Deep autoencoder as an interpretable tool for Raman spectroscopy investigation of chemical and extracellular vesicle mixtures
Mohammadrahim Kazemzadeh, Miguel Martínez-Calderón, Robert Otupiri, Anastasiia Artuyants, MoiMoi Lowe, Xia Ning, Eduardo Reátegui, Zachary D. Schultz, Weiliang Xu, Cherie Blenkiron, Lawrence W. Chamley, Neil G. R. Broderick, Colin L. Hisey
Abstract
Surface-enhanced Raman spectroscopy (SERS) is a powerful tool that provides valuable insight into the molecular contents of chemical and biological samples. However, interpreting Raman spectra from complex or dynamic datasets remains challenging, particularly for highly heterogeneous biological samples like extracellular vesicles (EVs). To overcome this, we developed a tunable and interpretable deep autoencoder for the analysis of several challenging Raman spectroscopy applications, including synthetic datasets, chemical mixtures, a chemical milling reaction, and mixtures of EVs. We compared the results with classical methods (PCA and UMAP) to demonstrate the superior performance of the proposed technique. Our method can handle small datasets, provide a high degree of generalization such that it can fill unknown gaps within spectral datasets, and even quantify relative ratios of cell line-derived EVs to fetal bovine serum-derived EVs within mixtures. This simple yet robust approach will greatly improve the analysis capabilities for many other Raman spectroscopy applications.