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ORIGINAL RESEARCH article

Front. Genet.
Sec. Human and Medical Genomics
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1527884

Exploration of cfDNA landscape in NIPT and clinical utilities of cfDNA based gene expression inference in prenatal diagnostics

Provisionally accepted
Ruo Jia Ruo Jia 1Jianjiang Zhu Jianjiang Zhu 2Feng Zhang Feng Zhang 3Yangbo Sun Yangbo Sun 4Bin Zhang Bin Zhang 5Hong Qi Hong Qi 2Yang Du Yang Du 4*
  • 1 Shenyang Maternity and Child Health Hospital, Shenyang, Liaoning Province, China
  • 2 Haidian Maternal and Child Health Hospital of Beijing, Beijing, China
  • 3 Changzhou Maternal and Child Health Care Hospital, Changzhou, Jiangsu Province, China
  • 4 Annoroad Gene Technology (China), Beijing, Beijing Municipality, China
  • 5 Nanjing Medical University, Nanjing, Jiangsu Province, China

The final, formatted version of the article will be published soon.

    Cell-free DNA (cfDNA) is a dynamic biomarker reflecting the physiological state of the body. Its unique physical and biochemical properties, inherited from the tissue of origin, enable a wide range of clinical applications. From methylation patterns and fragmentation profiles to genetic variants, cfDNA holds immense potential for diagnosing and monitoring various diseases, including cancer. In this study, we leverage a large collection of noninvasive prenatal testing (NIPT) dataset to explore the genomic landscape of fetal cfDNA, aiming to identify novel biomarkers associated with fetal development and maternal-fetal complications. Our study identifies novel fetal-specific genomic regions, further demonstrating the potential of cfDNA as a versatile biomarker. The prediction model achieved a 100% (12 of 12) positive predictive value (PPV) for hypothyroidism. Whereas for preeclampsia the PPV is much lower (25%, 3 of 12). By establishing a foundation for early hypothyroidism prediction and preeclampsia, we contribute to the expanding applications of NIPT. This approach can be adapted to explore other complex phenotypes and inform biomarker discovery, ultimately advancing maternal-fetal medicine.

    Keywords: cfDNA, Chromatin, Fragmentomics, Gene Expression, Hypothyroidism, NiPt, Preeclampsia, WGS

    Received: 14 Nov 2024; Accepted: 05 Feb 2025.

    Copyright: © 2025 Jia, Zhu, Zhang, Sun, Zhang, Qi and Du. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Yang Du, Annoroad Gene Technology (China), Beijing, Beijing Municipality, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.