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Stackpole, Mary L.; Zeng, Weihua; Li, Shuo; Liu, Chun-Chi; Zhou, Yonggang; He, Shanshan; Yeh, Angela; Wang, Ziye; Sun, Fengzhu; Li, Qingjiao; Yuan, Zuyang; Yildirim, Asli; Chen, Pin-Jung; Winograd, Paul; Tran, Benjamin; Lee, Yi-Te; Li, Paul Shize; Noor, Zorawar; Yokomizo, Megumi; Ahuja, Preeti; Zhu, Yazhen; Tseng, Hsian-Rong; Tomlinson, James S.; Garon, Edward; [...]

Cost-effective methylome sequencing of cell-free DNA for accurately detecting and locating cancer

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  • Media type: E-Article
  • Title: Cost-effective methylome sequencing of cell-free DNA for accurately detecting and locating cancer
  • Contributor: Stackpole, Mary L.; Zeng, Weihua; Li, Shuo; Liu, Chun-Chi; Zhou, Yonggang; He, Shanshan; Yeh, Angela; Wang, Ziye; Sun, Fengzhu; Li, Qingjiao; Yuan, Zuyang; Yildirim, Asli; Chen, Pin-Jung; Winograd, Paul; Tran, Benjamin; Lee, Yi-Te; Li, Paul Shize; Noor, Zorawar; Yokomizo, Megumi; Ahuja, Preeti; Zhu, Yazhen; Tseng, Hsian-Rong; Tomlinson, James S.; Garon, Edward; [...]
  • Published: Springer Science and Business Media LLC, 2022
  • Published in: Nature Communications, 13 (2022) 1
  • Language: English
  • DOI: 10.1038/s41467-022-32995-6
  • ISSN: 2041-1723
  • Origination:
  • Footnote:
  • Description: AbstractEarly cancer detection by cell-free DNA faces multiple challenges: low fraction of tumor cell-free DNA, molecular heterogeneity of cancer, and sample sizes that are not sufficient to reflect diverse patient populations. Here, we develop a cancer detection approach to address these challenges. It consists of an assay, cfMethyl-Seq, for cost-effective sequencing of the cell-free DNA methylome (with > 12-fold enrichment over whole genome bisulfite sequencing in CpG islands), and a computational method to extract methylation information and diagnose patients. Applying our approach to 408 colon, liver, lung, and stomach cancer patients and controls, at 97.9% specificity we achieve 80.7% and 74.5% sensitivity in detecting all-stage and early-stage cancer, and 89.1% and 85.0% accuracy for locating tissue-of-origin of all-stage and early-stage cancer, respectively. Our approach cost-effectively retains methylome profiles of cancer abnormalities, allowing us to learn new features and expand to other cancer types as training cohorts grow.
  • Access State: Open Access