Systematic biases in reference-based plasma cell-free DNA fragmentomic profiling
2024
Shenzhen Bay Laboratory, Shenzhen, China
Plasma cell-free DNA (cfDNA) fragmentation patterns are emerging directions in cancer liquid biopsy with high translational significance. Conventionally, the cfDNA sequencing reads are aligned to a reference genome to extract their fragmentomic features. In this study, through cfDNA fragmentomics profiling using different reference genomes on the same datasets in parallel, systematic biases in such conventional reference-based approaches were reported. The biases in cfDNA fragmentomic features vary among ancestries in a sample-dependent manner, and therefore might adversely affect the performances of cancer diagnosis assays across multiple clinical centres. In addition, to circumvent the analytical biases, Freefly was developed, a reference-free approach for cfDNA fragmentomics profiling. Freefly runs ∼60-fold faster than the conventional reference-based approach while generating highly consistent results. Moreover, cfDNA fragmentomic features reported by Freefly can be directly used for cancer diagnosis. Hence, Freefly possesses translational merit toward the rapid and unbiased measurement of cfDNA fragmentomics.
Systematic biases in reference-based plasma cell-free DNA fragmentomic profiling
Kun Sun
Added on: 07-08-2024
[1] https://www.cell.com/cell-reports-methods/fulltext/S2667-2375(24)00149-8
