2016
DOI: 10.1038/nbt.3520
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Abstract: High-throughput sequencing of circulating tumor DNA (ctDNA) promises to facilitate personalized cancer therapy. However, low quantities of cell-free DNA (cfDNA) in the blood and sequencing artifacts currently limit analytical sensitivity. To overcome these limitations, we introduce an approach for integrated digital error suppression (iDES). Our method combines in silico elimination of highly stereotypical background artifacts with a molecular barcoding strategy for the efficient recovery of cfDNA molecules. I… Show more

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Cited by 841 publications
(922 citation statements)
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“…This number can be measured by calculating the ratio of the detected individual molecules after sequencing to the total approximate number of DNA molecules that enter the assay. Over last five years, this metric improved from around 30% in 2011 (86) to more than 60% in 2016 (89).…”
Section: Error Suppression Methodsmentioning
confidence: 99%
See 1 more Smart Citation
“…This number can be measured by calculating the ratio of the detected individual molecules after sequencing to the total approximate number of DNA molecules that enter the assay. Over last five years, this metric improved from around 30% in 2011 (86) to more than 60% in 2016 (89).…”
Section: Error Suppression Methodsmentioning
confidence: 99%
“…In our own data, (Assouline and colleagues, in review) we have directly inferred mutations from ctDNA libraries using a similar error suppression strategy at levels as low as 1% across a broad gene panel. An interesting combination approach termed "integrated digital error suppression" (iDES) was described in 2016 by Newman and colleagues (89). The authors redesigned their previously published Capp-Seq panel (81) to integrate molecular barcoding into their workflow.…”
Section: Error Suppression Methodsmentioning
confidence: 99%
“…However, there is a paucity of cfDNA data sets large enough to evaluate the similarity of tumor-initiating alterations ("truncal drivers") in solid tumor cancers to those found in the cfDNA of advanced cancer patients. Among the various methods available for cfDNA analysis, targeted panel deep-sequencing assays that utilize extensive errorcorrection methods provide the depth (sensitivity) and genomic breadth necessary to optimally survey tumor-derived genomic alterations in plasma cfDNA, even at low allelic fractions (12)(13)(14)(15).…”
Section: Introductionmentioning
confidence: 99%
“…The same authors recently re-engineered their approach by combining a digital error suppression (iDES) technique to reduce background artifacts with a molecular barcoding strategy for the efficient recovery of cfDNA molecules. This combination of techniques resulted in a 15-fold improvement in respect to sensitivity [30]. This example shows that detection of unknown biomarkers within a screening procedure in stage 1 tumor patients is currently at the technical limits of known methods, and that only a combination of bioinformatics and sophisticated molecular techniques will solve this problem.…”
Section: Deep Sequencing-based Approaches/ Ngs-based Methodsmentioning
confidence: 93%