Diagnostic Value in Discarded Reads: Re-evaluating Multi-Mapping cfDNA Fragmentomics and GC Bias in Early-Stage Cancer.

Multi-mapping cfDNA fragments are higher in early-stage breast cancer than matched controls (median 5.38% vs 5.19%), with cross-validated AUC 0.81.

• Why it matters: Standard low-MAPQ filtering may remove cancer-linked signal from repetitive, often hypomethylated satellite DNA, but the diagnostic value of retained multi-mapping fragments is unclear.
• What they did: In 25 stage I–III breast cancer patients and 25 matched controls (plus 8 matched HCC pairs), the fraction with MAPQ < 30 was computed and tested with leave-one-pair-out models under GC/depth controls.
• The result: The excess concentrated in centromeric/heterochromatic bands (22.0% to 23.4%; p = 0.004) and persisted after GC/depth adjustment (AUC 0.64–0.76), but the breast-trained model failed in HCC (AUC 0.73; p = 0.36).

AI summary of the abstract · may contain errors · not medical advice · read the paper.