EGAGenomicsN/Ahttps://ega-archive.org/datasets/EGAD000010083527EGA dataset EGAD00001008352EGAProfiling of circulating tumor DNA (ctDNA) may offer a non-invasive approach to monitor disease progression. Here, we develop a quantitative method, exploiting local tissue-specific cell-free DNA (cfDNA) degradation patterns, that accurately estimates ctDNA burden independent of genomic aberrations. Nucleosome-dependent cfDNA degradation at promoters and first exon-intron junctions is strongly associated with differential transcriptional activity in tumors and blood. A quantitative model, based on just 6 regulatory regions, could accurately predict ctDNA levels in colorectal cancer patients. Strikingly, a model restricted to blood-specific regulatory regions could predict ctDNA levels across both colorectal and breast cancer patients. Using compact targeted sequencing (<25 kb) of predictive regions, we demonstrate how the approach could enable quantitative low-cost tracking of ctDNA dynamics and disease progression.Tissue-specific cell-free DNA degradation quantifies circulating tumor DNA burden.Zhu Guanhua G, Guo Yu A YA, Ho Danliang D, Poon Polly P, Poh Zhong Wee ZW, Wong Pui Mun PM, Gan Anna A, Chang Mei Mei MM, Kleftogiannis Dimitrios D, Lau Yi Ting YT, Tay Brenda B, Lim Wan Jun WJ, Chua Clarinda C, Tan Tira J TJ, Koo Si-Lin SL, Chong Dawn Q DQ, Yap Yoon Sim YS, Tan Iain I, Ng Sarah S, Skanderup Anders J AJfalse32f542a0-6702-47f2-b7d3-25b0c268fe31 - samplesWGS data of buffy coat from CRC patients2021-12-17 10:26:01EGAD00001008352960633850132EGAC00001001733EGAS00001004657