Multimodal analysis of cell-free DNA whole-methylome sequencing for cancer detection and localization
Abstract Multimodal epigenetic characterization of cell-free DNA (cfDNA) could improve the performance of blood-based early cancer detection. However, integrative profiling of cfDNA methylome and fragmentome has been technologically challenging. Here, we adapt an enzyme-mediated methylation sequenci...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-09-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-41774-w |
| _version_ | 1827709797222318080 |
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| author | Fenglong Bie Zhijie Wang Yulong Li Wei Guo Yuanyuan Hong Tiancheng Han Fang Lv Shunli Yang Suxing Li Xi Li Peiyao Nie Shun Xu Ruochuan Zang Moyan Zhang Peng Song Feiyue Feng Jianchun Duan Guangyu Bai Yuan Li Qilin Huai Bolun Zhou Yu S. Huang Weizhi Chen Fengwei Tan Shugeng Gao |
| author_facet | Fenglong Bie Zhijie Wang Yulong Li Wei Guo Yuanyuan Hong Tiancheng Han Fang Lv Shunli Yang Suxing Li Xi Li Peiyao Nie Shun Xu Ruochuan Zang Moyan Zhang Peng Song Feiyue Feng Jianchun Duan Guangyu Bai Yuan Li Qilin Huai Bolun Zhou Yu S. Huang Weizhi Chen Fengwei Tan Shugeng Gao |
| author_sort | Fenglong Bie |
| collection | DOAJ |
| description | Abstract Multimodal epigenetic characterization of cell-free DNA (cfDNA) could improve the performance of blood-based early cancer detection. However, integrative profiling of cfDNA methylome and fragmentome has been technologically challenging. Here, we adapt an enzyme-mediated methylation sequencing method for comprehensive analysis of genome-wide cfDNA methylation, fragmentation, and copy number alteration (CNA) characteristics for enhanced cancer detection. We apply this method to plasma samples of 497 healthy controls and 780 patients of seven cancer types and develop an ensemble classifier by incorporating methylation, fragmentation, and CNA features. In the test cohort, our approach achieves an area under the curve value of 0.966 for overall cancer detection. Detection sensitivity for early-stage patients achieves 73% at 99% specificity. Finally, we demonstrate the feasibility to accurately localize the origin of cancer signals with combined methylation and fragmentation profiling of tissue-specific accessible chromatin regions. Overall, this proof-of-concept study provides a technical platform to utilize multimodal cfDNA features for improved cancer detection. |
| first_indexed | 2024-03-10T17:27:10Z |
| format | Article |
| id | doaj.art-1dac2947a89c4d6f857ab60c3f8e4c7c |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:27:10Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-1dac2947a89c4d6f857ab60c3f8e4c7c2023-11-20T10:07:16ZengNature PortfolioNature Communications2041-17232023-09-0114111310.1038/s41467-023-41774-wMultimodal analysis of cell-free DNA whole-methylome sequencing for cancer detection and localizationFenglong Bie0Zhijie Wang1Yulong Li2Wei Guo3Yuanyuan Hong4Tiancheng Han5Fang Lv6Shunli Yang7Suxing Li8Xi Li9Peiyao Nie10Shun Xu11Ruochuan Zang12Moyan Zhang13Peng Song14Feiyue Feng15Jianchun Duan16Guangyu Bai17Yuan Li18Qilin Huai19Bolun Zhou20Yu S. Huang21Weizhi Chen22Fengwei Tan23Shugeng Gao24Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeGenecast Biotechnology Co., Ltd.Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeGenecast Biotechnology Co., Ltd.Genecast Biotechnology Co., Ltd.Genecast Biotechnology Co., Ltd.Genecast Biotechnology Co., Ltd.Genecast Biotechnology Co., Ltd.Genecast Biotechnology Co., Ltd.Genecast Biotechnology Co., Ltd.Department of Thoracic Surgery, The First Hospital of China Medical UniversityDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeGenecast Biotechnology Co., Ltd.Genecast Biotechnology Co., Ltd.Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract Multimodal epigenetic characterization of cell-free DNA (cfDNA) could improve the performance of blood-based early cancer detection. However, integrative profiling of cfDNA methylome and fragmentome has been technologically challenging. Here, we adapt an enzyme-mediated methylation sequencing method for comprehensive analysis of genome-wide cfDNA methylation, fragmentation, and copy number alteration (CNA) characteristics for enhanced cancer detection. We apply this method to plasma samples of 497 healthy controls and 780 patients of seven cancer types and develop an ensemble classifier by incorporating methylation, fragmentation, and CNA features. In the test cohort, our approach achieves an area under the curve value of 0.966 for overall cancer detection. Detection sensitivity for early-stage patients achieves 73% at 99% specificity. Finally, we demonstrate the feasibility to accurately localize the origin of cancer signals with combined methylation and fragmentation profiling of tissue-specific accessible chromatin regions. Overall, this proof-of-concept study provides a technical platform to utilize multimodal cfDNA features for improved cancer detection.https://doi.org/10.1038/s41467-023-41774-w |
| spellingShingle | Fenglong Bie Zhijie Wang Yulong Li Wei Guo Yuanyuan Hong Tiancheng Han Fang Lv Shunli Yang Suxing Li Xi Li Peiyao Nie Shun Xu Ruochuan Zang Moyan Zhang Peng Song Feiyue Feng Jianchun Duan Guangyu Bai Yuan Li Qilin Huai Bolun Zhou Yu S. Huang Weizhi Chen Fengwei Tan Shugeng Gao Multimodal analysis of cell-free DNA whole-methylome sequencing for cancer detection and localization Nature Communications |
| title | Multimodal analysis of cell-free DNA whole-methylome sequencing for cancer detection and localization |
| title_full | Multimodal analysis of cell-free DNA whole-methylome sequencing for cancer detection and localization |
| title_fullStr | Multimodal analysis of cell-free DNA whole-methylome sequencing for cancer detection and localization |
| title_full_unstemmed | Multimodal analysis of cell-free DNA whole-methylome sequencing for cancer detection and localization |
| title_short | Multimodal analysis of cell-free DNA whole-methylome sequencing for cancer detection and localization |
| title_sort | multimodal analysis of cell free dna whole methylome sequencing for cancer detection and localization |
| url | https://doi.org/10.1038/s41467-023-41774-w |
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