Fig. 1.

Schematic of distinct types of cfDNA cleavage analysis for cfDNA molecules. The terminal 4 nucleotides at each of the 5′ fragment ends (i.e., 4-mer end motifs; n = 256) were determined from 93 murine cfDNA samples, including WT mice and nuclease-deficient mice. Six categories of distinct types of cfDNA cleavage patterns were found, referred to as "founder" end-motif profiles (i.e., F-profiles), by applying NMF analysis to the 4-mer end-motif profiles. F-profiles I, II, and III were associated with the cutting preference of DNASE1L3, DNASE1, and DFFB, respectively. The distinct types of cfDNA cleavage patterns learned from murine cfDNA could be extrapolated to human cfDNA for informing the proportional contributions of F-profiles in both mouse and human cfDNA samples (referred to as deconvolutional analysis of end motifs), allowing the detection of immune diseases and cancers.