| Title: |
Cost-effective methylome sequencing of cell-free DNA for accurately detecting and locating cancer. |
| Authors: |
Stackpole, Mary L; 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 |
| Source: |
Nature communications; vol 13, iss 1, 5566; 2041-1723 |
| Publisher Information: |
eScholarship, University of California 2022-09-01 |
| Document Type: |
Electronic Resource |
| 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. |
| Index Terms: |
Humans; Stomach Neoplasms; Cost-Benefit Analysis; Early Detection of Cancer; Cell-Free Nucleic Acids; Epigenome; Cancer; Lung Cancer; Human Genome; Colo-Rectal Cancer; Digestive Diseases; Lung; Genetics; Clinical Research; Detection; screening and diagnosis; 4.1 Discovery and preclinical testing of markers and technologies; article |
| URL: |
https://escholarship.org/uc/item/5fz8z2sx; https://escholarship.org/ |
| Availability: |
Open access content. Open access content; public |
| Note: |
application/pdf; Nature communications vol 13, iss 1, 5566 2041-1723 |
| Other Numbers: |
CDLER oai:escholarship.org:ark:/13030/qt5fz8z2sx; qt5fz8z2sx; https://escholarship.org/uc/item/5fz8z2sx; https://escholarship.org/; 1377982452 |
| Contributing Source: |
UC MASS DIGITIZATION; From OAIster®, provided by the OCLC Cooperative. |
| Accession Number: |
edsoai.on1377982452 |
| Database: |
OAIster |