Identification of multiple genomic alterations and prediction of neoantigens from circulating tumor cells at the single-cell level
Abstract Circulating tumor cells (CTCs) are linked to cancer progression and poor prognosis, offering valuable genetic insights into tumors. Accurate detection of genomic alterations in CTCs is essential for improving cancer diagnosis and treatment. To address this, we develop Uniform Chromosome Con...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62215-w |
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| author | Xiaochen Gao Xinyu Li Weize Xu Ming Jiao Yu Guo Jiajia Wang Weihao Wang Jiling Feng Qianqian Guo Chengchao Wu Taiyu Zhang Yuqin Yang Da Lin |
| author_facet | Xiaochen Gao Xinyu Li Weize Xu Ming Jiao Yu Guo Jiajia Wang Weihao Wang Jiling Feng Qianqian Guo Chengchao Wu Taiyu Zhang Yuqin Yang Da Lin |
| author_sort | Xiaochen Gao |
| collection | DOAJ |
| description | Abstract Circulating tumor cells (CTCs) are linked to cancer progression and poor prognosis, offering valuable genetic insights into tumors. Accurate detection of genomic alterations in CTCs is essential for improving cancer diagnosis and treatment. To address this, we develop Uniform Chromosome Conformation Capture (Uni-C), a method for profiling 3D chromatin architecture and genomic alterations at the single-cell level. Using Uni-C, we analyze CTCs from pancreatic cancer patient-derived xenograft (PDX) and spontaneous tumor mouse models. In the PDX model, integrating data from seven CTCs captures 88.7% of SNPs and INDELs, and 75.0% of structural variants present in tumor tissue. These findings indicate that variants detected in CTCs reflect tumor genomic features. Notably, we observe chromatin conformation differences between mitotic and interphase CTCs, suggesting potential markers of cell vitality. In the spontaneous tumor model, we identify driver gene mutations in CTCs and predict neoantigens, advancing early cancer detection and treatment strategies. |
| format | Article |
| id | doaj-art-758707103be6427da3d539e86f91e68d |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-758707103be6427da3d539e86f91e68d2025-08-20T03:46:20ZengNature PortfolioNature Communications2041-17232025-07-0116111510.1038/s41467-025-62215-wIdentification of multiple genomic alterations and prediction of neoantigens from circulating tumor cells at the single-cell levelXiaochen Gao0Xinyu Li1Weize Xu2Ming Jiao3Yu Guo4Jiajia Wang5Weihao Wang6Jiling Feng7Qianqian Guo8Chengchao Wu9Taiyu Zhang10Yuqin Yang11Da Lin12Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicinePrecision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineState Key Laboratory of Agricultural Microbiology, Huazhong Agricultural UniversityDepartment of Laboratory Animal Center, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Laboratory Animal Center, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicinePrecision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicinePrecision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicinePrecision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicinePrecision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineAffiliated Hospital of Guangdong Medical UniversityPrecision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Laboratory Animal Center, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicinePrecision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineAbstract Circulating tumor cells (CTCs) are linked to cancer progression and poor prognosis, offering valuable genetic insights into tumors. Accurate detection of genomic alterations in CTCs is essential for improving cancer diagnosis and treatment. To address this, we develop Uniform Chromosome Conformation Capture (Uni-C), a method for profiling 3D chromatin architecture and genomic alterations at the single-cell level. Using Uni-C, we analyze CTCs from pancreatic cancer patient-derived xenograft (PDX) and spontaneous tumor mouse models. In the PDX model, integrating data from seven CTCs captures 88.7% of SNPs and INDELs, and 75.0% of structural variants present in tumor tissue. These findings indicate that variants detected in CTCs reflect tumor genomic features. Notably, we observe chromatin conformation differences between mitotic and interphase CTCs, suggesting potential markers of cell vitality. In the spontaneous tumor model, we identify driver gene mutations in CTCs and predict neoantigens, advancing early cancer detection and treatment strategies.https://doi.org/10.1038/s41467-025-62215-w |
| spellingShingle | Xiaochen Gao Xinyu Li Weize Xu Ming Jiao Yu Guo Jiajia Wang Weihao Wang Jiling Feng Qianqian Guo Chengchao Wu Taiyu Zhang Yuqin Yang Da Lin Identification of multiple genomic alterations and prediction of neoantigens from circulating tumor cells at the single-cell level Nature Communications |
| title | Identification of multiple genomic alterations and prediction of neoantigens from circulating tumor cells at the single-cell level |
| title_full | Identification of multiple genomic alterations and prediction of neoantigens from circulating tumor cells at the single-cell level |
| title_fullStr | Identification of multiple genomic alterations and prediction of neoantigens from circulating tumor cells at the single-cell level |
| title_full_unstemmed | Identification of multiple genomic alterations and prediction of neoantigens from circulating tumor cells at the single-cell level |
| title_short | Identification of multiple genomic alterations and prediction of neoantigens from circulating tumor cells at the single-cell level |
| title_sort | identification of multiple genomic alterations and prediction of neoantigens from circulating tumor cells at the single cell level |
| url | https://doi.org/10.1038/s41467-025-62215-w |
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