Integrated fragmentomic profile and 5-Hydroxymethylcytosine of capture-based low-pass sequencing data enables pan-cancer detection via cfDNA
Background: Using epigenetic markers and fragmentomics of cell-free DNA for cancer detection has been proven applicable. Methods: We further investigated the diagnostic potential of combining two features (epigenetic markers and fragmentomic information) of cell-free DNA for detecting various types...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523323000803 |
| _version_ | 1797802856825225216 |
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| author | Zhidong Zhang Xuenan Pi Chang Gao Jun Zhang Lin Xia Xiaoqin Yan Xinlei Hu Ziyue Yan Shuxin Zhang Ailin Wei Yuer Guo Jingfeng Liu Ang Li Xiaolong Liu Wei Zhang Yanhui Liu Dan Xie |
| author_facet | Zhidong Zhang Xuenan Pi Chang Gao Jun Zhang Lin Xia Xiaoqin Yan Xinlei Hu Ziyue Yan Shuxin Zhang Ailin Wei Yuer Guo Jingfeng Liu Ang Li Xiaolong Liu Wei Zhang Yanhui Liu Dan Xie |
| author_sort | Zhidong Zhang |
| collection | DOAJ |
| description | Background: Using epigenetic markers and fragmentomics of cell-free DNA for cancer detection has been proven applicable. Methods: We further investigated the diagnostic potential of combining two features (epigenetic markers and fragmentomic information) of cell-free DNA for detecting various types of cancers. To do this, we extracted cfDNA fragmentomic features from 191 whole-genome sequencing data and studied them in 396 low-pass 5hmC sequencing data, which included four common cancer types and control samples. Results: In our analysis of 5hmC sequencing data from cancer samples, we observed aberrant ultra-long fragments (220–500 bp) that differed from normal samples in terms of both size and coverage profile. These fragments played a significant role in predicting cancer. Leveraging the ability to detect cfDNA hydroxymethylation and fragmentomic markers simultaneously in low-pass 5hmC sequencing data, we developed an integrated model that incorporated 63 features representing both fragmentomic features and hydroxymethylation signatures. This model achieved high sensitivity and specificity for pan-cancer detection (88.52% and 82.35%, respectively). Conclusion: We showed that fragmentomic information in 5hmC sequencing data is an ideal marker for cancer detection and that it shows high performance in low-pass sequencing data. |
| first_indexed | 2024-03-13T05:12:05Z |
| format | Article |
| id | doaj.art-79240cc6c7a24b5483d22edb9d4a9ad8 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-03-13T05:12:05Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-79240cc6c7a24b5483d22edb9d4a9ad82023-06-16T05:09:16ZengElsevierTranslational Oncology1936-52332023-08-0134101694Integrated fragmentomic profile and 5-Hydroxymethylcytosine of capture-based low-pass sequencing data enables pan-cancer detection via cfDNAZhidong Zhang0Xuenan Pi1Chang Gao2Jun Zhang3Lin Xia4Xiaoqin Yan5Xinlei Hu6Ziyue Yan7Shuxin Zhang8Ailin Wei9Yuer Guo10Jingfeng Liu11Ang Li12Xiaolong Liu13Wei Zhang14Yanhui Liu15Dan Xie16Laboratory of Omics Technology and Bioinformatics, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu 610041, Sichuan Province, P. R. ChinaLaboratory of Omics Technology and Bioinformatics, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu 610041, Sichuan Province, P. R. ChinaLaboratory of Omics Technology and Bioinformatics, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu 610041, Sichuan Province, P. R. ChinaTailai Inc., Shanghai 200233, P. R. ChinaLaboratory of Omics Technology and Bioinformatics, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu 610041, Sichuan Province, P. R. ChinaTailai Inc., Shanghai 200233, P. R. ChinaLaboratory of Omics Technology and Bioinformatics, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu 610041, Sichuan Province, P. R. ChinaTailai Inc., Shanghai 200233, P. R. ChinaDepartment of Neurosurgery, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu 610041, Sichuan Province, P. R. ChinaGuang'an People's Hospital, Guang'an, ChinaLaboratory of Omics Technology and