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.
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Change history
07 June 2012
In the version of this article initially published, the accession code to obtain raw sequence data was given as SRA045736.2; the correct code is SRA045736. The error has been corrected in the HTML and PDF versions of the article.
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Acknowledgements
This work is supported by the Stanford Department of Genetics and the US National Institutes of Health.
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H.Y.K.L. and M.J.C. did the analysis. G.N. and L.H. assisted in the analysis. Rui C. did DNA sequencing. Rong C. did the disease-association study. Rui C. and M.O'H. did the validation experiments. H.Y.K.L., F.E.D., E.A.A., M.B.G., A.J.B., H.P.J. and M.S. coordinated the analysis and revised the manuscript. H.Y.K.L., M.J.C. and M.S. wrote the manuscript.
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Competing interests
M.S. is a scientific advisory board member for Genapsys, Inc.; a scientific advisory board member and cofounder of Personalis, Inc.; and a consultant for Illumina.
Supplementary information
Supplementary Text and Figures
Supplementary Figures 1 and 2 (PDF 1129 kb)
Supplementary Table 1
Disease association of all platform-specific SNPs. (XLSX 40 kb)
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Lam, H., Clark, M., Chen, R. et al. Performance comparison of whole-genome sequencing platforms. Nat Biotechnol 30, 78–82 (2012). https://doi.org/10.1038/nbt.2065
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DOI: https://doi.org/10.1038/nbt.2065
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