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Fig. 4 | Genome Medicine

Fig. 4

From: cfNOMe — A single assay for comprehensive epigenetic analyses of cell-free DNA

Fig. 4

Fragmentation analyses of enzymatically converted cfDNA. Nucleosome occupancy is inferred by calculating, centered on each genomic position, the number of reads with endpoints inside a window of n bases and subtracting the number of reads completely spanning this window [1]. The resulting metric is called the windowed protection score (WPSn). For cfDNA libraries with a fragment length peak at ~ 170 bp, as here, a 120-bp window has been previously used (WPS120) [1]. a The cfDNA fragmentation shows highly organized nucleosome occupancy in an alpha satellite on chromosome 8 (hg19: chr8:43,546,000–43,548,000). Black line: WPS120, gray bars: fragment endpoints. b Averaged and normalized WPS120 around the TSS of 15,368 genes with positive expression in whole blood. A strong positional pattern within 1 kb of the TSS is visible in blood-derived cfDNA. All fragments are studied. c Averaged and normalized WPS120 around the TSS of the same 15,368 genes in urine-derived cfDNA. An elongated, “degraded” positional signal within 500 bp of the TSS is visible. All fragments are studied. d Quantified nucleosome positioning signal strength around the TSS ranked by gene expression in six healthy controls. Blood-derived cfDNA fragments 140–200 bp in length are studied. The nucleosome positioning signal strength at the TSS is averaged for bins containing 1000 genes in order of descending whole blood expression levels. Shown are 15,368 autosomal genes with non-zero expression in GTEx. The nucleosome positioning signal strength was also calculated for 2447 genes with zero whole blood expression and 1000 random genomic loci, for which it equals close to zero (see the “Methods” section for additional detail). ac Merged K16 datasets are analyzed. d All merged control datasets are analyzed. Black dashes represent the average of six healthy controls, error bars represent SEM. NPS nucleosome positioning signal

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