title: Performance comparison of whole-genome sequencing platforms.
abstract: 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.
authors.affiliation: Department of Genetics, Stanford University, Stanford, California, USA.
authors.forename: Hugo Y K
authors.initials: HY
authors.lastname: Lam
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Clark
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.forename: Rong
authors.initials: R
authors.lastname: Chen
authors.forename: Georges
authors.initials: G
authors.lastname: Natsoulis
authors.forename: Maeve
authors.initials: M
authors.lastname: O'Huallachain
authors.forename: Frederick E
authors.initials: FE
authors.lastname: Dewey
authors.forename: Lukas
authors.initials: L
authors.lastname: Habegger
authors.forename: Euan A
authors.initials: EA
authors.lastname: Ashley
authors.forename: Mark B
authors.initials: MB
authors.lastname: Gerstein
authors.forename: Atul J
authors.initials: AJ
authors.lastname: Butte
authors.forename: Hanlee P
authors.initials: HP
authors.lastname: Ji
authors.forename: Michael
authors.initials: M
authors.lastname: Snyder
mesh_terms: D021901:DNA, Intergenic / Q000235:genetics; D005091:Exons / Q000235:genetics; D015894:Genome, Human; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics; D007438:Introns / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012107:Research Design / Q000592:standards*; D020506:Untranslated Regions / Q000235:genetics
chemical_list: D021901:DNA, Intergenic; D020506:Untranslated Regions