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Clinical Sequencing Exploratory Research (CSER)

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Program poster


FAQ for Clinical Sequencing Evidence-Generating Research (CSER2) RFAs 

Program Rationale

Reports of genomic sequencing being applied to the medical care of individual patients are becoming more frequent, but much more needs to be done before the use of sequence data becomes routine. The potential range of clinical applications and the specific diseases or individual susceptibilities most likely to be usefully addressed by a genomic sequencing approach have yet to be determined. Furthermore, incorporation of comprehensive genomic sequence data into clinical care will require changes to institutional policies, standard procedures (including simplified analysis and interpretive tools), and the ability to integrate sequence information into the clinical workflow. The ethical, legal, and psychosocial implications of returning genomic variation data, with all of the caveats regarding statistical uncertainties, incomplete knowledge, and unanticipated findings, remain incompletely understood.

In 2010, NHGRI initiated a Clinical Sequencing Exploratory Research (CSER) program intended to support both the methods development needed to integrate sequencing into the clinic and the ethical, legal, and psychosocial research required to responsibly apply personal genomic sequence data to medical care. A U01 cooperative agreement mechanism was used to promote the development of a robust forum for scientific discussion as well as debate of issues, both practical and conceptual. In 2013, the program was extended for another funding cycle to bring in more diverse expertise and a larger number of clinical populations to support the goals of the consortium. The new awards (UM1s) are also cooperative agreements that encourage collaboration and discourse between disciplines under the banner of a common scientific goal. A CSER Coordinating Center at the University of Washington was also funded in 2013 to facilitate collaborative efforts among the CSER investigators and disseminate findings and approaches from the CSER program to the biomedical research community.

In addition to incorporating the UM1s, the CSER consortium was expanded in 2013 to include nine additional projects that formerly comprised the ELSI Return of Results Consortium. These studies (R01s and R21s), which incorporate both empirical and normative research methods, explore a broad range of ethical, legal and social implications relating to the return of research results in both research and clinical settings. The consolidation of these two consortia under the broader umbrella of CSER will make it possible for consideration of the ethical, legal, and psychosocial aspects of returning genomic results to better inform the implementation of genomic medicine.

In all, the CSER consortium supports nine multi-disciplinary projects, nine ELSI-specific projects, and a Coordinating Center that brings together clinicians, genomic researchers, bioinformaticians, ethicists and other investigators to research the challenges of utilizing genomic sequence data in the clinic in the routine practice of medicine. The challenges are many and not disease-specific. Important aims of the research include: generation of genomic sequence data on patients in a variety of clinical contexts; investigation of methods to interpret, translate and guide adoption of genomic data in a fashion and timescale that fits the normal clinical workflow; and study of the ethical, legal, and psychosocial implications of generating and returning genomic results, including returning incidental findings. The consortium of grantees will cooperate to evaluate best practices in this rapidly advancing field and communicate these to the community.

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Grantees of the Program

Phase I Clinical Sequencing Exploratory Research Groups
Institution Lead PI(s) Study Title Clinical Focus
Baylor College of Medicine Sharon Plon and D. Will Parsons Incorporation of Genomic Sequencing into Pediatric Cancer Care*
Childhood cancer patients with high-risk solid tumors and brain tumors
Brigham and Women's Hospital Robert C. Green
Integration of Whole Genome Sequencing into Clinical Medicine Primary care patients, cardiomyopathy patients
Children's Hospital of Philadelphia Ian Krantz and Nancy Spinner Applying Genomic Sequencing in Pediatrics Pediatric patients with one of four conditions - intellectual disability, sudden cardiac arrest/death, hearing loss, and mitochondrial disorders
Dana-Farber Cancer Institute Levi Garraway and Pasi Janne The Use of Whole-Exome Sequencing to Guide the Care of Cancer Patients Lung and colorectal cancer patients
University of North Carolina, Chapel Hill James Evans,
Jonathan Berg and
Gail Henderson

NC GENES [] Patients from one of five clinical domains - cancer, cardiology, dysmorphology, neurodevelopmental and ophthalmology
University of Washington, Seattle Gail Jarvik Clinical sequencing in cancer: Clinical, ethical, and technological studies* Patients who have clinical indications for colorectal cancer/polyposis (CRCP) genetic testing
Phase II Clinical Sequencing Exploratory Research Groups
Institution Lead PI(s) Study Title Clinical Focus
Hudson-Alpha Institute for Biotechnology Greg Cooper and Richard Myers
Genomic Diagnosis in Children with Developmental Delay Children with intellectual disability and/or developmental delay
Kaiser Foundation Research Institute Katrina Goddard and Benjamin Wilfond Clinical Implementation of Carrier Testing Using Next Generation Sequencing (NGS)

