IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-35320-3.html
   My bibliography  Save this article

Tumor fractions deciphered from circulating cell-free DNA methylation for cancer early diagnosis

Author

Listed:
  • Xiao Zhou

    (Tsinghua University)

  • Zhen Cheng

    (Tsinghua University)

  • Mingyu Dong

    (Tsinghua University)

  • Qi Liu

    (Tsinghua University)

  • Weiyang Yang

    (Tsinghua University)

  • Min Liu

    (Tsinghua University
    Guangdong Second Provincial General Hospital)

  • Junzhang Tian

    (Guangdong Second Provincial General Hospital)

  • Weibin Cheng

    (Guangdong Second Provincial General Hospital)

Abstract

Tumor-derived circulating cell-free DNA (cfDNA) provides critical clues for cancer early diagnosis, yet it often suffers from low sensitivity. Here, we present a cancer early diagnosis approach using tumor fractions deciphered from circulating cfDNA methylation signatures. We show that the estimated fractions of tumor-derived cfDNA from cancer patients increase significantly as cancer progresses in two independent datasets. Employing the predicted tumor fractions, we establish a Bayesian diagnostic model in which training samples are only derived from late-stage patients and healthy individuals. When validated on early-stage patients and healthy individuals, this model exhibits a sensitivity of 86.1% for cancer early detection and an average accuracy of 76.9% for tumor localization at a specificity of 94.7%. By highlighting the potential of tumor fractions on cancer early diagnosis, our approach can be further applied to cancer screening and tumor progression monitoring.

