Fragmentation landscape of cell-free DNA revealed by deconvolutional analysis of end motifs
| العنوان: | Fragmentation landscape of cell-free DNA revealed by deconvolutional analysis of end motifs |
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| المؤلفون: | Ze Zhou, Mary-Jane L. Ma, Rebecca W. Y. Chan, W. K. Jacky Lam, Wenlei Peng, Wanxia Gai, Xi Hu, Spencer C. Ding, Lu Ji, Qing Zhou, Peter P. H. Cheung, Stephanie C. Y. Yu, Jeremy Y. C. Teoh, Cheuk-Chun Szeto, John Wong, Vincent W. S. Wong, Grace L. H. Wong, Stephen L. Chan, Edwin P. Hui, Brigette B. Y. Ma, Anthony T. C. Chan, Rossa W. K. Chiu, K. C. Allen Chan, Y. M. Dennis Lo, Peiyong Jiang |
| المصدر: | Proceedings of the National Academy of Sciences. 120 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Multidisciplinary |
| الوصف: | Cell-free DNA (cfDNA) fragmentation is nonrandom, at least partially mediated by various DNA nucleases, forming characteristic cfDNA end motifs. However, there is a paucity of tools for deciphering the relative contributions of cfDNA cleavage patterns related to underlying fragmentation factors. In this study, through non-negative matrix factorization algorithm, we used 256 5′ 4-mer end motifs to identify distinct types of cfDNA cleavage patterns, referred to as “founder” end-motif profiles (F-profiles). F-profiles were associated with different DNA nucleases based on whether such patterns were disrupted in nuclease-knockout mouse models. Contributions of individual F-profiles in a cfDNA sample could be determined by deconvolutional analysis. We analyzed 93 murine cfDNA samples of different nuclease-deficient mice and identified six types of F-profiles. F-profiles I, II, and III were linked to deoxyribonuclease 1 like 3 (DNASE1L3), deoxyribonuclease 1 (DNASE1), and DNA fragmentation factor subunit beta (DFFB), respectively. We revealed that 42.9% of plasma cfDNA molecules were attributed to DNASE1L3-mediated fragmentation, whereas 43.4% of urinary cfDNA molecules involved DNASE1-mediated fragmentation. We further demonstrated that the relative contributions of F-profiles were useful to inform pathological states, such as autoimmune disorders and cancer. Among the six F-profiles, the use of F-profile I could inform the human patients with systemic lupus erythematosus. F-profile VI could be used to detect individuals with hepatocellular carcinoma, with an area under the receiver operating characteristic curve of 0.97. F-profile VI was more prominent in patients with nasopharyngeal carcinoma undergoing chemoradiotherapy. We proposed that this profile might be related to oxidative stress. |
| تدمد: | 1091-6490 0027-8424 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::ebd9260fa464576f47f0fd91e97cfc65 https://doi.org/10.1073/pnas.2220982120 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........ebd9260fa464576f47f0fd91e97cfc65 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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