Cost-effective methylome sequencing of cell-free DNA for accurately detecting and locating cancer
Early 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 con...
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| Published in | Nature communications Vol. 13; no. 1; p. 5566 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
29.09.2022
Nature Publishing Group Nature Portfolio |
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| Abstract | Early 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.
Early cancer detection by cell-free DNA (cfDNA) is challenged by the low amount of tumour DNA in cfDNA, tumour heterogeneity and the small patient cohorts. Here, the authors develop a method, cfMethyl-Seq, for cost-effective methylome profiling of cfDNA and for detecting and locating cancer. |
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| AbstractList | Early 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.
Early cancer detection by cell-free DNA (cfDNA) is challenged by the low amount of tumour DNA in cfDNA, tumour heterogeneity and the small patient cohorts. Here, the authors develop a method, cfMethyl-Seq, for cost-effective methylome profiling of cfDNA and for detecting and locating cancer. Abstract Early 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. Early 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.Early cancer detection by cell-free DNA (cfDNA) is challenged by the low amount of tumour DNA in cfDNA, tumour heterogeneity and the small patient cohorts. Here, the authors develop a method, cfMethyl-Seq, for cost-effective methylome profiling of cfDNA and for detecting and locating cancer. Early 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. Abstract Early 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. |
| ArticleNumber | 5566 |
| Author | Stackpole, Mary L. Tomlinson, James S. He, Shanshan Yuan, Zuyang Wong, Wing Hung Han, Steven-Huy B. Lee, Yi-Te Saab, Sammy Tran, Benjamin Li, Wenyuan Li, Qingjiao Choi, Gina Dry, Sarah Aberle, Denise R. French, Samuel Tseng, Hsian-Rong Noor, Zorawar Li, Paul Shize Zeng, Weihua Geschwind, Daniel Li, Shuo Magyar, Clara E. Yildirim, Asli Alber, Frank Sun, Fengzhu Lajonchere, Clara Zhou, Xianghong Jasmine Zhou, Yonggang Ahuja, Preeti Chen, Pin-Jung Dubinett, Steven M. Liu, Chun-Chi Garon, Edward Agopian, Vatche Zhu, Yazhen Yokomizo, Megumi Wang, Ziye Ni, Xiaohui Yeh, Angela Winograd, Paul |
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| References | Zeybel (CR12) 2012; 18 Liu (CR2) 2020; 31 Li (CR7) 2018; 46 CR18 Grossman (CR15) 2016; 375 Liberzon (CR17) 2011; 27 Chan (CR19) 2013; 110 Krueger, Andrews (CR11) 2011; 27 Pedregosa (CR29) 2011; 12 Hardy (CR14) 2017; 66 Kang (CR8) 2017; 18 Angulo (CR13) 2015; 149 Shen (CR6) 2018; 563 de Koker, van Paemel, de Wilde, de Preter, Callewaert (CR21) 2019 Shen, Burgener, Bratman, De Carvalho (CR23) 2019; 14 CR5 Guo (CR4) 2017; 49 CR28 CR9 CR27 CR26 Liang (CR10) 2021; 5 CR24 Cristiano (CR3) 2019; 570 Kennedy (CR25) 2014; 9 CR20 Cohen (CR1) 2018; 359 Liberzon (CR16) 2015; 1 Chabon (CR22) 2020; 580 38693151 - Nat Commun. 2024 May 1;15(1):3693 F Krueger (32995_CR11) 2011; 27 32995_CR5 32995_CR20 MC Liu (32995_CR2) 2020; 31 32995_CR24 32995_CR26 32995_CR27 32995_CR28 KCA Chan (32995_CR19) 2013; 110 W Li (32995_CR7) 2018; 46 SR Kennedy (32995_CR25) 2014; 9 A Liberzon (32995_CR16) 2015; 1 N Liang (32995_CR10) 2021; 5 A de Koker (32995_CR21) 2019 S Kang (32995_CR8) 2017; 18 SY Shen (32995_CR23) 2019; 14 M Zeybel (32995_CR12) 2012; 18 SY Shen (32995_CR6) 2018; 563 A Liberzon (32995_CR17) 2011; 27 JD Cohen (32995_CR1) 2018; 359 T Hardy (32995_CR14) 2017; 66 S Cristiano (32995_CR3) 2019; 570 32995_CR18 S Guo (32995_CR4) 2017; 49 JJ Chabon (32995_CR22) 2020; 580 32995_CR9 F Pedregosa (32995_CR29) 2011; 12 P Angulo (32995_CR13) 2015; 149 RL Grossman (32995_CR15) 2016; 375 |
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| Snippet | Early cancer detection by cell-free DNA faces multiple challenges: low fraction of tumor cell-free DNA, molecular heterogeneity of cancer, and sample sizes... Abstract Early cancer detection by cell-free DNA faces multiple challenges: low fraction of tumor cell-free DNA, molecular heterogeneity of cancer, and sample... Abstract Early cancer detection by cell-free DNA faces multiple challenges: low fraction of tumor cell-free DNA, molecular heterogeneity of cancer, and sample... |
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| Title | Cost-effective methylome sequencing of cell-free DNA for accurately detecting and locating cancer |
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