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 nine widely-used benchmarks for virtual screening and QSAR , 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 is likely that the previously-reported performance of most ligand-based methods can be explained by overfitting to benchmarks rather than good prospective accuracy.
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.
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