title: New insights into the performance of human whole-exome capture platforms.
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.
authors.affiliation: Center for Cardiovascular Genetics and Gene Diagnostics, Foundation for People with Rare Diseases, Schlieren-Zurich CH-8952, Switzerland.
authors.forename: Janine
authors.initials: J
authors.lastname: Meienberg
authors.affiliation: Center for Cardiovascular Genetics and Gene Diagnostics, Foundation for People with Rare Diseases, Schlieren-Zurich CH-8952, Switzerland.
authors.forename: Katja
authors.initials: K
authors.lastname: Zerjavic
authors.affiliation: Department of Clinical Research, University of Berne, Berne CH-3010, Switzerland.
authors.forename: Irene
authors.initials: I
authors.lastname: Keller
authors.affiliation: Functional Genomics Center Zurich, Zurich CH-8057, Switzerland Division of Scientific IT Services, ETH Zurich, Zurich CH-8092, Switzerland.
authors.forename: Michal
authors.initials: M
authors.lastname: Okoniewski
authors.affiliation: Functional Genomics Center Zurich, Zurich CH-8057, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Patrignani
authors.affiliation: Division of Medical Genetics, Center for Laboratory Medicine, Aarau CH-5001, Switzerland.
authors.forename: Katja
authors.initials: K
authors.lastname: Ludin
authors.affiliation: Sophia Genetics SA, Lausanne CH-1015, Switzerland.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Division of Metabolism, University Children's Hospital, Zurich CH-8032, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Steinmann
authors.affiliation: Department of Cardiovascular Surgery, University Hospital, Berne CH-3010, Switzerland.
authors.forename: Thierry
authors.initials: T
authors.lastname: Carrel
authors.affiliation: Division of Medical Genetics, Center for Laboratory Medicine, Aarau CH-5001, Switzerland.
authors.forename: Benno
authors.initials: B
authors.lastname: Röthlisberger
authors.affiliation: Functional Genomics Center Zurich, Zurich CH-8057, Switzerland.
authors.forename: Ralph
authors.initials: R
authors.lastname: Schlapbach
authors.affiliation: Interfaculty Bioinformatics Unit and Swiss Institute of Bioinformatics, University of Berne, Berne CH-3012, Switzerland.
authors.forename: Rémy
authors.initials: R
authors.lastname: Bruggmann
authors.affiliation: 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.
authors.forename: Gabor
authors.initials: G
authors.lastname: Matyas
mesh_terms: D000483:Alleles; D001482:Base Composition; D004247:DNA / Q000737:chemistry; D059472:Exome; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D004247:DNA
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