Harmonizing Clinical Sequencing and Interpretation for the eMERGE III Network

the eMERGE Consortium

doi:10.1016/j.ajhg.2019.07.018

Harmonizing Clinical Sequencing and Interpretation for the eMERGE III Network

the eMERGE Consortium

Research output: Contribution to journal › Article › peer-review

83 Scopus citations

Abstract

The advancement of precision medicine requires new methods to coordinate and deliver genetic data from heterogeneous sources to physicians and patients. The eMERGE III Network enrolled >25,000 participants from biobank and prospective cohorts of predominantly healthy individuals for clinical genetic testing to determine clinically actionable findings. The network developed protocols linking together the 11 participant collection sites and 2 clinical genetic testing laboratories. DNA capture panels targeting 109 genes were used for testing of DNA and sample collection, data generation, interpretation, reporting, delivery, and storage were each harmonized. A compliant and secure network enabled ongoing review and reconciliation of clinical interpretations, while maintaining communication and data sharing between clinicians and investigators. A total of 202 individuals had positive diagnostic findings relevant to the indication for testing and 1,294 had additional/secondary findings of medical significance deemed to be returnable, establishing data return rates for other testing endeavors. This study accomplished integration of structured genomic results into multiple electronic health record (EHR) systems, setting the stage for clinical decision support to enable genomic medicine. Further, the established processes enable different sequencing sites to harmonize technical and interpretive aspects of sequencing tests, a critical achievement toward global standardization of genomic testing. The eMERGE protocols and tools are available for widespread dissemination.

Original language	English (US)
Pages (from-to)	588-605
Number of pages	18
Journal	American journal of human genetics
Volume	105
Issue number	3
DOIs	https://doi.org/10.1016/j.ajhg.2019.07.018
State	Published - Sep 5 2019

Funding

Samuel Aronson is employed at Partners HealthCare, which receives royalties on sales of GeneInsight Software. Samuel Aronson’s team receives funding from Sunquest and has received funding from Novartis for development of SMART on FHIR apps. Andrew Carroll is employed at Google Inc. and is a former employee of DNAnexus. Paul Crane served as a consultant to Eisai on efforts unrelated to this manuscript. David Crosslin serves on a consulting board for UnitedHealth Group with precision medicine efforts, which is unrelated to this manuscript. Christine Eng is a full-time employee/faculty member of Baylor College of Medicine. Through a professional services agreement, she serves as Chief Medical Officer and Chief Quality Officer of Baylor Genetics. Richard A. Gibbs declares that Baylor College of Medicine receives payments from Baylor Genetics Laboratories, which provides services for genetic testing; Baylor College of Medicine is part owner of Codified Genomics. Robert C. Green receives personal compensation from AIA, Applied Therapeutics, Helix, Prudential, Verily, and Veritas for speaking or consulting and is co-founder of Genome Medical, Inc. Eimear E. Kenny has received speaker honorariums from Illumina and Regeneron Pharmaceuticals. Niall J. Lennon is an advisor to Genturi Inc. Elizabeth McNally serves or has served as a consultant to Invitae, Tenaya, Exonics, Pfizer, AstraZeneca, Cytokinetics, and 4D Molecular Therapeutics and founded Ikaika Therapeutics. Thomas E. Mullen is employed at and a shareholder at Quest Diagnostics. Heidi Rehm is employed at Massachusetts General Hospital, which receives royalties on sales of GeneInsight Software. Avni Santani receives royalties from Agilent Technologies and a founder of Opus Genomics. Jordan W. Smoller is an unpaid member of the Bipolar/Depression Research Community Advisory Panel of 23andMe. Eric Venner is a cofounder of Codified Genomics. Theresa Walunas completed (in 2018) legal consulting for by Pfizer Inc., Wyeth LLC, Genetics Institute, LLC, Merck KGaA, and EMD Serono, Inc. Georgia L. Wiesner is a member of the External Advisory Panel for the ClinGen Clinical Genome Resource Project. Hana Zouk is employed at Massachusetts General Hospital which receives royalties on sales of GeneInsight Software. The eMERGE Phase III Network was initiated and funded by the National Human Genome Research Institute (NHGRI) through the following grants: U01HG8657 (Kaiser Permanente Washington Health Research Institute/University of Washington), U01HG8685 (Brigham and Women's Hospital), U01HG8672 (Vanderbilt University Medical Center), U01HG8666 (Cincinnati Children's Hospital Medical Center), U01HG6379 (Mayo Clinic), U01HG8679 (Geisinger Clinic), U01HG8680 (Columbia University Health Sciences), U01HG8684 (Children's Hospital of Philadelphia), U01HG8673 (Northwestern University), MD007593 (Meharry Medical College), U01HG8701 (Vanderbilt University Medical Center serving as the Coordinating Center), U01HG8676 (Partners Healthcare/Broad Institute), and U01HG8664 (Baylor College of Medicine).

