Tool for Large-Scale Collaborative Genome Analysis
journal, April 2013

  • Gonzalez, Michael A.; Lebrigio, Rafael F. Acosta; Van Booven, Derek
  • Human Mutation, Vol. 34, Issue 6
  • DOI: 10.1002/humu.22305

GeneMatcher: A Matching Tool for Connecting Investigators with an Interest in the Same Gene
journal, August 2015

  • Sobreira, Nara; Schiettecatte, François; Valle, David
  • Human Mutation, Vol. 36, Issue 10
  • DOI: 10.1002/humu.22844

The Genomic Birthday Paradox: How Much Is Enough?: HUMAN MUTATION
journal, August 2015

  • Krawitz, Peter; Buske, Orion; Zhu, Na
  • Human Mutation, Vol. 36, Issue 10
  • DOI: 10.1002/humu.22848

DECIPHER: web-based, community resource for clinical interpretation of rare variants in developmental disorders
journal, September 2012

  • Swaminathan, G. J.; Bragin, E.; Chatzimichali, E. A.
  • Human Molecular Genetics, Vol. 21, Issue R1
  • DOI: 10.1093/hmg/dds362

Linking Human Diseases to Animal Models Using Ontology-Based Phenotype Annotation
journal, November 2009


Mitigating False-Positive Associations in Rare Disease Gene Discovery
journal, September 2015

  • Akle, Sebastian; Chun, Sung; Jordan, Daniel M.
  • Human Mutation, Vol. 36, Issue 10
  • DOI: 10.1002/humu.22847

Facilitating Collaboration in Rare Genetic Disorders Through Effective Matchmaking in DECIPHER
journal, August 2015

  • Chatzimichali, Eleni A.; Brent, Simon; Hutton, Benjamin
  • Human Mutation, Vol. 36, Issue 10
  • DOI: 10.1002/humu.22842

Cafe Variome: General-Purpose Software for Making Genotype-Phenotype Data Discoverable in Restricted or Open Access Contexts
journal, August 2015

  • Lancaster, Owen; Beck, Tim; Atlan, David
  • Human Mutation, Vol. 36, Issue 10
  • DOI: 10.1002/humu.22841

Data Sharing in the Undiagnosed Diseases Network
journal, August 2015

  • Brownstein, Catherine A.; Holm, Ingrid A.; Ramoni, Rachel
  • Human Mutation, Vol. 36, Issue 10
  • DOI: 10.1002/humu.22840

International Cancer Genome Consortium Data Portal--a one-stop shop for cancer genomics data
journal, January 2011


Use of Model Organism and Disease Databases to Support Matchmaking for Human Disease Gene Discovery
journal, September 2015

  • Mungall, Christopher J.; Washington, Nicole L.; Nguyen-Xuan, Jeremy
  • Human Mutation, Vol. 36, Issue 10
  • DOI: 10.1002/humu.22857

Improved exome prioritization of disease genes through cross-species phenotype comparison
journal, October 2013


GenomeConnect: Matchmaking Between Patients, Clinical Laboratories, and Researchers to Improve Genomic Knowledge
journal, August 2015

  • Kirkpatrick, Brianne E.; Riggs, Erin Rooney; Azzariti, Danielle R.
  • Human Mutation, Vol. 36, Issue 10
  • DOI: 10.1002/humu.22838

The Cancer Genome Atlas Pan-Cancer analysis project
journal, September 2013

  • Weinstein, John N.; Collisson, Eric A.; Mills, Gordon B.
  • Nature Genetics, Vol. 45, Issue 10
  • DOI: 10.1038/ng.2764

Innovative Genomic Collaboration Using the GENESIS (GEM.app) Platform
journal, August 2015

  • Gonzalez, Michael; Falk, Marni J.; Gai, Xiaowu
  • Human Mutation, Vol. 36, Issue 10
  • DOI: 10.1002/humu.22836

Genetic Mapping in Human Disease
journal, November 2008


PheWAS: demonstrating the feasibility of a phenome-wide scan to discover gene-disease associations
journal, March 2010


Participant-Driven Matchmaking in the Genomic Era
journal, August 2015

  • Lambertson, Katherine F.; Damiani, Stephen A.; Might, Matthew
  • Human Mutation, Vol. 36, Issue 10
  • DOI: 10.1002/humu.22852

PhenomeCentral: A Portal for Phenotypic and Genotypic Matchmaking of Patients with Rare Genetic Diseases
journal, August 2015

  • Buske, Orion J.; Girdea, Marta; Dumitriu, Sergiu
  • Human Mutation, Vol. 36, Issue 10
  • DOI: 10.1002/humu.22851

Effective diagnosis of genetic disease by computational phenotype analysis of the disease-associated genome
journal, September 2014

  • Zemojtel, Tomasz; Köhler, Sebastian; Mackenroth, Luisa
  • Science Translational Medicine, Vol. 6, Issue 252
  • DOI: 10.1126/scitranslmed.3009262

The Matchmaker Exchange API: Automating Patient Matching Through the Exchange of Structured Phenotypic and Genotypic Profiles
journal, September 2015

  • Buske, Orion J.; Schiettecatte, François; Hutton, Benjamin
  • Human Mutation, Vol. 36, Issue 10
  • DOI: 10.1002/humu.22850

Whole Genome Sequencing and a New Bioinformatics Platform Allow for Rapid Gene Identification in D. melanogaster EMS Screens
journal, December 2012


    Works referencing / citing this record:

    Genomic variant sharing: a position statement
    journal, January 2019


    MIPEP recessive variants cause a syndrome of left ventricular non-compaction, hypotonia, and infantile death
    journal, November 2016

    • Eldomery, Mohammad K.; Akdemir, Zeynep C.; Vögtle, F. -Nora
    • Genome Medicine, Vol. 8, Issue 1
    • DOI: 10.1186/s13073-016-0360-6

    Genetic diagnosis in first or second trimester pregnancy loss using exome sequencing: a systematic review of human essential genes
    journal, July 2019

    • Robbins, Sarah M.; Thimm, Matthew A.; Valle, David
    • Journal of Assisted Reproduction and Genetics, Vol. 36, Issue 8
    • DOI: 10.1007/s10815-019-01499-6

    GenIO: a phenotype-genotype analysis web server for clinical genomics of rare diseases
    journal, January 2018

    • Koile, Daniel; Cordoba, Marta; de Sousa Serro, Maximiliano
    • BMC Bioinformatics, Vol. 19, Issue 1
    • DOI: 10.1186/s12859-018-2027-3

    Registered access: authorizing data access
    journal, August 2018

    • Dyke, Stephanie O. M.; Linden, Mikael; Lappalainen, Ilkka
    • European Journal of Human Genetics, Vol. 26, Issue 12
    • DOI: 10.1038/s41431-018-0219-y

    RD-Connect, NeurOmics and EURenOmics: collaborative European initiative for rare diseases
    journal, February 2018

    • Lochmüller, Hanns; Badowska, Dorota M.; Thompson, Rachel
    • European Journal of Human Genetics, Vol. 26, Issue 6
    • DOI: 10.1038/s41431-018-0115-5

    Text-based phenotypic profiles incorporating biochemical phenotypes of inborn errors of metabolism improve phenomics-based diagnosis
    journal, January 2018

    • Lee, Jessica J. Y.; Gottlieb, Michael M.; Lever, Jake
    • Journal of Inherited Metabolic Disease, Vol. 41, Issue 3
    • DOI: 10.1007/s10545-017-0125-4