Development of machine learning models for the prediction of the skin sensitization potential of cosmetic compounds.

Abstract

Background: To enhance the accuracy of allergen detection in cosmetic compounds, we developed a co-culture system that combines HaCaT keratinocytes (transfected with a luciferase plasmid driven by the AKR1C2 promoter) and THP-1 cells for machine learning applications.

Methods: Following chemical exposure, cell cytotoxicity was assessed using CCK-8 to determine appropriate stimulation concentrations. RNA-Seq was subsequently employed to analyze THP-1 cells, followed by differential expression gene (DEG) analysis and weighted gene co-expression net-work analysis (WGCNA). Using two data preprocessing methods and three feature extraction techniques, we constructed and validated models with eight machine learning algorithms.

Results: Our results demonstrated the effectiveness of this integrated approach. The best performing models were random forest (RF) and voom-based diagonal quadratic discriminant analysis (voomDQDA), both achieving 100% accuracy. Support vector machine (SVM) and voom based nearest shrunken centroids (voomNSC) showed excellent performance with 96.7% test accuracy, followed by voom-based diagonal linear discriminant analysis (voomDLDA) at 95.2%. Nearest shrunken centroids (NSC), Poisson linear discriminant analysis (PLDA) and negative binomial linear discriminant analysis (NBLDA) achieved 90.5% and 90.2% accuracy, respectively. K-nearest neighbors (KNN) showed the lowest accuracy at 85.7%.

Conclusion: This study highlights the potential of integrating co-culture systems, RNA-Seq, and machine learning to develop more accurate and comprehensive in vitro methods for skin sensitization testing. Our findings contribute to the advancement of cosmetic safety assessments, potentially reducing the reliance on animal testing.