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Detection of Cell-Free DNA in Blood Plasma Samples of Cancer Patients
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Circulating Cell-free DNA Fragmentomics Detection and Beyond.

Tianliang Liu1,2,3, Zhicheng Li2, Shifu Chen1,3

  • 1LifeX Institute, Gannan Medical University, Ganzhou, China.

Aging and Disease
|September 16, 2025
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Summary

Circulating cell-free DNA (cfDNA) fragmentomics offers new biomarker insights beyond sequence analysis. Analyzing cfDNA structural patterns reveals distinct signatures for disease and aging, enhancing diagnostic accuracy.

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Area of Science:

  • Biomarker Discovery
  • Molecular Diagnostics
  • Genomics

Background:

  • Circulating cell-free DNA (cfDNA) contains valuable genomic and epigenetic information.
  • Current cfDNA analyses (non-fragmentomics) face limitations in detecting subtle genomic alterations.
  • cfDNA fragmentation patterns are influenced by cellular processes and epigenetic factors.

Purpose of the Study:

  • To review cfDNA fragmentomics targets and mechanisms.
  • To explore the clinical utility of cfDNA fragmentomics in disease and aging.
  • To survey technologies and computational approaches for cfDNA fragmentomics.

Main Methods:

  • Literature review of cfDNA fragmentomics research.
  • Analysis of cfDNA structural features (size, end motifs, nucleosome footprints).
  • Exploration of fragmentation mechanisms and epigenetic influences.

Main Results:

  • cfDNA fragmentomics signatures differ significantly between healthy and diseased states, and across age groups.
  • Fragmentomics data can complement traditional non-fragmentomics analyses.
  • Distinct fragmentation patterns provide opportunities for enhanced diagnostic accuracy.

Conclusions:

  • cfDNA fragmentomics represents a promising avenue for biomarker development.
  • Understanding fragmentation mechanisms is key to unlocking cfDNA's full diagnostic potential.
  • Technological advancements are crucial for implementing cfDNA fragmentomics in clinical practice.