Accurate Diagnosis of Respiratory Viruses Using an Explainable Machine Learning with Mid-Infrared Biomolecular Fingerprinting of Nasopharyngeal Secretions

Accurate identification of respiratory viruses (RVs) is critical for outbreak control and public health. This study presents a diagnostic system that combines Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) from nasopharyngeal secretions with an explainable Rotary Position Embedding-Sparse Attention Transformer (RoPE-SAT) model to accurately identify multiple RVs within 10 minutes. Spectral data (4000-00 cm-1) were collected, and the bio-fingerprint region (1800-900 cm-1) was employed for analysis. Standard normal variate (SNV) normalization and second-order derivation were applied to reduce scattering and baseline drift. Gradient-weighted class activation mapping (Grad-CAM) was employed to generate saliency maps, highlighting spectral regions most relevant to classification and enhancing the interpretability of model outputs. Two independent cohorts from Beijing Youan Hospital, processed with different viral transport media (VTMs) and drying methods, were evaluated, with one including influenza B, SARS-CoV-2, and healthy controls, and the other including mycoplasma, SARS-CoV-2, and healthy controls. The model achieved sensitivity and specificity above 94.40% across both cohorts. By correlating model-selected infrared regions with known biomolecular signatures, we verified that the system effectively recognizes virus-specific spectral fingerprints, including lipids, Amide I, Amide II, Amide III, nucleic acids, and carbohydrates, and leverages their weighted contributions for accurate classification.

On-Site Precise Screening of SARS-CoV-2 Systems Using a Channel-Wise Attention-Based PLS-1D-CNN Model with Limited Infrared Signatures

During the early stages of respiratory virus outbreaks, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the efficient utilize of limited nasopharyngeal swabs for rapid and accurate screening is crucial for public health. In this study, we present a methodology that integrates attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) with the adaptive iteratively reweighted penalized least squares (airPLS) preprocessing algorithm and a channel-wise attention-based partial least squares one-dimensional convolutional neural network (PLS-1D-CNN) model, enabling accurate screening of infected individuals within 10 minutes. Two cohorts of nasopharyngeal swab samples, comprising 126 and 112 samples from suspected SARS-CoV-2 Omicron variant cases, were collected at Beijing You'an Hospital for verification. Given that ATR-FTIR spectra are highly sensitive to variations in experimental conditions, which can affect their quality, we propose a biomolecular importance (BMI) evaluation method to assess signal quality across different conditions, validated by comparing BMI with PLS-GBM and PLS-RF results. For the ATR-FTIR signals in cohort 2, which exhibited a higher BMI, airPLS was utilized for signal preprocessing, followed by the application of the channel-wise attention-based PLS-1D-CNN model for screening. The experimental results demonstrate that our model outperforms recently reported methods in the field of respiratory virus spectrum detection, achieving a recognition screening accuracy of 96.48%, a sensitivity of 96.24%, a specificity of 97.14%, an F1-score of 96.12%, and an AUC of 0.99. It meets the World Health Organization (WHO) recommended criteria for an acceptable product: sensitivity of 95.00% or greater and specificity of 97.00% or greater for testing prior SARS-CoV-2 infection in moderate to high volume scenarios.