Hi-GeoMVP: a hierarchical geometry-enhanced deep learning model for drug response prediction.

motivationPersonalized cancer treatments require accurate drug response predictions. Existing deep learning methods show promise but higher accuracy is needed to serve the purpose of precision medicine. The prediction accuracy can be improved with not only topology but geometrical information of drugs.

resultsA novel deep learning methodology for drug response prediction is presented, named Hi-GeoMVP. It synthesizes hierarchical drug representation with multi-omics data, leveraging graph neural networks and variational autoencoders for detailed drug and cell line representations. Multi-task learning is employed to make better prediction, while both 2D and 3D molecular representations capture comprehensive drug information. Testing on the GDSC dataset confirms Hi-GeoMVP's enhanced performance, surpassing prior state-of-the-art methods by improving the Pearson correlation coefficient from 0.934 to 0.941 and decreasing the root mean square error from 0.969 to 0.931. In the case of blind test, Hi-GeoMVP demonstrated robustness, outperforming the best previous models with a superior Pearson correlation coefficient in the drug-blind test. These results underscore Hi-GeoMVP's capabilities in drug response prediction, implying its potential for precision medicine. AVAILABILITY AND IMPLEMENTATION: The source code is available at https://github.com/matcyr/Hi-GeoMVP.