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Nucleic Acids Res. 2015 Jun 23;43(11):e76. doi: 10.1093/nar/gkv216. Epub 2015 Mar 27.

New insights into the performance of human whole-exome capture platforms.

Author information

1
Center for Cardiovascular Genetics and Gene Diagnostics, Foundation for People with Rare Diseases, Schlieren-Zurich CH-8952, Switzerland.
2
Department of Clinical Research, University of Berne, Berne CH-3010, Switzerland.
3
Functional Genomics Center Zurich, Zurich CH-8057, Switzerland Division of Scientific IT Services, ETH Zurich, Zurich CH-8092, Switzerland.
4
Functional Genomics Center Zurich, Zurich CH-8057, Switzerland.
5
Division of Medical Genetics, Center for Laboratory Medicine, Aarau CH-5001, Switzerland.
6
Sophia Genetics SA, Lausanne CH-1015, Switzerland.
7
Division of Metabolism, University Children's Hospital, Zurich CH-8032, Switzerland.
8
Department of Cardiovascular Surgery, University Hospital, Berne CH-3010, Switzerland.
9
Interfaculty Bioinformatics Unit and Swiss Institute of Bioinformatics, University of Berne, Berne CH-3012, Switzerland.
10
Center for Cardiovascular Genetics and Gene Diagnostics, Foundation for People with Rare Diseases, Schlieren-Zurich CH-8952, Switzerland Department of Cardiovascular Surgery, University Hospital, Berne CH-3010, Switzerland Zurich Center for Integrative Human Physiology, University of Zurich, Zurich CH-8057, Switzerland matyas@genetikzentrum.ch.

Abstract

Whole exome sequencing (WES) is increasingly used in research and diagnostics. WES users expect coverage of the entire coding region of known genes as well as sufficient read depth for the covered regions. It is, however, unknown which recent WES platform is most suitable to meet these expectations. We present insights into the performance of the most recent standard exome enrichment platforms from Agilent, NimbleGen and Illumina applied to six different DNA samples by two sequencing vendors per platform. Our results suggest that both Agilent and NimbleGen overall perform better than Illumina and that the high enrichment performance of Agilent is stable among samples and between vendors, whereas NimbleGen is only able to achieve vendor- and sample-specific best exome coverage. Moreover, the recent Agilent platform overall captures more coding exons with sufficient read depth than NimbleGen and Illumina. Due to considerable gaps in effective exome coverage, however, the three platforms cannot capture all known coding exons alone or in combination, requiring improvement. Our data emphasize the importance of evaluation of updated platform versions and suggest that enrichment-free whole genome sequencing can overcome the limitations of WES in sufficiently covering coding exons, especially GC-rich regions, and in characterizing structural variants.

PMID:
25820422
PMCID:
PMC4477645
DOI:
10.1093/nar/gkv216
[Indexed for MEDLINE]
Free PMC Article

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