Bioinformatics, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu 610041, Sichuan Province, P. R. ChinaMengchao Hepatobiliary Hospital of Fujian Medical University, Xihong Road 312, Fuzhou 350025, Fujian Province, P. R. ChinaDepartment of Pancreatic Surgery, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu 610041, Sichuan Province, P. R. ChinaMengchao Hepatobiliary Hospital of Fujian Medical University, Xihong Road 312, Fuzhou 350025, Fujian Province, P. R. ChinaDepartment of Respiratory and Critical Care Medicine, First Affiliated Hospital of the Second Military Medical University, Shanghai 200433, P. R. ChinaDepartment of Neurosurgery, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu 610041, Sichuan Province, P. R. ChinaLaboratory of Omics Technology and Bioinformatics, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu 610041, Sichuan Province, P. R. China; Corresponding author at: Laboratory of Omics Technology and Bioinformatics, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu 610041, Sichuan Province, P. R. China.Background: Using epigenetic markers and fragmentomics of cell-free DNA for cancer detection has been proven applicable. Methods: We further investigated the diagnostic potential of combining two features (epigenetic markers and fragmentomic information) of cell-free DNA for detecting various types of cancers. To do this, we extracted cfDNA fragmentomic features from 191 whole-genome sequencing data and studied them in 396 low-pass 5hmC sequencing data, which included four common cancer types and control samples. Results: In our analysis of 5hmC sequencing data from cancer samples, we observed aberrant ultra-long fragments (220–500 bp) that differed from normal samples in terms of both size and coverage profile. These fragments played a significant role in predicting cancer. Leveraging the ability to detect cfDNA hydroxymethylation and fragmentomic markers simultaneously in low-pass 5hmC sequencing data, we developed an integrated model that incorporated 63 features representing both fragmentomic features and hydroxymethylation signatures. This model achieved high sensitivity and specificity for pan-cancer detection (88.52% and 82.35%, respectively). Conclusion: We showed that fragmentomic information in 5hmC sequencing data is an ideal marker for cancer detection and that it shows high performance in low-pass sequencing data.http://www.sciencedirect.com/science/article/pii/S1936523323000803Liquid biopsyPlasma cell-free DNA5-Hydroxymethylcytosine sequencing |
| spellingShingle | Zhidong Zhang Xuenan Pi Chang Gao Jun Zhang Lin Xia Xiaoqin Yan Xinlei Hu Ziyue Yan Shuxin Zhang Ailin Wei Yuer Guo Jingfeng Liu Ang Li Xiaolong Liu Wei Zhang Yanhui Liu Dan Xie Integrated fragmentomic profile and 5-Hydroxymethylcytosine of capture-based low-pass sequencing data enables pan-cancer detection via cfDNA Translational Oncology Liquid biopsy Plasma cell-free DNA 5-Hydroxymethylcytosine sequencing |
| title | Integrated fragmentomic profile and 5-Hydroxymethylcytosine of capture-based low-pass sequencing data enables pan-cancer detection via cfDNA |
| title_full | Integrated fragmentomic profile and 5-Hydroxymethylcytosine of capture-based low-pass sequencing data enables pan-cancer detection via cfDNA |
| title_fullStr | Integrated fragmentomic profile and 5-Hydroxymethylcytosine of capture-based low-pass sequencing data enables pan-cancer detection via cfDNA |
| title_full_unstemmed | Integrated fragmentomic profile and 5-Hydroxymethylcytosine of capture-based low-pass sequencing data enables pan-cancer detection via cfDNA |
| title_short | Integrated fragmentomic profile and 5-Hydroxymethylcytosine of capture-based low-pass sequencing data enables pan-cancer detection via cfDNA |
| title_sort | integrated fragmentomic profile and 5 hydroxymethylcytosine of capture based low pass sequencing data enables pan cancer detection via cfdna |
| topic | Liquid biopsy Plasma cell-free DNA 5-Hydroxymethylcytosine sequencing |
| url | http://www.sciencedirect.com/science/article/pii/S1936523323000803 |
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