Nature Communications (Mar 2024)

Forward-predictive SERS-based chemical taxonomy for untargeted structural elucidation of epimeric cerebrosides

  • Emily Xi Tan,
  • Shi Xuan Leong,
  • Wei An Liew,
  • In Yee Phang,
  • Jie Ying Ng,
  • Nguan Soon Tan,
  • Yie Hou Lee,
  • Xing Yi Ling

DOI
https://doi.org/10.1038/s41467-024-46838-z
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 14

Abstract

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Abstract Achieving untargeted chemical identification, isomeric differentiation, and quantification is critical to most scientific and technological problems but remains challenging. Here, we demonstrate an integrated SERS-based chemical taxonomy machine learning framework for untargeted structural elucidation of 11 epimeric cerebrosides, attaining >90% accuracy and robust single epimer and multiplex quantification with <10% errors. First, we utilize 4-mercaptophenylboronic acid to selectively capture the epimers at molecular sites of isomerism to form epimer-specific SERS fingerprints. Corroborating with in-silico experiments, we establish five spectral features, each corresponding to a structural characteristic: (1) presence/absence of epimers, (2) monosaccharide/cerebroside, (3) saturated/unsaturated cerebroside, (4) glucosyl/galactosyl, and (5) GlcCer or GalCer’s carbon chain lengths. Leveraging these insights, we create a fully generalizable framework to identify and quantify cerebrosides at concentrations between 10−4 to 10−10 M and achieve multiplex quantification of binary mixtures containing biomarkers GlcCer24:1, and GalCer24:1 using their untrained spectra in the models.