Affiliation:
1. Hubei Key Laboratory of Agricultural Bioinformatics College of Informatics Huazhong Agricultural University Wuhan 430070 China
2. Health Science Center Hubei Minzu University Enshi 445000 China
3. Hubei Provincial Clinical Medical Research Center for Nephropathy Hubei Minzu University Enshi 445000 China
4. Key Laboratory of Smart Farming for Agricultural Animals Ministry of Agriculture and Rural Affairs Wuhan 430070 China
Abstract
AbstractCell‐free DNA (cfDNA) fragmentation patterns have immense potential for early cancer detection. However, the definition of fragmentation varies, ranging from the entire genome to specific genomic regions. These patterns have not been systematically compared, impeding broader research and practical implementation. Here, 1382 plasma cfDNA sequencing samples from 8 cancer types are collected. Considering that cfDNA within open chromatin regions is more susceptible to fragmentation, 10 fragmentation patterns within open chromatin regions as features and employed machine learning techniques to evaluate their performance are examined. All fragmentation patterns demonstrated discernible classification capabilities, with the end motif showing the highest diagnostic value for cross‐validation. Combining cross and independent validation results revealed that fragmentation patterns that incorporated both fragment length and coverage information exhibited robust predictive capacities. Despite their diagnostic potential, the predictive power of these fragmentation patterns is unstable. To address this limitation, an ensemble classifier via integrating all fragmentation patterns is developed, which demonstrated notable improvements in cancer detection and tissue‐of‐origin determination. Further functional bioinformatics investigations on significant feature intervals in the model revealed its impressive ability to identify critical regulatory regions involved in cancer pathogenesis.
Funder
Fundamental Research Funds for the Central Universities
National Natural Science Foundation of China
Cited by
1 articles.
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