Creating Chemiluminescence Signature Arrays Coupled with Machine Learning for Alzheimer's Disease Serum Diagnosis.

Journal: Research (Washington, D.C.)
Published Date: May 12, 2025

Abstract

Although omics and multi-omics approaches are the most used methods to create signature arrays for liquid biopsy, the high cost of omics technologies still largely limits their wide applications for point-of-care. Inspired by the bat echolocation mechanism, we propose an "echoes" approach for creating chemiluminescence signatures via screening of a compound library, and serum samples of Alzheimer's disease (AD) were used for our proof-of-concept study. We first demonstrated the discrepancy in physicochemical properties between AD and healthy control serums. On this basis, we developed a simple, cost-effective, and versatile platform termed UNICODE (UNiversal Interaction of Chemiluminescence echOes for Disease Evaluation). The UNICODE platform consists of a "bat" probe, which generates different chemiluminescence intensities upon interacting with various substrates, and a panel/array of "flag" molecules that are selected from library screening. The UNICODE array could enable the reflecting/"echoing" of the signatures of various serum components and intact physicochemical interactions between serum substrates. In this study, we screened a library of over 1,000 small molecules and identified 12 "flag" molecules (top 12) that optimally depict the differences between AD and healthy control serums. Finally, we employed the top 12 array to conduct tests on serum samples and utilized machine learning methods to optimize detection performance. We successfully distinguished AD serums, achieving the highest area under the curve of 90.24% with the random forest method. Our strategy could provide new insights into biofluid abnormality and prototype tools for developing liquid biopsy diagnoses for AD and other diseases.

Authors

  • Biyue Zhu
    Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA.
  • Yanbo Li
    Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
  • Shi Kuang
    Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA.
  • Huizhe Wang
    Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA.
  • Astra Yu
    Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA.
  • Jing Zhang
    MOEMIL Laboratory, School of Optoelectronic Information, University of Electronic Science and Technology of China, Chengdu, China.
  • Jun Yang
    Cardiovascular Endocrinology Laboratory, Hudson Institute of Medical Research, Clayton, Victoria, Australia; Department of Medicine, Monash University, Clayton, Victoria, Australia.
  • Johnson Wang
    Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA.
  • Shiqian Shen
    Department of Anesthesia, MGH Center for Translational Pain Research, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Xuan Zhai
    Department of Pharmacy, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
  • Jiajun Xie
    Department of Pharmacy, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
  • Chongzhao Ran
    Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129, USA.

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