Terminal modifications independent cell-free RNA sequencing enables sensitive early cancer detection and classification
Abstract Cell-free RNAs (cfRNAs) offer an opportunity to detect diseases from a transcriptomic perspective, however, existing techniques have fallen short in generating a comprehensive cell-free transcriptome profile. We develop a sensitive library preparation method that is robust down to 100 µl in...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-01-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-44461-y |
| _version_ | 1797363165984456704 |
|---|---|
| author | Jun Wang Jinyong Huang Yunlong Hu Qianwen Guo Shasha Zhang Jinglin Tian Yanqin Niu Ling Ji Yuzhong Xu Peijun Tang Yaqin He Yuna Wang Shuya Zhang Hao Yang Kang Kang Xinchun Chen Xinying Li Ming Yang Deming Gou |
| author_facet | Jun Wang Jinyong Huang Yunlong Hu Qianwen Guo Shasha Zhang Jinglin Tian Yanqin Niu Ling Ji Yuzhong Xu Peijun Tang Yaqin He Yuna Wang Shuya Zhang Hao Yang Kang Kang Xinchun Chen Xinying Li Ming Yang Deming Gou |
| author_sort | Jun Wang |
| collection | DOAJ |
| description | Abstract Cell-free RNAs (cfRNAs) offer an opportunity to detect diseases from a transcriptomic perspective, however, existing techniques have fallen short in generating a comprehensive cell-free transcriptome profile. We develop a sensitive library preparation method that is robust down to 100 µl input plasma to analyze cfRNAs independent of their 5’-end modifications. We show that it outperforms adapter ligation-based method in detecting a greater number of cfRNA species. We perform transcriptome-wide characterizations in 165 lung cancer, 30 breast cancer, 37 colorectal cancer, 55 gastric cancer, 15 liver cancer, and 133 cancer-free participants and demonstrate its ability to identify transcriptomic changes occurring in early-stage tumors. We also leverage machine learning analyses on the differentially expressed cfRNA signatures and reveal their robust performance in cancer detection and classification. Our work sets the stage for in-depth study of the cfRNA repertoire and highlights the value of cfRNAs as cancer biomarkers in clinical applications. |
| first_indexed | 2024-03-08T16:16:55Z |
| format | Article |
| id | doaj.art-fd1ff641e7c94483a11ea6bc23bf2c4d |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-08T16:16:55Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-fd1ff641e7c94483a11ea6bc23bf2c4d2024-01-07T12:33:31ZengNature PortfolioNature Communications2041-17232024-01-0115111310.1038/s41467-023-44461-yTerminal modifications independent cell-free RNA sequencing enables sensitive early cancer detection and classificationJun Wang0Jinyong Huang1Yunlong Hu2Qianwen Guo3Shasha Zhang4Jinglin Tian5Yanqin Niu6Ling Ji7Yuzhong Xu8Peijun Tang9Yaqin He10Yuna Wang11Shuya Zhang12Hao Yang13Kang Kang14Xinchun Chen15Xinying Li16Ming Yang17Deming Gou18College of Life Sciences and Oceanography, Shenzhen UniversityCollege of Life Sciences and Oceanography, Shenzhen UniversityDepartment of Clinical Laboratory, Peking University Shenzhen HospitalCollege of Life Sciences and Oceanography, Shenzhen UniversityCollege of Life Sciences and Oceanography, Shenzhen UniversityCollege of Life Sciences and Oceanography, Shenzhen UniversityCollege of Life Sciences and Oceanography, Shenzhen UniversityDepartment of Clinical Laboratory, Peking University Shenzhen HospitalDepartment of Clinical Laboratory, People’s Hospital of Bao’an ShenzhenDepartment of Tuberculosis, The Fifth People’s Hospital of SuzhouSurgical Department, General Hospital of Ningxia Medical UniversitySchool of Basic Medical Sciences, Ningxia Medical UniversitySchool of Basic Medical Sciences, Ningxia Medical UniversityDepartment of Clinical Laboratory, The Second People’s Hospital of ShenzhenCollege of Medicine, Shenzhen UniversityCollege of Medicine, Shenzhen UniversityShenzhen Geneups Biotechnology Co.College of Life Sciences and Oceanography, Shenzhen UniversityCollege of Life Sciences and Oceanography, Shenzhen UniversityAbstract Cell-free RNAs (cfRNAs) offer an opportunity to detect diseases from a transcriptomic perspective, however, existing techniques have fallen short in generating a comprehensive cell-free transcriptome profile. We develop a sensitive library preparation method that is robust down to 100 µl input plasma to analyze