Keywords

clinical sequencing
eMERGE
electronic health record
harmonization
next generation sequencing

ASJC Scopus subject areas

Genetics
Genetics(clinical)

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10.1016/j.ajhg.2019.07.018

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title = "Harmonizing Clinical Sequencing and Interpretation for the eMERGE III Network",

abstract = "The advancement of precision medicine requires new methods to coordinate and deliver genetic data from heterogeneous sources to physicians and patients. The eMERGE III Network enrolled >25,000 participants from biobank and prospective cohorts of predominantly healthy individuals for clinical genetic testing to determine clinically actionable findings. The network developed protocols linking together the 11 participant collection sites and 2 clinical genetic testing laboratories. DNA capture panels targeting 109 genes were used for testing of DNA and sample collection, data generation, interpretation, reporting, delivery, and storage were each harmonized. A compliant and secure network enabled ongoing review and reconciliation of clinical interpretations, while maintaining communication and data sharing between clinicians and investigators. A total of 202 individuals had positive diagnostic findings relevant to the indication for testing and 1,294 had additional/secondary findings of medical significance deemed to be returnable, establishing data return rates for other testing endeavors. This study accomplished integration of structured genomic results into multiple electronic health record (EHR) systems, setting the stage for clinical decision support to enable genomic medicine. Further, the established processes enable different sequencing sites to harmonize technical and interpretive aspects of sequencing tests, a critical achievement toward global standardization of genomic testing. The eMERGE protocols and tools are available for widespread dissemination.",

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author = "{the eMERGE Consortium} and Hana Zouk and Eric Venner and Lennon, {Niall J.} and Muzny, {Donna M.} and Debra Abrams and Samuel Adunyah and Ladia Albertson-Junkans and Ames, {Darren C.} and Paul Appelbaum and Samuel Aronson and Sharon Aufox and Babb, {Lawrence J.} and Adithya Balasubramanian and Hana Bangash and Melissa Basford and Lisa Bastarache and Samantha Baxter and Meckenzie Behr and Barbara Benoit and Elizabeth Bhoj and Bielinski, {Suzette J.} and Bland, {Harris T.} and Carrie Blout and Kenneth Borthwick and Bottinger, {Erwin P.} and Mark Bowser and Harrison Brand and Murray Brilliant and Wendy Brodeur and Pedro Caraballo and David Carrell and Andrew Carroll and Berta Almoguera and Lisa Castillo and Victor Castro and Gauthami Chandanavelli and Theodore Chiang and Chisholm, {Rex L.} and Christensen, {Kurt D.} and Wendy Chung and Chute, {Christopher G.} and Gordon, {Adam S.} and Hayes, {M. Geoffrey} and Christin Hoell and Elizabeth McNally and Puckelwartz, {Megan J.} and Laura Rasmussen-Torvik and Smith, {Maureen E.} and Justin Starren and Theresa Walunas",

note = "Publisher Copyright: {\textcopyright} 2019 American Society of Human Genetics",

year = "2019",

month = sep,

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doi = "10.1016/j.ajhg.2019.07.018",

language = "English (US)",

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AU - Lennon, Niall J.

AU - Muzny, Donna M.

