Artificial Intelligence-Driven Proteomics Identifies Plasma Protein Signatures for Diagnosis and Stratification of Behçet's Disease.

Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany)
Published Date:

Abstract

The diagnosis of Behçet's disease (BD) predominantly relies on clinical symptoms, indicating an urgent for identifying potential biomarkers for early diagnosis and disease stratification. We employed an in-depth proteomics platform based on data-independent acquisition mass spectrometry (DIA-MS) and customizable antibody microarray technology, combined with machine learning methods. By analyzing the proteomic data in the training cohort, we trained an XGBoost machine learning model, and validated the model in an independent cohort. The model displayed a favorable performance in BD diagnosis and stratification. In the training set, the area under the curve (AUC) of the diagnostic model was 0.984 with an accuracy of 0.935. In the validation set, the AUC was 0.967 with an accuracy of 0.871. The AUCs for differentiating different severity BD groups ranged from 0.897 to 0.986 in the training set, and from 0.718 to 0.960 in the validation set. Functional analysis indicated that processes such as defense response, protein activation cascade, and complement activation were related to disease severity. Complement C4B was crucial in the protein-protein interaction network. This study is the first to construct an artificial intelligence-based BD diagnosis and stratification model, providing potential biomarkers and new strategies for precise diagnosis and treatment of BD. The diagnosis of BD predominantly relies on clinical symptoms, indicating an urgent for identifying potential biomarkers for early diagnosis and disease stratification. We employed an in-depth proteomics platform based on data-independent acquisition mass spectrometry (DIA-MS) and customizable antibody microarray technology, combined with machine learning methods. By analyzing the proteomic data in the training cohort, we trained an XGBoost machine learning model, and validated the model in an independent cohort. The model displayed a favorable performance in BD diagnosis and stratification. In the training set, the area under the curve (AUC) of the diagnostic model was 0.984 with an accuracy of 0.935. In the validation set, the AUC was 0.967 with an accuracy of 0.871. The AUCs for differentiating different severity BD groups ranged from 0.897 to 0.986 in the training set, and from 0.718 to 0.960 in the validation set. Functional analysis indicated that processes such as defense response, protein activation cascade, and complement activation were related to disease severity. Complement C4B was crucial in the protein-protein interaction network. This study is the first to construct an artificial intelligence-based BD diagnosis and stratification model, providing potential biomarkers and new strategies for precise diagnosis and treatment of BD.

Authors

  • Linlin Cheng
    Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.
  • Mansheng Li
    State Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Science-Beijing (PHOENIX Center), Beijing Institute of Lifeomics, Beijing, 102206, China.
  • Zhou Bai
    National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/ National Center of Gerontology, Beijing, 100730, P. R. China.
  • Xiaobo Yu
    State Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Science-Beijing (PHOENIX Center), Beijing Institute of Lifeomics, Beijing, 102206, China.
  • Wenjie Zheng
    Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, State Key Laboratory of Complex Severe and Rare Diseases, and Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, 100730, China.
  • Yongzhe Li
    School of Nuclear Science and Technology, University of Science and Technology of China, Hefei, 230026, China.
  • Yudong Liu

Keywords

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