cfRNAs independent of their 5’-end modifications. We show that it outperforms adapter ligation-based method in detecting a greater number of cfRNA species. We perform transcriptome-wide characterizations in 165 lung cancer, 30 breast cancer, 37 colorectal cancer, 55 gastric cancer, 15 liver cancer, and 133 cancer-free participants and demonstrate its ability to identify transcriptomic changes occurring in early-stage tumors. We also leverage machine learning analyses on the differentially expressed cfRNA signatures and reveal their robust performance in cancer detection and classification. Our work sets the stage for in-depth study of the cfRNA repertoire and highlights the value of cfRNAs as cancer biomarkers in clinical applications.https://doi.org/10.1038/s41467-023-44461-y |
| spellingShingle | Jun Wang Jinyong Huang Yunlong Hu Qianwen Guo Shasha Zhang Jinglin Tian Yanqin Niu Ling Ji Yuzhong Xu Peijun Tang Yaqin He Yuna Wang Shuya Zhang Hao Yang Kang Kang Xinchun Chen Xinying Li Ming Yang Deming Gou Terminal modifications independent cell-free RNA sequencing enables sensitive early cancer detection and classification Nature Communications |
| title | Terminal modifications independent cell-free RNA sequencing enables sensitive early cancer detection and classification |
| title_full | Terminal modifications independent cell-free RNA sequencing enables sensitive early cancer detection and classification |
| title_fullStr | Terminal modifications independent cell-free RNA sequencing enables sensitive early cancer detection and classification |
| title_full_unstemmed | Terminal modifications independent cell-free RNA sequencing enables sensitive early cancer detection and classification |
| title_short | Terminal modifications independent cell-free RNA sequencing enables sensitive early cancer detection and classification |
| title_sort | terminal modifications independent cell free rna sequencing enables sensitive early cancer detection and classification |
| url | https://doi.org/10.1038/s41467-023-44461-y |
| work_keys_str_mv | AT junwang terminalmodificationsindependentcellfreernasequencingenablessensitiveearlycancerdetectionandclassification AT jinyonghuang terminalmodificationsindependentcellfreernasequencingenablessensitiveearlycancerdetectionandclassification AT yunlonghu terminalmodificationsindependentcellfreernasequencingenablessensitiveearlycancerdetectionandclassification AT qianwenguo terminalmodificationsindependentcellfreernasequencingenablessensitiveearlycancerdetectionandclassification AT shashazhang terminalmodificationsindependentcellfreernasequencingenablessensitiveearlycancerdetectionandclassification AT jinglintian terminalmodificationsindependentcellfreernasequencingenablessensitiveearlycancerdetectionandclassification AT yanqinniu terminalmodificationsindependentcellfreernasequencingenablessensitiveearlycancerdetectionandclassification AT lingji terminalmodificationsindependentcellfreernasequencingenablessensitiveearlycancerdetectionandclassification AT yuzhongxu terminalmodificationsindependentcellfreernasequencingenablessensitiveearlycancerdetectionandclassification AT peijuntang terminalmodificationsindependentcellfreernasequencingenablessensitiveearlycancerdetectionandclassification AT yaqinhe terminalmodificationsindependentcellfreernasequencingenablessensitiveearlycancerdetectionandclassification AT yunawang terminalmodificationsindependentcellfreernasequencingenablessensitiveearlycancerdetectionandclassification AT shuyazhang terminalmodificationsindependentcellfreernasequencingenablessensitiveearlycancerdetectionandclassification AT haoyang terminalmodificationsindependentcellfreernasequencingenablessensitiveearlycancerdetectionandclassification AT kangkang terminalmodificationsindependentcellfreernasequencingenablessensitiveearlycancerdetectionandclassification AT xinchunchen terminalmodificationsindependentcellfreernasequencingenablessensitiveearlycancerdetectionandclassification AT xinyingli terminalmodificationsindependentcellfreernasequencingenablessensitiveearlycancerdetectionandclassification AT mingyang terminalmodificationsindependentcellfreernasequencingenablessensitiveearlycancerdetectionandclassification AT deminggou terminalmodificationsindependentcellfreernasequencingenablessensitiveearlycancerdetectionandclassification |