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bioRxiv · 10.1101/179713

Accurate detection of low-level somatic mutations with technical replication for next-generation sequencing

Kim, J.·Kim, D.·Lim, J. S.·Maeng, J. H.·Son, H.·Kang, H.-C.·Nam, H.·Lee, J. H.·Kim, S.
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Abstract

Accurate genome-wide detection of somatic mutations with low variant allele frequency (VAF, <1%) has proven difficult, for which generalized, scalable methods are lacking. Herein, we describe a new computational method, called RePlow that we developed to detect low-VAF somatic mutations based on simple, library-level replicates for next-generation sequencing on any platform. Through joint analysis of replicates, RePlow is able to remove prevailing background errors in next-generation sequencing analysis, facilitating remarkable improvement in the detection accuracy for low-VAF somatic mutations (up to [~]99% reduction in false positives). The method was validated in independent cancer panel and brain tissue sequencing data. Our study suggests a new paradigm with which to exploit an overwhelming abundance of sequencing data for accurate variant detection.

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Kim, J., Kim, D., Lim, J. S., Maeng, J. H., Son, H., Kang, H.-C., Nam, H., Lee, J. H., Kim, S.. 2017-08-23. Accurate detection of low-level somatic mutations with technical replication for next-generation sequencing. https://doi.org/10.1101/179713

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