Fluorescence Analysis of Circulating Exosomes for Breast Cancer Diagnosis Using a Sensor Array and Deep Learning.

Journal: ACS sensors
Published Date:

Abstract

Emerging liquid biopsy methods for investigating biomarkers in bodily fluids such as blood, saliva, or urine can be used to perform noninvasive cancer detection. However, the complexity and heterogeneity of exosomes require improved methods to achieve the desired sensitivity and accuracy. Herein, we report our study on developing a breast cancer liquid biopsy system, including a fluorescence sensor array and deep learning (DL) tool AggMapNet. In particular, we used a 12-unit sensor array composed of conjugated polyelectrolytes, fluorophore-labeled peptides, and monosaccharides or glycans to collect fluorescence signals from cells and exosomes. Linear discriminant analysis (LDA) processed the fluorescence spectral data of cells and cell-derived exosomes, demonstrating successful discrimination between normal and different cancerous cells and 100% accurate classification of different BC cells. For heterogeneous plasma-derived exosome analysis, CNN-based DL tool AggMapNet was applied to transform the unordered fluorescence spectra into feature maps (Fmaps), which gave a straightforward visual demonstration of the difference between healthy donors and BC patients with 100% prediction accuracy. Our work indicates that our fluorescent sensor array and DL model can be used as a promising noninvasive method for BC diagnosis.

Authors

  • Yuyao Jin
    The State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Biology, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, P. R. China.
  • Nan Du
    Tencent Medical AI Lab, Palo Alto, CA, USA.
  • Yuanfang Huang
    The State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Biology, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, P. R. China.
  • Wanxiang Shen
    Department of Chemistry, Tsinghua University, Beijing, 100084, P. R. China.
  • Ying Tan
  • Yu Zong Chen
    Bioinformatics and Drug Discovery group, Department of Pharmacy, National University of Singapore, Singapore, 117543, Singapore.
  • Wei-Tao Dou
    Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, School of Chemistry and Molecular Engineering, Frontiers Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, 130 Meilong RD, Shanghai 200237, P. R. China.
  • Xiao-Peng He
    Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, School of Chemistry and Molecular Engineering, Frontiers Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, 130 Meilong RD, Shanghai 200237, P. R. China.
  • Zijian Yang
    Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Naihan Xu
    The State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Biology, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, P. R. China.
  • Chunyan Tan
    The State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Biology, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, P. R. China.