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Early prediction of preeclampsia in pregnancy with cell-free RNA

Author

Listed:
  • Mira N. Moufarrej

    (Stanford University)

  • Sevahn K. Vorperian

    (Stanford University)

  • Ronald J. Wong

    (Stanford University School of Medicine)

  • Ana A. Campos

    (Stanford University School of Medicine)

  • Cecele C. Quaintance

    (Stanford University School of Medicine)

  • Rene V. Sit

    (Chan Zuckerberg Biohub)

  • Michelle Tan

    (Chan Zuckerberg Biohub)

  • Angela M. Detweiler

    (Chan Zuckerberg Biohub)

  • Honey Mekonen

    (Chan Zuckerberg Biohub)

  • Norma F. Neff

    (Chan Zuckerberg Biohub)

  • Courtney Baruch-Gravett

    (Global Alliance to Prevent Prematurity and Stillbirth (GAPPS))

  • James A. Litch

    (Global Alliance to Prevent Prematurity and Stillbirth (GAPPS))

  • Maurice L. Druzin

    (Stanford University School of Medicine)

  • Virginia D. Winn

    (Stanford University School of Medicine)

  • Gary M. Shaw

    (Stanford University School of Medicine)

  • David K. Stevenson

    (Stanford University School of Medicine)

  • Stephen R. Quake

    (Stanford University
    Chan Zuckerberg Biohub
    Stanford University)

Abstract

Liquid biopsies that measure circulating cell-free RNA (cfRNA) offer an opportunity to study the development of pregnancy-related complications in a non-invasive manner and to bridge gaps in clinical care1–4. Here we used 404 blood samples from 199 pregnant mothers to identify and validate cfRNA transcriptomic changes that are associated with preeclampsia, a multi-organ syndrome that is the second largest cause of maternal death globally5. We find that changes in cfRNA gene expression between normotensive and preeclamptic mothers are marked and stable early in gestation, well before the onset of symptoms. These changes are enriched for genes specific to neuromuscular, endothelial and immune cell types and tissues that reflect key aspects of preeclampsia physiology6–9, suggest new hypotheses for disease progression and correlate with maternal organ health. This enabled the identification and independent validation of a panel of 18 genes that when measured between 5 and 16 weeks of gestation can form the basis of a liquid biopsy test that would identify mothers at risk of preeclampsia long before clinical symptoms manifest themselves. Tests based on these observations could help predict and manage who is at risk for preeclampsia—an important objective for obstetric care10,11.

Suggested Citation

  • Mira N. Moufarrej & Sevahn K. Vorperian & Ronald J. Wong & Ana A. Campos & Cecele C. Quaintance & Rene V. Sit & Michelle Tan & Angela M. Detweiler & Honey Mekonen & Norma F. Neff & Courtney Baruch-Gra, 2022. "Early prediction of preeclampsia in pregnancy with cell-free RNA," Nature, Nature, vol. 602(7898), pages 689-694, February.
  • Handle: RePEc:nat:nature:v:602:y:2022:i:7898:d:10.1038_s41586-022-04410-z
    DOI: 10.1038/s41586-022-04410-z
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    Cited by:

    1. Kate E. Stanley & Tatjana Jatsenko & Stefania Tuveri & Dhanya Sudhakaran & Lore Lannoo & Kristel Calsteren & Marie Borre & Ilse Parijs & Leen Coillie & Kris Bogaert & Rodrigo Almeida Toledo & Liesbeth, 2024. "Cell type signatures in cell-free DNA fragmentation profiles reveal disease biology," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Gianluca Ursini & Pasquale Di Carlo & Sreya Mukherjee & Qiang Chen & Shizhong Han & Jiyoung Kim & Maya Deyssenroth & Carmen J. Marsit & Jia Chen & Ke Hao & Giovanna Punzi & Daniel R. Weinberger, 2023. "Prioritization of potential causative genes for schizophrenia in placenta," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. Linlin Yang & Qian Tang & Mingzhi Zhang & Yuan Tian & Xiaoxing Chen & Rui Xu & Qian Ma & Pei Guo & Chao Zhang & Da Han, 2024. "A spatially localized DNA linear classifier for cancer diagnosis," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    4. Sukanta Jash & Sayani Banerjee & Shibin Cheng & Bin Wang & Chenxi Qiu & Asami Kondo & Jan Ernerudh & Xiao Zhen Zhou & Kun Ping Lu & Surendra Sharma, 2023. "Cis P-tau is a central circulating and placental etiologic driver and therapeutic target of preeclampsia," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    5. Jun Wang & Jinyong Huang & Yunlong Hu & Qianwen Guo & Shasha Zhang & Jinglin Tian & Yanqin Niu & Ling Ji & Yuzhong Xu & Peijun Tang & Yaqin He & Yuna Wang & Shuya Zhang & Hao Yang & Kang Kang & Xinchu, 2024. "Terminal modifications independent cell-free RNA sequencing enables sensitive early cancer detection and classification," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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