Women and their partners seeking pre-conception carrier testing
University of Michigan, Ann Arbor Arul Chinnaiyan Exploring Precision Cancer Medicine for Sarcoma and Rare Cancers* Patients with advanced sarcoma or other rare cancers
University of Washington, Seattle Gail Jarvik CSER Centralized Support Coordinating Center The coordinating center is responsible for facilitating the scientific work of the CSER consortium and its working group by providing logistical and scientific expertise. It will also be a key partner in disseminating findings and approaches from the CSER program to the biomedical research community.
Ethical, Legal, and Social Implications-specific Projects

Formerly comprising the Return of Results Consortium

Institution PI Study Title Grant Type
Cleveland Clinic Richard Sharp Presenting diagnostic results from large-scale clinical mutation testing R01
Columbia University Paul S. Appelbaum Challenges of informed consent in return of data from genomic research R21
Columbia University Wendy K. Chung Impact of return of incidental genetic test results to research participants in the genomic era R01
Children's Hospital Boston Ingrid A. Holm Returning research results in children: Parental Preferences and Expert Oversight R01
Children's Mercy Bioethics Center Jeremy R. Garrett The presumptive case against returning individual results in biobanking research R21
Johns Hopkins University Michelle Huckaby Lewis Return of research results from samples obtained for newborn screening R21
University of California, San Francisco Gloria Peterson, Barbara Koenig, and Susan Wolf
Disclosing genomic incidental findings in a cancer biobank: An ELSI experiment* R01
Seattle Children's Hospital Holly K. Tabor Innovative Approaches to Returning Results in Exome and Genome Sequencing Studies R01
Vanderbilt University Ellen Wright Clayton Returning research results of pediatric genomic research to participants R21

* Co-funded by NCI

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Working Groups

Informed Consent & Governance
Chairs: Paul Appelbaum and Joon-Ho Yu
Mission: Discuss emerging issues and develop new and creative approaches related to informed consent in the context of clinical sequencing; compare and, to the extent feasible, develop standardized consent language and protocols. Discuss and compile experience with institutional governance of genomic data in research and clinical settings; where appropriate integrate governance recommendations with best practice and/or model language for informed consent.

Actionable Variants and Return of Results
Chairs: Laura Amendola and Wendy Chung

  1. Define the principles and processes guiding the definition of an 'actionable' gene across the consortium, highlighting common outcomes and the rationale underlying discrepancies.
  2. Explore overlap regarding the classification process of identified variants in these actionable genes, and develop resources to support decisions with respect to pathogenicity.
  3. Coordinate with other CSER working groups to develop best practices for the process of returning genomic findings, including the informed consent process, analysis of sequence variants, storage in the medical record, and communication of results to the patient.

Sequencing Standards
Chair: Nick Wagle and Donna Muzny
Mission: Develop and share technical standards for sequencing in a clinical context (for example, minimum coverage and quality metrics, turnaround time, data formats, CLIA); develop best practices for variant validation.

Electronic Health Records
Chair: Peter Tarczy-Hornoch and Brian Shirts
Mission: Understand and facilitate cross site collaboration nationally around informatics work as related to variant annotation, prioritization, integration into electronic medical record, and integration into decision support.

Outcomes and Measures
Chairs: David Veenstra and Staci Gray
Mission: Coordinate development of instruments to measure psychosocial outcomes related to returning results.

Chairs: Kyle Brothers and Ben Wilfond
Mission: Explore and attempt to develop standardized approaches to addressing the unique ethical, legal, and practical challenges relating to returning results in studies involving pediatric populations.

Genetic Counseling
Chairs: Julia Wynn and Sarah Scollon
Mission: Discuss site-specific experiences with issues related to genetic counseling. Work on publications and educational materials, and function as a sounding board to new groups.

Chair: Will Parsons and Dan Robinson
Misson: Explore the unique technical, interpretive and ethical challenges and considerations involved in clinical sequencing of cancer genomes (e.g. identification of somatic variants) and to attempt to develop best practices for these tests.  

Practitioner Education
Chairs: Sharon Plon and Kelly East
Mission: Develop ideas, tools and resources that can help inform non-genetic medical practitioners of the use of genomic sequencing in the clinic. 

CSER Website 

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Meetings, Workshops and Webinars

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Program Contacts

NHGRI Program Directors

Lucia Hindorff, Ph.D., M.P.H.
Division of Genomic Medicine

Dave Kaufman, Ph.D.
Division of Genomics and Society

Jean McEwen, J.D., Ph.D.
Division of Genomics and Society

Carolyn Hutter, Ph.D.
Division of Genomic Medicine

NHGRI Program Analysts

Ellen Howerton 
Division of Genomic Medicine

Melpi Kasapi 
Division of Genomic Medicine

National Cancer Institute (NCI) Program Directors

Charlisse Caga-anan, J.D.

Kelly Filipski, Ph.D., M.P.H.

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Last Updated: February 2, 2017