In silico error correction improves cfDNA mutation calling

Kim, C. S., Mohan, S., Ayub, M., Rothwell, D. G., Dive, C., Brady, G. and Miller, C. (2018) In silico error correction improves cfDNA mutation calling. Bioinformatics, 35(14), pp. 2380-2385. (doi: 10.1093/bioinformatics/bty1004) (PMID:30520956) (PMCID:PMC6612818)

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Motivation: Circulating-free DNA (cfDNA) profiling by sequencing is an important minimally invasive protocol for monitoring the mutation profile of solid tumours in cancer patients. Since the concentration of available cfDNA is limited, sample library generation relies on multiple rounds of PCR amplification, during which the accumulation of errors results in reduced sensitivity and lower accuracy. Results: We present PCR Error Correction (PEC), an algorithm to identify and correct errors in short read sequencing data. It exploits the redundancy that arises from multiple rounds of PCR amplification. PEC is particularly well suited to applications such as single-cell sequencing and circulating tumour DNA (ctDNA) analysis, in which many cycles of PCR are used to generate sufficient DNA for sequencing from small amounts of starting material. When applied to ctDNA analysis, PEC significantly improves mutation calling accuracy, achieving similar levels of performance to more complex strategies that require additional protocol steps and access to calibration DNA datasets. Availability and implementation: PEC is available under the GPL-v3 Open Source licence, and is freely available from:

Item Type:Articles
Additional Information:This work was supported by Cancer Research UK via core funding to Cancer Research UK Manchester Institute (C5759/A20971), and funding to the Medical Research Council Manchester Single Cell Research Centre (MR/M008908/1 to CSK) and AstraZeneca (D1330N00013 to SM).
Glasgow Author(s) Enlighten ID:Miller, Professor Crispin
Authors: Kim, C. S., Mohan, S., Ayub, M., Rothwell, D. G., Dive, C., Brady, G., and Miller, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Bioinformatics
Publisher:Oxford University Press
ISSN (Online):1460-2059
Copyright Holders:Copyright © The Author(s) 2018
First Published:First published in Bioinformatics 35:2380–2385
Publisher Policy:Reproduced under a Creative Commons Licence

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