Suggested Citation

  • Xiao Zhou & Zhen Cheng & Mingyu Dong & Qi Liu & Weiyang Yang & Min Liu & Junzhang Tian & Weibin Cheng, 2022. "Tumor fractions deciphered from circulating cell-free DNA methylation for cancer early diagnosis," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35320-3
    DOI: 10.1038/s41467-022-35320-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-35320-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-35320-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Viktor A. Adalsteinsson & Gavin Ha & Samuel S. Freeman & Atish D. Choudhury & Daniel G. Stover & Heather A. Parsons & Gregory Gydush & Sarah C. Reed & Denisse Rotem & Justin Rhoades & Denis Loginov & , 2017. "Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    2. Daniel D. Lee & H. Sebastian Seung, 1999. "Learning the parts of objects by non-negative matrix factorization," Nature, Nature, vol. 401(6755), pages 788-791, October.
    3. Christa Caggiano & Barbara Celona & Fleur Garton & Joel Mefford & Brian L. Black & Robert Henderson & Catherine Lomen-Hoerth & Andrew Dahl & Noah Zaitlen, 2021. "Comprehensive cell type decomposition of circulating cell-free DNA with CelFiE," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    4. Xingdong Chen & Jeffrey Gole & Athurva Gore & Qiye He & Ming Lu & Jun Min & Ziyu Yuan & Xiaorong Yang & Yanfeng Jiang & Tiejun Zhang & Chen Suo & Xiaojie Li & Lei Cheng & Zhenhua Zhang & Hongyu Niu & , 2020. "Non-invasive early detection of cancer four years before conventional diagnosis using a blood test," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    5. Jacob J. Chabon & Emily G. Hamilton & David M. Kurtz & Mohammad S. Esfahani & Everett J. Moding & Henning Stehr & Joseph Schroers-Martin & Barzin Y. Nabet & Binbin Chen & Aadel A. Chaudhuri & Chih Lon, 2020. "Integrating genomic features for non-invasive early lung cancer detection," Nature, Nature, vol. 580(7802), pages 245-251, April.
    6. Joshua Moss & Judith Magenheim & Daniel Neiman & Hai Zemmour & Netanel Loyfer & Amit Korach & Yaacov Samet & Myriam Maoz & Henrik Druid & Peter Arner & Keng-Yeh Fu & Endre Kiss & Kirsty L. Spalding & , 2018. "Comprehensive human cell-type methylation atlas reveals origins of circulating cell-free DNA in health and disease," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    7. Xuran Wang & Jihwan Park & Katalin Susztak & Nancy R. Zhang & Mingyao Li, 2019. "Bulk tissue cell type deconvolution with multi-subject single-cell expression reference," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Jonathan C. M. Wan & Dennis Stephens & Lingqi Luo & James R. White & Caitlin M. Stewart & Benoît Rousseau & Dana W. Y. Tsui & Luis A. Diaz, 2022. "Genome-wide mutational signatures in low-coverage whole genome sequencing of cell-free DNA," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Kate E. Stanley & Tatjana Jatsenko & Stefania Tuveri & Dhanya Sudhakaran & Lore Lannoo & Kristel Calsteren & Marie Borre & Ilse Parijs & Leen Coillie & Kris Bogaert & Rodrigo Almeida Toledo & Liesbeth, 2024. "Cell type signatures in cell-free DNA fragmentation profiles reveal disease biology," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. Yaping Liu & Sarah C. Reed & Christopher Lo & Atish D. Choudhury & Heather A. Parsons & Daniel G. Stover & Gavin Ha & Gregory Gydush & Justin Rhoades & Denisse Rotem & Samuel Freeman & David W. Katz &, 2024. "FinaleMe: Predicting DNA methylation by the fragmentation patterns of plasma cell-free DNA," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    4. Nicolette M. Fonseca & Corinne Maurice-Dror & Cameron Herberts & Wilson Tu & William Fan & Andrew J. Murtha & Catarina Kollmannsberger & Edmond M. Kwan & Karan Parekh & Elena Schönlau & Cecily Q. Bern, 2024. "Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    5. Alicia-Marie Conway & Simon P. Pearce & Alexandra Clipson & Steven M. Hill & Francesca Chemi & Dan Slane-Tan & Saba Ferdous & A. S. Md Mukarram Hossain & Katarzyna Kamieniecka & Daniel J. White & Clai, 2024. "A cfDNA methylation-based tissue-of-origin classifier for cancers of unknown primary," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    6. Mary L. Stackpole & Weihua Zeng & Shuo Li & Chun-Chi Liu & Yonggang Zhou & Shanshan He & Angela Yeh & Ziye Wang & Fengzhu Sun & Qingjiao Li & Zuyang Yuan & Asli Yildirim & Pin-Jung Chen & Paul Winogra, 2022. "Cost-effective methylome sequencing of cell-free DNA for accurately detecting and locating cancer," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    7. Tiantian Wang & Peilong Li & Qiuchen Qi & Shujun Zhang & Yan Xie & Jing Wang & Shibiao Liu & Suhong Ma & Shijun Li & Tingting Gong & Huiting Xu & Mengqiu Xiong & Guanghua Li & Chongge You & Zhaofan Lu, 2023. "A multiplex blood-based assay targeting DNA methylation in PBMCs enables early detection of breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    8. Del Corso, Gianna M. & Romani, Francesco, 2019. "Adaptive nonnegative matrix factorization and measure comparisons for recommender systems," Applied Mathematics and Computation, Elsevier, vol. 354(C), pages 164-179.
    9. P Fogel & C Geissler & P Cotte & G Luta, 2022. "Applying separative non-negative matrix factorization to extra-financial data," Working Papers hal-03689774, HAL.
    10. Aleix Prat & Fara Brasó-Maristany & Olga Martínez-Sáez & Esther Sanfeliu & Youli Xia & Meritxell Bellet & Patricia Galván & Débora Martínez & Tomás Pascual & Mercedes Marín-Aguilera & Anna Rodríguez &, 2023. "Circulating tumor DNA reveals complex biological features with clinical relevance in metastatic breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    11. Xiao-Bai Li & Jialun Qin, 2017. "Anonymizing and Sharing Medical Text Records," Information Systems Research, INFORMS, vol. 28(2), pages 332-352, June.
    12. Maria Pouyiourou & Bianca N. Kraft & Timothy Wohlfromm & Michael Stahl & Boris Kubuschok & Harald Löffler & Ulrich T. Hacker & Gerdt Hübner & Lena Weiss & Michael Bitzer & Thomas Ernst & Philipp Schüt, 2023. "Nivolumab and ipilimumab in recurrent or refractory cancer of unknown primary: a phase II trial," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    13. Jakob Hartmann & Thomas Bajaj & Joy Otten & Claudia Klengel & Tim Ebert & Anne-Kathrin Gellner & Ellen Junglas & Kathrin Hafner & Elmira A. Anderzhanova & Fiona Tang & Galen Missig & Lindsay Rexrode &, 2024. "SKA2 regulated hyperactive secretory autophagy drives neuroinflammation-induced neurodegeneration," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    14. Naiyang Guan & Lei Wei & Zhigang Luo & Dacheng Tao, 2013. "Limited-Memory Fast Gradient Descent Method for Graph Regularized Nonnegative Matrix Factorization," PLOS ONE, Public Library of Science, vol. 8(10), pages 1-10, October.
    15. Spelta, A. & Pecora, N. & Rovira Kaltwasser, P., 2019. "Identifying Systemically Important Banks: A temporal approach for macroprudential policies," Journal of Policy Modeling, Elsevier, vol. 41(1), pages 197-218.
    16. M. Moghadam & K. Aminian & M. Asghari & M. Parnianpour, 2013. "How well do the muscular synergies extracted via non-negative matrix factorisation explain the variation of torque at shoulder joint?," Computer Methods in Biomechanics and Biomedical Engineering, Taylor & Francis Journals, vol. 16(3), pages 291-301.
    17. Markovsky, Ivan & Niranjan, Mahesan, 2010. "Approximate low-rank factorization with structured factors," Computational Statistics & Data Analysis, Elsevier, vol. 54(12), pages 3411-3420, December.
    18. Paul Fogel & Yann Gaston-Mathé & Douglas Hawkins & Fajwel Fogel & George Luta & S. Stanley Young, 2016. "Applications of a Novel Clustering Approach Using Non-Negative Matrix Factorization to Environmental Research in Public Health," IJERPH, MDPI, vol. 13(5), pages 1-14, May.
    19. Le Thi Khanh Hien & Duy Nhat Phan & Nicolas Gillis, 2022. "Inertial alternating direction method of multipliers for non-convex non-smooth optimization," Computational Optimization and Applications, Springer, vol. 83(1), pages 247-285, September.
    20. Chae, Bongsug (Kevin), 2018. "The Internet of Things (IoT): A Survey of Topics and Trends using Twitter Data and Topic Modeling," 22nd ITS Biennial Conference, Seoul 2018. Beyond the boundaries: Challenges for business, policy and society 190376, International Telecommunications Society (ITS).

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35320-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.