Drug molecular representations for drug response predictions: a comprehensive investigation via machine learning methods.

The integration of drug molecular representations into predictive models for Drug Response Prediction (DRP) is a standard procedure in pharmaceutical research and development. However, the comparative effectiveness of combining these representations with genetic profiles for DRP remains unclear. This study conducts a comprehensive evaluation of the efficacy of various drug molecular representations employing cutting-edge machine learning models under various experimental settings. Our findings reveal that the inclusion of molecular representations from either PubChem fingerprints or SMILES can significantly enhance the performance of DRPs when used in conjunction with deep learning models. However, the optimal choice of drug molecular representation can vary depending on the predictive model and the specific DRP task. The insights derived from our study offer useful guidance on selecting the most suitable drug molecular representations for constructing efficient predictive models for DRPs, aiding for drug repurposing, personalized medicine, and new drug discovery.