Comparative Analysis of Recurrent Neural Networks with Conjoint Fingerprints for Skin Corrosion Prediction.

Abstract

Skin corrosion assessment is an essential toxicity end point that addresses safety concerns for topical dosage forms and cosmetic products. Previously, skin corrosion assessments required animal testing; however, differences in skin architecture and ethical concerns regarding animal models have fostered the advancement of alternative methods such as in silico and in vitro models. This study aimed to develop deep learning (DL) models based on recurrent neural networks (RNNs) for classifying skin corrosion of chemical compounds based on chemical language notation, molecular substructure, physicochemical properties, and a combination of these three properties called conjoint fingerprints. Simple RNN, long short-term memory, bidirectional long short-term memory (BiLSTM), gated recurrent units, and bidirectional gated recurrent units models, along with 11 molecular features, were employed to generate 55 RNN-based models. Applicability domain and permutation importance analysis were exploited for additional trustable prediction and explanation ability of the models, respectively. Our findings indicate that BiLSTM with conjoint features of MACCS keys and physicochemical descriptors is the most effective model with 84.3% accuracy, 89.8% area under the curve, and 57.6% Matthews correlation coefficient for the external test performance. Furthermore, our model accurately predicted the skin corrosion toxicity of all new and unseen compounds beyond our test set, highlighting prominent classification performance compared to existing skin corrosion models. This finding will contribute to the utilization of DL and conjoint characteristics of molecular structure to enhance the model's predictive capability for skin toxicity assessment.