Exploring per-base quality scores as a surrogate marker of cell-free DNA fragmentome.

Analyzing four independent batches (23 cancer samples: pancreatic and breast; 22 matched controls) sequenced in a within-lane regime and further normalized per flow-cell tile to reduce technical confounders, we demonstrate through unsupervised analysis that boundary-enriched dynamics captured in these quality scores consistently separate cancer from control samples.

Furthermore, we show that the quality-derived metric correlates with short-fragment enrichment and tumor-associated 5'-end motifs, performing comparably to established, motif-based orthogonal methods.