Table 2.

Histone modifications and nucleosomal positioning in cfDNA from plasma.

Cf Nucleosome Feature	Method	Control Cohort Used for Method Establishment	Cancer Entity Tested	Result	Reference
Nucleosome positioning	Evaluation of windowed protection score (WPS) using deep WGS	Pooled (n = 1) and individual cfDNA (n = 2) from healthy controls	Small and squamous cell lung cancer, colorectal adenocarcinoma, hepatocellular carcinoma, ductal carcinoma in situ breast cancer	Matched 3 out of 5 cancer test samples to a reference cell-of-origin model	[8]
Nucleosome depleted regions	Analysis of promoter read depth using deep WGS	cfDNA from healthy controls (n = 104)	Colon (n = 128), prostate (n = 139), breast (n = 125), lung (n = 31) cancers	Identified expressed cancer driver genes from cfDNA in regions with copy number gains	[63]
Nucleosome phasing	Analysis of differential phasing of upstream and downstream cfDNA fragments using WGS	Pooled cfDNA (n = 32) from healthy controls	Hepatocellular carcinoma (n = 90), colorectal (n = 11), and lung (n = 9) cancers	Positive correlation of nucleosome phasing between cell-of-origin and patient cfDNA	[71]
Nucleosome footprinting	Assessment of transcription factor accessibility score using WGS	cfDNA from healthy controls (n = 24)	Prostate (n = 8), breast (n = 2), colon (n = 1) cancers	Identified cell lineage reprogramming in prostate cancer; identified increased accessibility by tumor entity specific TFs in breast and colon cancer samples	[72]
Histone modifications	cfDNA ChIP-seq	cfDNA from healthy controls (n = 61)	Metastatic colorectal cancer (n = 56)	Colorectal cancer classifier was established based on histone modification occupancy-inferred expression; longitudinal monitoring reflected the clinical status of patients	[29]
Histone modifications	cfDNA ChIP-qPCR	n/a	Non-small cell lung cancer (n = 14)	Correlation of H3K36me3 occupancy and gene expression in lung cancer associated genes	[74]

WGS: whole genome sequencing.