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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9522828/ https://www.ncbi.nlm.nih.gov/pubmed/36175411 http://dx.doi.org/10.1038/s41467-022-32995-6 |
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author | 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 French, Samuel Magyar, Clara E. Dry, Sarah Lajonchere, Clara Geschwind, Daniel Choi, Gina Saab, Sammy Alber, Frank Wong, Wing Hung Dubinett, Steven M. Aberle, Denise R. Agopian, Vatche Han, Steven-Huy B. Ni, Xiaohui Li, Wenyuan Zhou, Xianghong Jasmine |
author_facet | 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 French, Samuel Magyar, Clara E. Dry, Sarah Lajonchere, Clara Geschwind, Daniel Choi, Gina Saab, Sammy Alber, Frank Wong, Wing Hung Dubinett, Steven M. Aberle, Denise R. Agopian, Vatche Han, Steven-Huy B. Ni, Xiaohui Li, Wenyuan Zhou, Xianghong Jasmine |
author_sort | Stackpole, Mary L. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9522828 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-95228282022-10-01 Cost-effective methylome sequencing of cell-free DNA for accurately detecting and locating cancer 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 French, Samuel Magyar, Clara E. Dry, Sarah Lajonchere, Clara Geschwind, Daniel Choi, Gina Saab, Sammy Alber, Frank Wong, Wing Hung Dubinett, Steven M. Aberle, Denise R. Agopian, Vatche Han, Steven-Huy B. Ni, Xiaohui Li, Wenyuan Zhou, Xianghong Jasmine Nat Commun Article 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. Nature Publishing Group UK 2022-09-29 /pmc/articles/PMC9522828/ /pubmed/36175411 http://dx.doi.org/10.1038/s41467-022-32995-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article 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 French, Samuel Magyar, Clara E. Dry, Sarah Lajonchere, Clara Geschwind, Daniel Choi, Gina Saab, Sammy Alber, Frank Wong, Wing Hung Dubinett, Steven M. Aberle, Denise R. Agopian, Vatche Han, Steven-Huy B. Ni, Xiaohui Li, Wenyuan Zhou, Xianghong Jasmine Cost-effective methylome sequencing of cell-free DNA for accurately detecting and locating cancer |
title | Cost-effective methylome sequencing of cell-free DNA for accurately detecting and locating cancer |
title_full | Cost-effective methylome sequencing of cell-free DNA for accurately detecting and locating cancer |
title_fullStr | Cost-effective methylome sequencing of cell-free DNA for accurately detecting and locating cancer |
title_full_unstemmed | Cost-effective methylome sequencing of cell-free DNA for accurately detecting and locating cancer |
title_short | Cost-effective methylome sequencing of cell-free DNA for accurately detecting and locating cancer |
title_sort | cost-effective methylome sequencing of cell-free dna for accurately detecting and locating cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9522828/ https://www.ncbi.nlm.nih.gov/pubmed/36175411 http://dx.doi.org/10.1038/s41467-022-32995-6 |
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