Affiliation:
1. Ningbo University
2. Fujian Normal University
3. Northeastern University
4. Ministry of Education
Abstract
It is now understood that genes and their various mutations are associated with the onset and progression of diseases. However, routine genetic testing techniques are limited by their high cost, time consumption, susceptibility to contamination, complex operation, and data analysis difficulties, rendering them unsuitable for genotype screening in many cases. Therefore, there is an urgent need to develop a rapid, sensitive, user-friendly, and cost-effective method for genotype screening and analysis. In this study, we propose and investigate a Raman spectroscopic method for achieving fast and label-free genotype screening. The method was validated using spontaneous Raman measurements of wild-type Cryptococcus neoformans and its six mutants. An accurate identification of different genotypes was achieved by employing a one-dimensional convolutional neural network (1D-CNN), and significant correlations between metabolic changes and genotypic variations were revealed. Genotype-specific regions of interest were also localized and visualized using a gradient-weighted class activation mapping (Grad-CAM)-based spectral interpretable analysis method. Furthermore, the contribution of each metabolite to the final genotypic decision-making was quantified. The proposed Raman spectroscopic method demonstrated huge potential for fast and label-free genotype screening and analysis of conditioned pathogens.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Liaoning Province
Natural Science Foundation of Zhejiang Province
General scientific Research Project of Zhejiang Education Department
Program for the Introduction of High-End Foreign Experts
K. C. Wong Magna Fund in Ningbo University
Subject
Atomic and Molecular Physics, and Optics,Biotechnology