bims-fragic 2025-10-12 papers

Issue of 2025–10–12
two papers selected by
Laura Mannarino, Humanitas Research

Front Med (Lausanne). 2025 ;12 1539651

Multidimensional roles of cfDNA fragmentomics in preeclampsia: from placental hypoxia and TLR9 inflammation to clinical risk stratification.

Ziyi Guo, Bin Zhang, Di Yang, Li Wang.

Cell-free DNA (cfDNA) has emerged as a pivotal biomarker for predicting preeclampsia (PE), a multisystem syndrome characterized by placental hypoperfusion and systemic inflammation. This review synthesizes critical advances in the field, highlighting quantitative alterations in cfDNA, fragmentomic profiles, and placenta-specific methylation patterns (e.g., RASSF1A) that demonstrate significant value for early prediction and severity stratification of PE. Mechanistically, placental hypoxia-induced trophoblast apoptosis (releasing cfDNA), epigenetic dysregulation activating TLR9/NF-κB inflammatory pathways, and oxidative stress-mediated mitochondrial cfDNA fragmentation collectively drive disease progression. In clinical translation, integrating cfDNA with complementary biomarkers enhances predictive performance, though limitations persist regarding preanalytical variability and dynamic gestational changes. Future efforts must advance fragmentomics-integrated multi-omics frameworks for precision prediction, where assay standardization constitutes the fundamental translational bottleneck.

Keywords: cell-free DNA; fragmentomics; methylation; placenta; preeclampsia

DOI: https://doi.org/10.3389/fmed.2025.1539651

Analyst. 2025 Oct 07.

Breaking the double-stranded limitation: single-stranded cfDNA sequencing technology opens a new era in precision medicine.

Ziyi Zhao, Dehui Zhu, Zuoran Hou, Ying Zhou, Min Pan, Qinyu Ge.

Cell-free DNA (cfDNA) in human blood or bodily fluids has become a research and clinical focus since its discovery. The broad application of cfDNA relies on accurate and comprehensive characterization of its biological features. Currently, next-generation sequencing (NGS) remains the primary method for detecting and analyzing cfDNA, with the common library preparation strategy targeting double-stranded cfDNA fragments. Based on this strategy, researchers have identified a characteristic peak of 166 bp in cfDNA. However, short DNA, single-stranded DNA, and other irregular DNA structures and sequence information in cfDNA are often lost with such library preparation methods. The emergence of single-stranded cfDNA sequencing library preparation methods effectively addresses these limitations, enabling systematic characterization of cfDNA's structural and sequence features, thereby providing more accurate non-invasive diagnostic materials for clinical applications. This review systematically summarizes single-stranded cfDNA library preparation techniques and the clinical applications of plasma cfDNA, laying the foundation for its broader utilization.

DOI: https://doi.org/10.1039/d5an00632e