TY - JOUR
T1 - Outcome of over 1500 matches through the Matchmaker Exchange for rare disease gene discovery
T2 - The 2-year experience of Care4Rare Canada
AU - Osmond, Matthew
AU - Hartley, Taila
AU - Dyment, David A.
AU - Kernohan, Kristin D.
AU - Care4Rare Canada Consortium
AU - Brudno, Michael
AU - Buske, Orion J.
AU - Innes, A. Micheil
AU - Boycott, Kym M.
AU - Boycott, Kym
AU - Bernier, Francois
AU - van Karnebeek, Clara
AU - Dyment, David
AU - Kernohan, Kristin
AU - Innes, Micheil
AU - Lamont, Ryan
AU - Parboosingh, Jillian
AU - Marshall, Deborah
AU - Marshall, Christian
AU - Mendoza, Roberto
AU - Dowling, James
AU - Hayeems, Robin
AU - Knoppers, Bartha
AU - Lehman, Anna
AU - Mostafavi, Sara
N1 - Funding Information: This work was performed under the Care4Rare Canada Consortium funded by Genome Canada and the Ontario Genomics Institute (OGI-147), the Canadian Institutes of Health Research, Ontario Research Fund, Genome Alberta, Genome British Columbia, Genome Quebec, and Children’s Hospital of Eastern Ontario Foundation. T.H. was supported by a Frederick Banting and Charles Best Canada Graduate Scholarship Doctoral Award from Canadian Institutes of Health Research. K.M.B. was supported by a Canadian Institutes of Health Research Foundation grant FDN-154279 and a Tier 1 Canada Research Chair in Rare Disease Precision Health. Funding Information: This work was performed under the Care4Rare Canada Consortium funded by Genome Canada and the Ontario Genomics Institute (OGI-147), the Canadian Institutes of Health Research, Ontario Research Fund, Genome Alberta, Genome British Columbia, Genome Quebec, and Children's Hospital of Eastern Ontario Foundation. T.H. was supported by a Frederick Banting and Charles Best Canada Graduate Scholarship Doctoral Award from Canadian Institutes of Health Research. K.M.B. was supported by a Canadian Institutes of Health Research Foundation grant FDN-154279 and a Tier 1 Canada Research Chair in Rare Disease Precision Health. Conceptualization: M.O. T.H. K.M.B.; Data Curation: M.O.; Formal Analysis: M.O.; Funding Acquisition: D.A.D. K.D.K. M.B. A.M.I. K.M.B.; Investigation: M.O. T.H.; Methodology: M.O. T.H.; Project Administration: T.H. K.M.B.; Resources: T.H. K.D.K. K.M.B.; Visualization: M.O.; Writing-original draft: M.O. T.H. K.M.B.; Writing-review and editing: M.O. T.H. D.A.D. K.D.K. O.J.B. A.M.I. K.M.B. Informed consent was obtained for all participants in this study. Individual-level data shared for the purposes of matchmaking was de-identified. Institutional review board approval was obtained from the Children's Hospital of Eastern Ontario for both Finding of Rare Disease Genes in Canada (FORGE) and Care4Rare Canada (Research Ethics Board # 11/04E). Institutional review board approval for Care4Rare-SOLVE was obtained by Clinical Trials Ontario (REB# 18/19CTO). Kym Boycott, Michael Brudno, Francois Bernier, Clara van Karnebeek, David Dyment, Kristin Kernohan, Micheil Innes, Ryan Lamont, Jillian Parboosingh, Deborah Marshall, Christian Marshall, Roberto Mendoza, James Dowling, Robin Hayeems, Bartha Knoppers, Anna Lehman, Sara Mostafavi. A full list of authors and their affiliations appears in the Supplemental Note. Publisher Copyright: © 2021 The Authors
PY - 2022/1/1
Y1 - 2022/1/1
N2 - Purpose: Matchmaking has emerged as a useful strategy for building evidence toward causality of novel disease genes in patients with undiagnosed rare diseases. The Matchmaker Exchange (MME) is a collaborative initiative that facilitates international data sharing for matchmaking purposes; however, data on user experience is limited. Methods: Patients enrolled as part of the Finding of Rare Disease Genes in Canada (FORGE) and Care4Rare Canada research programs had their exome sequencing data reanalyzed by a multidisciplinary research team over a 2-year period. Compelling variants in genes not previously associated with a human phenotype were submitted through the MME node PhenomeCentral, and outcomes were collected. Results: In this study, 194 novel candidate genes were submitted to the MME, resulting in 1514 matches, and 15% of the genes submitted resulted in collaborations. Most submissions resulted in at least 1 match, and most matches were with GeneMatcher (82%), where additional email exchange was required to evaluate the match because of the lack of phenotypic or inheritance information. Conclusion: Matchmaking through the MME is an effective way to investigate novel candidate genes; however, it is a labor-intensive process. Engagement from the community to contribute phenotypic, genotypic, and inheritance data will ensure that matchmaking continues to be a useful approach in the future.
AB - Purpose: Matchmaking has emerged as a useful strategy for building evidence toward causality of novel disease genes in patients with undiagnosed rare diseases. The Matchmaker Exchange (MME) is a collaborative initiative that facilitates international data sharing for matchmaking purposes; however, data on user experience is limited. Methods: Patients enrolled as part of the Finding of Rare Disease Genes in Canada (FORGE) and Care4Rare Canada research programs had their exome sequencing data reanalyzed by a multidisciplinary research team over a 2-year period. Compelling variants in genes not previously associated with a human phenotype were submitted through the MME node PhenomeCentral, and outcomes were collected. Results: In this study, 194 novel candidate genes were submitted to the MME, resulting in 1514 matches, and 15% of the genes submitted resulted in collaborations. Most submissions resulted in at least 1 match, and most matches were with GeneMatcher (82%), where additional email exchange was required to evaluate the match because of the lack of phenotypic or inheritance information. Conclusion: Matchmaking through the MME is an effective way to investigate novel candidate genes; however, it is a labor-intensive process. Engagement from the community to contribute phenotypic, genotypic, and inheritance data will ensure that matchmaking continues to be a useful approach in the future.
KW - Data sharing
KW - GeneMatcher
KW - Matchmaker exchange
KW - PhenomeCentral
KW - Rare diseases
UR - http://www.scopus.com/inward/record.url?scp=85122402501&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.gim.2021.08.014
DO - https://doi.org/10.1016/j.gim.2021.08.014
M3 - Article
C2 - 34906465
SN - 1098-3600
VL - 24
SP - 100
EP - 108
JO - Genetics in medicine
JF - Genetics in medicine
IS - 1
ER -