Cell-Free DNA as a Biomarker in Metabolic Diseases

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: 20 October 2025 | Viewed by 257

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Guest Editor
1. Laboratory of Pharmacology, Department of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece
2. Institute of Agri-Food and Life Sciences, University Research and Innovation Centre, Hellenic Mediterranean University, 71003 Heraklion, Greece
Interests: epigenetics; DNA methylation; biomarker; classifier; liquid biopsy; metabolic disease; diabetes; AutoML
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Special Issue Information

Dear Colleagues,

Cell-free DNA (cfDNA) has emerged as a valuable biomarker for metabolic diseases, offering a non-invasive approach to monitor disease progression, tissue-specific damage, and treatment response. Circulating cfDNA in blood, urine, saliva, etc., derived mainly from dying cells, carries mutations and epigenetic motifs, among others, that reflect the molecular landscape of metabolic disorders. Recent advances in detection methods such as droplet digital PCR (ddPCR) or next-generation sequencing (NGS) in cfDNA analysis have provided new insights into its potential as a diagnostic and prognostic tool in conditions such as obesity, type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), cardiovascular diseases, and metabolic syndrome.

This Special Issue of Life, entitled “Cell-Free DNA as a Biomarker in Metabolic Diseases”, aims to present the latest research on the role of cfDNA in the diagnosis, prognosis, and monitoring of metabolic diseases, with a focus on the molecular mechanisms of disease pathogenesis and biomarker discovery. We invite original research and review articles exploring the biological function of cfDNA; the quantity and structure of cfDNA; and cfDNA (hydroxy)methylation, fragmentation patterns, and their correlation with metabolic dysfunction. We particularly encourage studies that employ novel sequencing technologies, bioinformatics approaches, and multi-omics integration in the study of cfDNA.

Through this Special Issue, we aim to advance the understanding of cfDNA biology, applications, and its translational potential in precision medicine for metabolic diseases.

Dr. Makrina Karaglani
Guest Editor

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Keywords

  • cell-free DNA (cfDNA)
  • liquid biopsy
  • metabolic diseases
  • obesity
  • type 2 diabetes
  • non-alcoholic fatty liver disease (NAFLD)
  • methylation
  • mutations

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Published Papers (1 paper)

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Review

37 pages, 8221 KiB  
Review
Epigenetic Profiling of Cell-Free DNA in Cerebrospinal Fluid: A Novel Biomarker Approach for Metabolic Brain Diseases
by Kyle Sporn, Rahul Kumar, Kiran Marla, Puja Ravi, Swapna Vaja, Phani Paladugu, Nasif Zaman and Alireza Tavakkoli
Life 2025, 15(8), 1181; https://doi.org/10.3390/life15081181 - 25 Jul 2025
Abstract
Due to their clinical heterogeneity, nonspecific symptoms, and the limitations of existing biomarkers and imaging modalities, metabolic brain diseases (MBDs), such as mitochondrial encephalopathies, lysosomal storage disorders, and glucose metabolism syndromes, pose significant diagnostic challenges. This review examines the growing potential of cell-free [...] Read more.
Due to their clinical heterogeneity, nonspecific symptoms, and the limitations of existing biomarkers and imaging modalities, metabolic brain diseases (MBDs), such as mitochondrial encephalopathies, lysosomal storage disorders, and glucose metabolism syndromes, pose significant diagnostic challenges. This review examines the growing potential of cell-free DNA (cfDNA) derived from cerebrospinal fluid (CSF) epigenetic profiling as a dynamic, cell-type-specific, minimally invasive biomarker approach for MBD diagnosis and monitoring. We review important technological platforms and their use in identifying CNS-specific DNA methylation patterns indicative of neuronal injury, neuroinflammation, and metabolic reprogramming, including cfMeDIP-seq, enzymatic methyl sequencing (EM-seq), and targeted bisulfite sequencing. By synthesizing current findings across disorders such as MELAS, Niemann–Pick disease, Gaucher disease, GLUT1 deficiency syndrome, and diabetes-associated cognitive decline, we highlight the superior diagnostic and prognostic resolution offered by CSF cfDNA methylation signatures relative to conventional CSF markers or neuroimaging. We also address technical limitations, interpretive challenges, and translational barriers to clinical implementation. Ultimately, this review explores CSF cfDNA epigenetic analysis as a liquid biopsy modality. The central objective is to assess whether epigenetic profiling of CSF-derived cfDNA can serve as a reliable and clinically actionable biomarker for improving the diagnosis and longitudinal monitoring of metabolic brain diseases. Full article
(This article belongs to the Special Issue Cell-Free DNA as a Biomarker in Metabolic Diseases)
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