Format

Send to

Choose Destination
Genet Med. 2018 Aug;20(8):855-866. doi: 10.1038/gim.2017.192. Epub 2017 Nov 16.

Characterizing reduced coverage regions through comparison of exome and genome sequencing data across 10 centers.

Author information

1
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
2
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
3
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, Cambridge, Massachusetts, USA.
4
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
5
UW Medicine Center for Precision Diagnostics, and Department of Pathology, University of Washington, Seattle, Washington, USA.
6
Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
7
Department of Pathology, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
8
Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
9
Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
10
Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
11
HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA.
12
Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
13
Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
14
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
15
Renaissance Computing Institute, Chapel Hill, North Carolina, USA.
16
Division of Genomic Medicine, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
17
Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
18
Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
19
Center for Cancer Precision Medicine and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
20
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
21
Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
22
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA. donnam@bcm.edu.
23
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. nikhil_wagle@dfci.harvard.edu.
24
Center for Cancer Precision Medicine and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. nikhil_wagle@dfci.harvard.edu.
25
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. nikhil_wagle@dfci.harvard.edu.

Abstract

PURPOSE:

As massively parallel sequencing is increasingly being used for clinical decision making, it has become critical to understand parameters that affect sequencing quality and to establish methods for measuring and reporting clinical sequencing standards. In this report, we propose a definition for reduced coverage regions and describe a set of standards for variant calling in clinical sequencing applications.

METHODS:

To enable sequencing centers to assess the regions of poor sequencing quality in their own data, we optimized and used a tool (ExCID) to identify reduced coverage loci within genes or regions of particular interest. We used this framework to examine sequencing data from 500 patients generated in 10 projects at sequencing centers in the National Human Genome Research Institute/National Cancer Institute Clinical Sequencing Exploratory Research Consortium.

RESULTS:

This approach identified reduced coverage regions in clinically relevant genes, including known clinically relevant loci that were uniquely missed at individual centers, in multiple centers, and in all centers.

CONCLUSION:

This report provides a process road map for clinical sequencing centers looking to perform similar analyses on their data.

KEYWORDS:

clinical sequencing; exome; genome; sequencing standards

PMID:
29144510
PMCID:
PMC6456263
DOI:
10.1038/gim.2017.192
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center