Epigenomic modifications define chromatin states to regulate cell-free DNA fragmentomics

Area of Science:

• Genomics
• Epigenetics
• Cancer Biomarkers

Background:

• Plasma cell-free DNA (cfDNA) fragmentomics show potential as cancer biomarkers.
• The molecular mechanisms regulating cfDNA fragmentation are not fully understood.

Purpose of the Study:

• Investigate the role of epigenomic modifications in cfDNA fragmentation.
• Identify specific chromatin features associated with cfDNA fragmentation patterns.
• Develop an AI-powered model for cancer detection using cfDNA fragmentomics.

Main Methods:

• Correlating cfDNA fragmentomic features with epigenetic marks in cfDNA.
• Segmenting the genome into chromatin states using histone modification signals.
• Developing and validating the TEANA AI model for pan-cancer analysis.

Main Results:

• Strong correlations found between cfDNA fragmentomics and epigenetic marks.
• Specific chromatin states are consistently associated with cfDNA fragmentation.
• Transposon Element (TE) fragmentomic features demonstrate superior performance in cancer diagnosis compared to genome-wide metrics.
• The TEANA model achieved robust performance in pan-cancer detection and tumor-origin prediction.

Conclusions:

• Chromatin organization is a key regulator of cfDNA fragmentation.
• Dysregulated TEs in cfDNA provide highly informative biomarkers for cancer diagnosis.
• AI-driven analysis of TE fragmentomics enables effective pan-cancer detection.