Distinct distributions of 5hmC in patient-derived cfDNA and tissue relevance. (A) The median and range of average counts are plotted against the relative genomic positions. The 5hmC-Seal data are enriched in gene bodies (split into 10 bins for all genes) relative to the flanking regions. (B) The 5hmC-Seal data are enriched in the B-cell–derived H3K4me1 loci compared with other tissue types (Student t test P < .001). H3K4me1 loci are obtained from the Roadmap Epigenomics Project data. (C) The top 100 highly variable (ie, most informative) 5hmC marker genes in cfDNA are highly correlated with those identified in the cfDNA-paired tissue samples from the same subject (n = 7). (D) The top 500 highly variable 5hmC marker genes in cfDNA are enriched within genes specific to blood compared with other tissues, based on the TiGER database for tissue-specific genes. TES, transcription end site; TSS, transcription start site.