Debra Leonard and colleagues: Standards for Clinical Grade Genomic Databases

Sophia L. Yohe, Alexis B. Carter, John D. Pfeifer, James M. Crawford, Allison Cushman-Vokoun, Samuel Caughron, and Debra G. B. Leonard (2015) Standards for Clinical Grade Genomic Databases. Archives of Pathology & Laboratory Medicine: November 2015, Vol. 139, No. 11, pp. 1400-1412.

CAP LABORATORY IMPROVEMENT PROGRAMS

Standards for Clinical Grade Genomic Databases

Sophia L. Yohe, MD; Alexis B. Carter, MD; John D. Pfeifer, MD, PhD; James M. Crawford, MD, PhD; Allison Cushman-Vokoun, MD, PhD; Samuel Caughron, MD; Debra G. B. Leonard, MD, PhD

From the Department of Laboratory Medicine and Pathology, University of Minnesota Medical Center, Minneapolis (Dr Yohe); the Department of Pathology and Laboratory Medicine and the Department of Biomedical Informatics, Emory University, Atlanta, Georgia (Dr Carter); the Department of Pathology, Washington University School of Medicine, St. Louis, Missouri (Dr Pfeifer); the Department of Pathology and Laboratory Medicine, Hofstra North Shore–Long Island Jewish School of Medicine, Hempstead, New York (Dr Crawford); the Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha (Dr Cushman-Vokoun); the MAWD Pathology Group, North Kansas City, Missouri (Dr Caughron); and the Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington (Dr Leonard).

Reprints: Sophia L. Yohe, MD, Department of Laboratory Medicine and Pathology, University of Minnesota Medical Center, MMC 609 Mayo Bldg, 420 Delaware St SE, Minneapolis, MN 55455 (e-mail: yohe0001@umn.edu).

The authors have no relevant financial interest in the products or companies described in this article.

Supplemental digital content is available for this article at www.archivesofpathology.org in the November 2015 table of contents.

Context.— Next-generation sequencing performed in a clinical environment must meet clinical standards, which requires reproducibility of all aspects of the testing. Clinical-grade genomic databases (CGGDs) are required to classify a variant and to assist in the professional interpretation of clinical next-generation sequencing. Applying quality laboratory standards to the reference databases used for sequence-variant interpretation presents a new challenge for validation and curation.

Objectives.— To define CGGD and the categories of information contained in CGGDs and to frame recommendations for the structure and use of these databases in clinical patient care.

Design.— Members of the College of American Pathologists Personalized Health Care Committee reviewed the literature and existing state of genomic databases and developed a framework for guiding CGGD development in the future.

Results.— Clinical-grade genomic databases may provide different types of information. This work group defined 3 layers of information in CGGDs: clinical genomic variant repositories, genomic medical data repositories, and genomic medicine evidence databases. The layers are differentiated by the types of genomic and medical information contained and the utility in assisting with clinical interpretation of genomic variants. Clinical-grade genomic databases must meet specific standards regarding submission, curation, and retrieval of data, as well as the maintenance of privacy and security.

Conclusion.— These organizing principles for CGGDs should serve as a foundation for future development of specific standards that support the use of such databases for patient care.