Disease-Ligand Identification Based on Flexible Neural Tree

In order to screen the disease-related compounds of a traditional Chinese medicine prescription in network pharmacology research accurately, a new virtual screening method based on flexible neural tree (FNT) model, hybrid evolutionary method and negative sample selection algorithm is proposed. A novel hybrid evolutionary algorithm based on the Grammar-guided genetic programming and salp swarm algorithm is proposed to infer the optimal FNT. According to hypertension, diabetes, and Corona Virus Disease 2019, disease-related compounds are collected from the up-to-date literatures. The unrelated compounds are chosen by negative sample selection algorithm. ECFP6, MACCS, Macrocycle, and RDKit are utilized to numerically characterize the chemical structure of each compound collected, respectively. The experiment results show that our proposed method performs better than classical classifiers [Support Vector Machine (SVM), random forest (RF), AdaBoost, decision tree (DT), Gradient Boosting Decision Tree (GBDT), KNN, logic regression (LR), and Naive Bayes (NB)], up-to-date classifier (gcForest), and deep learning method (forgeNet) in terms of AUC, ROC, TPR, FPR, Precision, Specificity, and F1. MACCS method is suitable for the maximum number of classifiers. All methods perform poorly with ECFP6 molecular descriptor.