AU - Abrams, Debra

AU - Adunyah, Samuel

AU - Albertson-Junkans, Ladia

AU - Ames, Darren C.

AU - Appelbaum, Paul

AU - Aronson, Samuel

AU - Aufox, Sharon

AU - Babb, Lawrence J.

AU - Balasubramanian, Adithya

AU - Bangash, Hana

AU - Basford, Melissa

AU - Bastarache, Lisa

AU - Baxter, Samantha

AU - Behr, Meckenzie

AU - Benoit, Barbara

AU - Bhoj, Elizabeth

AU - Bielinski, Suzette J.

AU - Bland, Harris T.

AU - Blout, Carrie

AU - Borthwick, Kenneth

AU - Bottinger, Erwin P.

AU - Bowser, Mark

AU - Brand, Harrison

AU - Brilliant, Murray

AU - Brodeur, Wendy

AU - Caraballo, Pedro

AU - Carrell, David

AU - Carroll, Andrew

AU - Almoguera, Berta

AU - Castillo, Lisa

AU - Castro, Victor

AU - Chandanavelli, Gauthami

AU - Chiang, Theodore

AU - Chisholm, Rex L.

AU - Christensen, Kurt D.

AU - Chung, Wendy

AU - Chute, Christopher G.

AU - Gordon, Adam S.

AU - Hayes, M. Geoffrey

AU - Hoell, Christin

AU - McNally, Elizabeth

AU - Puckelwartz, Megan J.

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AU - Starren, Justin

AU - Walunas, Theresa

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N2 - The advancement of precision medicine requires new methods to coordinate and deliver genetic data from heterogeneous sources to physicians and patients. The eMERGE III Network enrolled >25,000 participants from biobank and prospective cohorts of predominantly healthy individuals for clinical genetic testing to determine clinically actionable findings. The network developed protocols linking together the 11 participant collection sites and 2 clinical genetic testing laboratories. DNA capture panels targeting 109 genes were used for testing of DNA and sample collection, data generation, interpretation, reporting, delivery, and storage were each harmonized. A compliant and secure network enabled ongoing review and reconciliation of clinical interpretations, while maintaining communication and data sharing between clinicians and investigators. A total of 202 individuals had positive diagnostic findings relevant to the indication for testing and 1,294 had additional/secondary findings of medical significance deemed to be returnable, establishing data return rates for other testing endeavors. This study accomplished integration of structured genomic results into multiple electronic health record (EHR) systems, setting the stage for clinical decision support to enable genomic medicine. Further, the established processes enable different sequencing sites to harmonize technical and interpretive aspects of sequencing tests, a critical achievement toward global standardization of genomic testing. The eMERGE protocols and tools are available for widespread dissemination.

AB - The advancement of precision medicine requires new methods to coordinate and deliver genetic data from heterogeneous sources to physicians and patients. The eMERGE III Network enrolled >25,000 participants from biobank and prospective cohorts of predominantly healthy individuals for clinical genetic testing to determine clinically actionable findings. The network developed protocols linking together the 11 participant collection sites and 2 clinical genetic testing laboratories. DNA capture panels targeting 109 genes were used for testing of DNA and sample collection, data generation, interpretation, reporting, delivery, and storage were each harmonized. A compliant and secure network enabled ongoing review and reconciliation of clinical interpretations, while maintaining communication and data sharing between clinicians and investigators. A total of 202 individuals had positive diagnostic findings relevant to the indication for testing and 1,294 had additional/secondary findings of medical significance deemed to be returnable, establishing data return rates for other testing endeavors. This study accomplished integration of structured genomic results into multiple electronic health record (EHR) systems, setting the stage for clinical decision support to enable genomic medicine. Further, the established processes enable different sequencing sites to harmonize technical and interpretive aspects of sequencing tests, a critical achievement toward global standardization of genomic testing. The eMERGE protocols and tools are available for widespread dissemination.

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KW - eMERGE

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KW - harmonization

KW - next generation sequencing

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Harmonizing Clinical Sequencing and Interpretation for the eMERGE III Network

Abstract

Funding

Keywords

ASJC Scopus subject areas

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