Abstract

The fragmentation patterns of cell-free DNA (cfDNA) in plasma can potentially be utilized as diagnostic biomarkers in liquid biopsy. However, our knowledge of this biological process and the information encoded in fragmentation patterns remains preliminary. Here, we investigated the cfDNA fragmentomic characteristics against nucleosome positioning patterns in hematopoietic cells. cfDNA molecules with ends located within nucleosomes were relatively shorter with altered end motif patterns, demonstrating the feasibility of enriching tumor-derived cfDNA in patients with cancer through the selection of molecules possessing such ends. We then developed three cfDNA fragmentomic metrics after end selection, which showed significant alterations in patients with cancer and enabled cancer diagnosis. By incorporating machine learning, we further built high-performance diagnostic models, which achieved an overall area under the curve of 0.95 and 85.1% sensitivity at 95% specificity. Hence, our investigations explored the end characteristics of cfDNA fragmentomics and their merits in building accurate and sensitive cancer diagnostic models.

Title

Cell-free DNA end characteristics enable accurate and sensitive cancer diagnosis

Authors

Jia Ju, Xin Zhao, Yunyun An, Mengqi Yang, Ziteng Zhang, Xiaoyi Liu, Dingxue Hu, Wanqiu Wang , Yuqi Pan, Zhaohua Xia, Fei Fan, Xuetong Shen, Kun Sun

Journal Information

Cell Reports Methods, Volume 4, Issue 10, 21 October 2024, 100877

DOI

https://doi.org/10.1016/j.crmeth.2024.100877

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