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Performance comparison of whole-genome sequencing platforms

Source: Nature Biotechnol. 30, 78 (2012); http://dx.doi.org/10.1038/nbt.2065

Issue Date: 15 January 2012

PUBLICATION DATA
ISSN:
1553-9628 (online)
Publisher:
AIP is a member of CrossRef NATURE
Hugo Y K Lam
1] Department of Genetics, Stanford University, Stanford, California, USA. [2] Personalis, Inc., Palo Alto, California, USA.

Michael J Clark
Department of Genetics, Stanford University, Stanford, California, USA.

Rui Chen
Department of Genetics, Stanford University, Stanford, California, USA.

Rong Chen
1] Division of Systems Medicine, Department of Pediatrics, Stanford University, Stanford, California, USA. [2] Personalis, Inc., Palo Alto, California, USA.

Georges Natsoulis
Department of Medicine, Stanford University, Stanford, California, USA.

Maeve O'Huallachain
Department of Genetics, Stanford University, Stanford, California, USA.

Frederick E Dewey
Center for Inherited Cardiovascular Disease, Division of Cardiovascular Medicine, Stanford University, Stanford, California, USA.

Lukas Habegger
Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut, USA.

Euan A Ashley
Center for Inherited Cardiovascular Disease, Division of Cardiovascular Medicine, Stanford University, Stanford, California, USA.

Mark B Gerstein
1] Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut, USA. [2] Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA. [3] Department of Computer Science, Yale University, New Haven, Connecticut, USA.

Atul J Butte
Division of Systems Medicine, Department of Pediatrics, Stanford University, Stanford, California, USA.

Hanlee P Ji
Department of Medicine, Stanford University, Stanford, California, USA.

Michael Snyder
Department of Genetics, Stanford University, Stanford, California, USA.
Whole-genome sequencing is becoming commonplace, but the accuracy and completeness of variant calling by the most widely used platforms from Illumina and Complete Genomics have not been reported. Here we sequenced the genome of an individual with both technologies to a high average coverage of 76, and compared their performance with respect to sequence coverage and calling of single-nucleotide variants (SNVs), insertions and deletions (indels). Although 88.1% of the 3.7 million unique SNVs were concordant between platforms, there were tens of thousands of platform-specific calls located in genes and other genomic regions. In contrast, 26.5% of indels were concordant between platforms. Target enrichment validated 92.7% of the concordant SNVs, whereas validation by genotyping array revealed a sensitivity of 99.3%. The validation experiments also suggested that >60% of the platform-specific variants were indeed present in the genome. Our results have important implications for understanding the accuracy and completeness of the genome sequencing platforms. ©2011

(As supplied by publisher.)

Digital Object Identifier: http://dx.doi.org/10.1038/nbt.2065
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