Comparing the performance of meta-classifiers—a case study on selected imbalanced data sets relevant for prediction of liver toxicity

ABSTRACT: Cheminformatics datasets used in classification problems, especially those related to biological or physicochemical properties, are often imbalanced. This presents a major challenge in development of in silico prediction models, as the traditional machine learning algorithms are known to work best on balanced datasets. The class imbalance introduces a bias in the performance of these algorithms due to their preference towards the majority class. Here, we present a comparison of the performance of seven different meta-classifiers for their ability to handle imbalanced datasets, whereby Random Forest is used as base-classifier. Four different datasets that are directly (cholestasis) or indirectly (via inhibition of organic anion transporting polypeptide 1B1 and 1B3) related to liver toxicity were chosen for this purpose. The imbalance ratio in these datasets ranges between 4:1 and 20:1 for negative and positive classes, respectively. Three different sets of molecular descriptors for model development were used, and their performance was assessed in 10-fold cross-validation and on an independent validation set. Stratified bagging, MetaCost and CostSensitiveClassifier were found to be the best performing among all the methods. While MetaCost and CostSensitiveClassifier provided better sensitivity values, Stratified Bagging resulted in high balanced accuracies. GRAPHICAL ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10822-018-0116-z) contains supplementary material, which is available to authorized users.