Abstract
Next-generation sequencing (NGS) will likely facilitate a better understanding of the causes and consequences of human genetic variability. In this context, the validity of NGS-inferred single-nucleotide variants (SNVs) is of paramount importance. We therefore developed a statistical framework to assess the fidelity of three common NGS platforms. Using aligned DNA sequence data from two completely sequenced HapMap samples as included in the 1000 Genomes Project, we unraveled remarkably different error profiles for the three platforms. Compared to confirmed HapMap variants, newly identified SNVs included a substantial proportion of false positives (3–17%). Consensus calling by more than one platform yielded significantly lower error rates (1–4%). This implies that the use of multiple NGS platforms may be more cost-efficient than relying upon a single technology alone, particularly in physically localized sequencing experiments that rely upon small error rates. Our study thus highlights that different NGS platforms suit different practical applications differently well, and that NGS-based studies require stringent data quality control for their results to be valid.
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Acknowledgments
This work was supported by the German National Genome Research Network (NGFNplus; 01GS08182) through the Colon Cancer Network (CCN) and by the German Research Foundation (DFG) excellence cluster ‘‘Inflammation at Interfaces’’. None of the funding organizations had any influence on the design, conduct, or conclusions of the study. The authors declare no competing financial interests.
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M. Nothnagel and A. Herrmann contributed equally to this work.
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Nothnagel, M., Herrmann, A., Wolf, A. et al. Technology-specific error signatures in the 1000 Genomes Project data. Hum Genet 130, 505–516 (2011). https://doi.org/10.1007/s00439-011-0971-3
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DOI: https://doi.org/10.1007/s00439-011-0971-3