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Achieving reproducibility and accuracy in cancer mutation detection with whole-genome and whole-exome sequencing

The Somatic Mutation Working Group of the SEQC-II Consortium
doi: https://doi.org/10.1101/626440
1Bioinformatics branch, Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079
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Abstract

Clinical applications of precision oncology require accurate tests that can distinguish tumor-specific mutations from errors introduced at each step of next generation sequencing (NGS). For NGS to successfully improve patient lives, discriminating between true mutations and artifacts is crucial.

We systematically interrogated somatic mutations in paired tumor-normal cell lines to identify factors affecting detection reproducibility and accuracy. Different types of samples with varying input amount and tumor purity were processed using multiple library construction protocols. Whole-genome and whole-exome sequencing were carried out at six sequencing centers followed by processing with nine bioinformatics pipelines to evaluate their reproducibility. We identified artifacts due to sample and library processing and evaluated the capabilities and limitations of bioinformatics tools for artifact detection and removal.

By examining the interaction and effect of various wet lab and computational parameters concomitantly, here we recommend actionable best practices for mutation detection in clinical applications using NGS technologies.

Footnotes

  • Correcting the title

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.
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Posted June 02, 2019.
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Achieving reproducibility and accuracy in cancer mutation detection with whole-genome and whole-exome sequencing
The Somatic Mutation Working Group of the SEQC-II Consortium
bioRxiv 626440; doi: https://doi.org/10.1101/626440
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Achieving reproducibility and accuracy in cancer mutation detection with whole-genome and whole-exome sequencing
The Somatic Mutation Working Group of the SEQC-II Consortium
bioRxiv 626440; doi: https://doi.org/10.1101/626440

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