Most Ligand-Based Classification Benchmarks Reward Memorization Rather than Generalization

Undetected overfitting can occur when there are significant redundancies between training and validation data. We describe AVE, a new measure of training-validation redundancy for ligand-based classification problems that accounts for the similarity amongst inactive molecules as well as active. We investigated seven widely-used benchmarks for virtual screening and classification, and show that the amount of AVE bias strongly correlates with the performance of ligand-based predictive methods irrespective of the predicted property, chemical fingerprint, similarity measure, or previously-applied unbiasing techniques. Therefore, it may be that the previously-reported performance of most ligand-based methods can be explained by overfitting to benchmarks rather than good prospective accuracy

Technical note: Bias and the quantification of stability

Research on bias in machine learning algorithms has generally been concerned with the impact of bias on predictive accuracy. We believe that there are other factors that should also play a role in the evaluation of bias. One such factor is the stability of the algorithm; in other words, the repeatability of the results. If we obtain two sets of data from the same phenomenon, with the same underlying probability distribution, then we would like our learning algorithm to induce approximately the same concepts from both sets of data. This paper introduces a method for quantifying stability, based on a measure of the agreement between concepts. We also discuss the relationships among stability, predictive accuracy, and bias

Optimizing 0/1 Loss for Perceptrons by Random Coordinate Descent

The 0/1 loss is an important cost function for perceptrons. Nevertheless it cannot be easily minimized by most existing perceptron learning algorithms. In this paper, we propose a family of random coordinate descent algorithms to directly minimize the 0/1 loss for perceptrons, and prove their convergence. Our algorithms are computationally efficient, and usually achieve the lowest 0/1 loss compared with other algorithms. Such advantages make them favorable for nonseparable real-world problems. Experiments show that our algorithms are especially useful for ensemble learning, and could achieve the lowest test error for many complex data sets when coupled with AdaBoost