Non-random fragmentation patterns in circulating cell-free DNA reflect epigenetic regulation

Area of Science:

• Genomics
• Epigenetics
• Molecular Biology

Background:

• Cell-free circulating DNA (cfDNA) in plasma, or liquid biopsy, aids in non-invasive monitoring of diseases.
• cfDNA fragmentation patterns may reflect gene regulation and chromatin features in the tissue of origin.

Purpose of the Study:

• Investigate the association between human tissue epigenetic landscapes and cfDNA patterns in plasma.
• Determine if cfDNA fragmentation patterns can indicate gene expression levels and regulation.

Main Methods:

• Deep sequencing of human cfDNA samples.
• Mapping transcription start sites within cfDNA fragments.
• Analyzing sequencing coverage near transcription start sites for gene expression patterns.

Main Results:

• cfDNA fragmentation patterns in plasma are consistent with cell line-derived patterns.
• A developed measure of gene regulation differentiated actively expressed and silenced genes based on cfDNA sequencing coverage.
• Genomic coordinates of cfDNA fragments associated with gene expression strength and patterns.

Conclusions:

• cfDNA fragmentation patterns retain characteristics of genome-wide chromatin structure analysis.
• Analysis of cfDNA fragmentation patterns can advance the development of cfDNA-based biomarkers for human conditions.