Drug-target affinity prediction using applicability domain based on data density

Abstract

In the pursuit of research and development of drug discovery, the computational prediction of the target affinity of a drug candidate is useful for screening compounds at an early stage and for verifying the binding potential to an unknown target. The chemogenomics-based method has attracted increased attention as it integrates information pertaining to the drug and target to predict drug-target affinity (DTA). However, the compound and target spaces are vast, and without sufficient training data, proper DTA prediction is not possible. If a DTA prediction is made in this situation, it will potentially lead to false predictions. In this study, we propose a DTA prediction method that can advise whether/when there are insufficient samples in the compound/target spaces based on the concept of the applicability domain (AD) and the data density of the training dataset. AD indicates a data region in which a machine learning model can make reliable predictions. By preclassifying the samples to be predicted by the constructed AD into those within (In-AD) and those outside the AD (Out-AD), we can determine whether a reasonable prediction can be made for these samples. The results of the evaluation experiments based on the use of three different public datasets showed that the AD constructed by the k-nearest neighbor (k-NN) method worked well, i.e., the prediction accuracy of the samples classified by the AD as Out-AD was low, while the prediction accuracy of the samples classified by the AD as In-AD was high.