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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
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.
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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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