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Plasma proteomic profiles predict individual future health risk

Author

Listed:
  • Jia You

    (Fudan University)

  • Yu Guo

    (Fudan University)

  • Yi Zhang

    (Fudan University)

  • Ju-Jiao Kang

    (Fudan University)

  • Lin-Bo Wang

    (Fudan University)

  • Jian-Feng Feng

    (Fudan University
    Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education
    Zhangjiang Fudan International Innovation Center
    Fudan University)

  • Wei Cheng

    (Fudan University
    Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education
    Zhejiang Normal University
    Shanghai Medical College and Zhongshan Hospital Immunotherapy Technology Transfer Center)

  • Jin-Tai Yu

    (Fudan University)

Abstract

Developing a single-domain assay to identify individuals at high risk of future events is a priority for multi-disease and mortality prevention. By training a neural network, we developed a disease/mortality-specific proteomic risk score (ProRS) based on 1461 Olink plasma proteins measured in 52,006 UK Biobank participants. This integrative score markedly stratified the risk for 45 common conditions, including infectious, hematological, endocrine, psychiatric, neurological, sensory, circulatory, respiratory, digestive, cutaneous, musculoskeletal, and genitourinary diseases, cancers, and mortality. The discriminations witnessed high accuracies achieved by ProRS for 10 endpoints (e.g., cancer, dementia, and death), with C-indexes exceeding 0.80. Notably, ProRS produced much better or equivalent predictive performance than established clinical indicators for almost all endpoints. Incorporating clinical predictors with ProRS enhanced predictive power for most endpoints, but this combination only exhibited limited improvement when compared to ProRS alone. Some proteins, e.g., GDF15, exhibited important discriminative values for various diseases. We also showed that the good discriminative performance observed could be largely translated into practical clinical utility. Taken together, proteomic profiles may serve as a replacement for complex laboratory tests or clinical measures to refine the comprehensive risk assessments of multiple diseases and mortalities simultaneously. Our models were internally validated in the UK Biobank; thus, further independent external validations are necessary to confirm our findings before application in clinical settings.

Suggested Citation

  • Jia You & Yu Guo & Yi Zhang & Ju-Jiao Kang & Lin-Bo Wang & Jian-Feng Feng & Wei Cheng & Jin-Tai Yu, 2023. "Plasma proteomic profiles predict individual future health risk," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43575-7
    DOI: 10.1038/s41467-023-43575-7
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