Machine Learning Interpretation of Optical Spectroscopy Using Peak-Sensitive Logistic Regression

Optical spectroscopy, a noninvasive molecular sensing technique, offers valuable insights into material characterization, molecule identification, and biosample analysis. Despite the informativeness of high-dimensional optical spectra, their interpretation remains a challenge. Machine learning methods have gained prominence in spectral analyses, efficiently unveiling analyte compositions. However, these methods still face challenges in interpretability, particularly in generating clear feature importance maps that highlight the spectral features specific to each class of data. These limitations arise from feature noise, model complexity, and the lack of optimization for spectroscopy. In this work, we introduce a machine learning algorithm─logistic regression with peak-sensitive elastic-net regularization (PSE-LR)─tailored for spectral analysis. PSE-LR enables classification and interpretability by producing a peak-sensitive feature importance map, achieving an F1-score of 0.93 and a feature sensitivity of 1.0. Its performance is compared with other methods, including k-nearest neighbors (KNN), elastic-net logistic regression (E-LR), support vector machine (SVM), principal component analysis followed by linear discriminant analysis (PCA-LDA), XGBoost, and neural network (NN). Applying PSE-LR to Raman and photoluminescence (PL) spectra, we detected the receptor-binding domain (RBD) of SARS-CoV-2 spike protein in ultralow concentrations, identified neuroprotective solution (NPS) in brain samples, recognized WS₂ monolayer and WSe₂/WS₂ heterobilayer, analyzed Alzheimer's disease (AD) brains, and suggested potential disease biomarkers. Our findings demonstrate PSE-LR's utility in detecting subtle spectral features and generating interpretable feature importance maps. It is beneficial for the spectral characterization of materials, molecules, and biosamples and applicable to other spectroscopic methods. This work also facilitates the development of nanodevices such as nanosensors and miniaturized spectrometers based on nanomaterials.