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The diagnostic potential of proteomics and machine learning in Lyme neuroborreliosis

Author

Listed:
  • Annelaura Bach Nielsen

    (Copenhagen University Hospital - Bispebjerg and Frederiksberg Hospital
    University of Copenhagen)

  • Lasse Fjordside

    (Rigshospitalet)

  • Lylia Drici

    (University of Copenhagen)

  • Maud Eline Ottenheijm

    (Copenhagen University Hospital - Bispebjerg and Frederiksberg Hospital
    University of Copenhagen)

  • Christine Rasmussen

    (Copenhagen University Hospital - Bispebjerg and Frederiksberg Hospital)

  • Anna J. Henningsson

    (Linköping University
    Region Jönköping County)

  • Lene Holm Harritshøj

    (Copenhagen University Hospital
    University of Copenhagen)

  • Matthias Mann

    (University of Copenhagen
    Max Planck Institute of Biochemistry)

  • Helene Mens

    (Rigshospitalet)

  • Anne-Mette Lebech

    (Rigshospitalet
    University of Copenhagen)

  • Nicolai J. Wewer Albrechtsen

    (Copenhagen University Hospital - Bispebjerg and Frederiksberg Hospital
    University of Copenhagen
    Copenhagen University Hospital - Bispebjerg and Frederiksberg Hospital)

Abstract

Lyme neuroborreliosis (LNB), a nervous system infection caused by tick-borne spirochetes of the Borrelia burgdorferi sensu lato complex, is among the most frequent bacterial infections of the nervous system in Europe. Early diagnosis and continuous monitoring remain challenging due to limited sensitivity and specificity of current methods and requires invasive lumbar punctures, underscoring the need for improved, less invasive diagnostic tools. Here, we apply mass spectrometry-based proteomics to analyse 308 cerebrospinal fluid (CSF) samples and 207 plasma samples from patients with LNB, viral meningitis, controls and other manifestations of Lyme borreliosis. Diagnostic panels of regulated proteins are identified and evaluated through machine learning-assisted proteome analyses. In CSF, the classifier distinguishes LNB from viral meningitis and controls with AUCs of 0.92 and 0.90, respectively. In plasma, LNB is distinguished from controls with an AUC of 0.80. Our findings suggest a potential diagnostic role for machine learning-assisted proteomics in adults with LNB.

Suggested Citation

  • Annelaura Bach Nielsen & Lasse Fjordside & Lylia Drici & Maud Eline Ottenheijm & Christine Rasmussen & Anna J. Henningsson & Lene Holm Harritshøj & Matthias Mann & Helene Mens & Anne-Mette Lebech & Ni, 2025. "The diagnostic potential of proteomics and machine learning in Lyme neuroborreliosis," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-64903-z
    DOI: 10.1038/s41467-025-64903-z
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    References listed on IDEAS

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    1. Henry Webel & Lili Niu & Annelaura Bach Nielsen & Marie Locard-Paulet & Matthias Mann & Lars Juhl Jensen & Simon Rasmussen, 2024. "Imputation of label-free quantitative mass spectrometry-based proteomics data using self-supervised deep learning," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
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