A novel approach to generate robust classification models to predict developmental toxicity from imbalanced datasets

Abstract

Computational models to predict the developmental toxicity of compounds are built on imbalanced datasets wherein the toxicants outnumber the non-toxicants. Consequently, the results are biased towards the majority class (toxicants). To overcome this problem and to obtain sensitive but also accurate classifiers, we followed an integrated approach wherein (i) Synthetic Minority Over Sampling (SMOTE) is used for re-sampling, (ii) genetic algorithm (GA) is used for variable selection and (iii) support vector machines (SVM) is used for model development. The best model, M3, has (i) sensitivity (SE) = 85.54% and specificity (SP) = 85.62% in leave-one-out validation, (ii) classification accuracy of the training set = 99.67%, (iii) classification accuracy of the test set = 92.59%; and (iv) sensitivity = 92.68, specificity = 92.31 on the test set. Consensus prediction based on models M3–M5 improved these percentages by 5% over M3. From the analysis of results we infer that data imbalance in toxicity studies can be effectively addressed by the application of re-sampling techniques.

Keywords:

• QSAR
• SMOTE
• GA
• SVM
• developmental toxicity