The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
Integrated digital error suppression for improved detection of circulating tumor DNA
Open accessAbstract
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. Individually, these two methods each improve the sensitivity of cancer personalized profiling by deep sequencing (CAPP-Seq) by about threefold, and synergize when combined to yield ∼15-fold improvements. As a result, iDES-enhanced CAPP-Seq facilitates noninvasive variant detection across hundreds of kilobases. Applied to non-small cell lung cancer (NSCLC) patients, our method enabled biopsy-free profiling of EGFR kinase domain mutations with 92% sensitivity and >99.99% specificity at the variant level, and with 90% sensitivity and 96% specificity at the patient level. In addition, our approach allowed monitoring of NSCLC ctDNA down to 4 in 105 cfDNA molecules. We anticipate that iDES will aid the noninvasive genotyping and detection of ctDNA in research and clinical settings.
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Cites
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Metadata
- Authors
- Newman, A. M., Lovejoy, A. F., Klass, D. M., Kurtz, D. M., Chabon, J. J., Scherer, F., Stehr, H., Liu, C. L., Bratman, S. V., Say, C., Zhou, L., Carter, J. N., West, R. B., Sledge Jr, G. W., Shrager, J. B., Loo, B. W., Neal, J. W., Wakelee, H. A., Diehn, M., & Alizadeh, A. A.
- Venue
- Nature Biotechnology
- Published
- 2016-03-28
- Volume
- 34
- Issue
- 5
- Pages
- 547-555
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W2329906190
- Cited by
- 1,099
- References
- 16
- FWCI
- 40.76
- Type
- journal article
- Language
- en
- Open access
- green
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- Newman, A. M., Lovejoy, A. F., Klass, D. M., Kurtz, D. M., Chabon, J. J., Scherer, F., Stehr, H., Liu, C. L., Bratman, S. V., Say, C., Zhou, L., Carter, J. N., West, R. B., Sledge Jr, G. W., Shrager, J. B., Loo, B. W., Neal, J. W., Wakelee, H. A., Diehn, M., & Alizadeh, A. A. (2016). Integrated digital error suppression for improved detection of circulating tumor DNA. Nature Biotechnology. https://doi.org/10.1038/nbt.3520
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
