title: Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine.
abstract: Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine.
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA; Partners Personalized Medicine, Boston, MA 02139, USA. Electronic address: rcgreen@genetics.med.harvard.edu.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Green
authors.affiliation: Center for Health Research, Kaiser Permanente Northwest, Portland, OR 97227, USA.
authors.forename: Katrina A B
authors.initials: KAB
authors.lastname: Goddard
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA; Clinical Sequencing Exploratory Research Coordinating Center, University of Washington, Seattle, WA 98195, USA.
authors.forename: Gail P
authors.initials: GP
authors.lastname: Jarvik
authors.affiliation: Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA; Clinical Sequencing Exploratory Research Coordinating Center, University of Washington, Seattle, WA 98195, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Amendola
authors.affiliation: Department of Psychiatry, Columbia University Medical Center and New York State Psychiatric Institute, New York, NY 10032, USA.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Appelbaum
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Berg
authors.affiliation: Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Bernhardt
authors.affiliation: Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Leslie G
authors.initials: LG
authors.lastname: Biesecker
authors.affiliation: Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Sawona
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authors.lastname: Biswas
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Blout
authors.affiliation: HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA.
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authors.initials: KM
authors.lastname: Bowling
authors.affiliation: Department of Pediatrics, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Kyle B
authors.initials: KB
authors.lastname: Brothers
authors.affiliation: Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA; Clinical Sequencing Exploratory Research Coordinating Center, University of Washington, Seattle, WA 98195, USA; Department of Bioethics and Humanities, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Wylie
authors.initials: W
authors.lastname: Burke
authors.affiliation: National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Charlisse F
authors.initials: CF
authors.lastname: Caga-Anan
authors.affiliation: Michigan Center for Translational Pathology, Ann Arbor, MI 48109, USA; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA; Departments of Pathology and Urology, University of Michigan, Ann Arbor, MI 48109, USA; Howard Hughes Medical Institute, Ann Arbor, MI 48109, USA.
authors.forename: Arul M
authors.initials: AM
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authors.affiliation: Department of Pediatrics, Columbia University, New York, NY 10029, USA; Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.
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authors.initials: WK
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authors.affiliation: Center for Biomedical Ethics and Society, Vanderbilt University, Nashville, TN 37203, USA.
authors.forename: Ellen W
authors.initials: EW
authors.lastname: Clayton
authors.affiliation: HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA.
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authors.initials: GM
authors.lastname: Cooper
authors.affiliation: HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA.
authors.forename: Kelly
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authors.lastname: East
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Evans
authors.affiliation: Department of Bioethics and Humanities, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
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authors.initials: SM
authors.lastname: Fullerton
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology and Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Levi A
authors.initials: LA
authors.lastname: Garraway
authors.affiliation: Children's Mercy Bioethics Center, Children's Mercy Hospital, Kansas City, MO 64108, USA; Departments of Pediatrics and Philosophy, University of Missouri - Kansas City, Kansas City, MO 64110, USA.
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Garrett
authors.affiliation: Harvard Medical School, Boston, MA 02115, USA; Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Stacy W
authors.initials: SW
authors.lastname: Gray
authors.affiliation: Department of Social Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
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authors.initials: GE
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authors.affiliation: Division of Genomic Medicine, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
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authors.lastname: Hindorff
authors.affiliation: Harvard Medical School, Boston, MA 02115, USA; Division of Genetics and Genomics and the Manton Center for Orphan Diseases Research, Boston Children's Hospital, Boston, MA 02115, USA.
authors.forename: Ingrid A
authors.initials: IA
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authors.affiliation: Berman Institute of Bioethics, Johns Hopkins, Baltimore, MD 21205, USA.
authors.forename: Michelle Huckaby
authors.initials: MH
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authors.affiliation: Division of Genomic Medicine, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Carolyn M
authors.initials: CM
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authors.affiliation: Harvard Medical School, Boston, MA 02115, USA; Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Pasi A
authors.initials: PA
authors.lastname: Janne
authors.affiliation: Department of Medical Ethics & Health Policy, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Joffe
authors.affiliation: Division of Genomics and Society, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
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authors.lastname: Kaufman
authors.affiliation: Centre of Genomics and Policy, Faculty of Medicine, Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada.
authors.forename: Bartha M
authors.initials: BM
authors.lastname: Knoppers
authors.affiliation: Institute for Health and Aging, University of California, San Francisco, San Francisco, CA 94118, USA.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Koenig
authors.affiliation: Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Ian D
authors.initials: ID
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authors.affiliation: Division of Genomic Medicine, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Teri A
authors.initials: TA
authors.lastname: Manolio
authors.affiliation: Center for Medical Ethics and Health Policy, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Laurence
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authors.lastname: McCullough
authors.affiliation: Division of Genomics and Society, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
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authors.affiliation: Center for Medical Ethics and Health Policy, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: McGuire
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Donna
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authors.lastname: Muzny
authors.affiliation: HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA.
authors.forename: Richard M
authors.initials: RM
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authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Clinical Sequencing Exploratory Research Coordinating Center, University of Washington, Seattle, WA 98195, USA.
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authors.initials: DA
authors.lastname: Nickerson
authors.affiliation: Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA; Clinical Sequencing Exploratory Research Coordinating Center, University of Washington, Seattle, WA 98195, USA.
authors.forename: Jeffrey
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authors.affiliation: Baylor College of Medicine and Texas Children's Cancer Center, Houston, TX 77030, USA.
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authors.affiliation: Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
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authors.affiliation: Baylor College of Medicine and Texas Children's Cancer Center, Houston, TX 77030, USA.
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authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA; Partners Personalized Medicine, Boston, MA 02139, USA; Laboratory for Molecular Medicine, Partners HealthCare, Cambridge, MA 02139, USA.
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authors.affiliation: Michigan Center for Translational Pathology, Ann Arbor, MI 48109, USA.
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authors.affiliation: Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA; Clinical Sequencing Exploratory Research Coordinating Center, University of Washington, Seattle, WA 98195, USA.
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authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.
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authors.affiliation: Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA; University of Washington, Seattle, WA 98105, USA.
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authors.affiliation: Department of Pharmacy, University of Washington, Seattle, WA 98195, USA.
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authors.lastname: Veenstra
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology and Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Nikhil
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authors.initials: BS
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authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
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mesh_terms: D000328:Adult; D035843:Biomedical Research; D002318:Cardiovascular Diseases / Q000235:genetics; D002648:Child; D002986:Clinical Trials as Topic; D055317:Evidence-Based Practice; D059472:Exome / Q000235:genetics*; D015894:Genome, Human; D023281:Genomics / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D054560:National Human Genome Research Institute (U.S.); D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044382:Population Groups; D012984:Software; D014481:United States