Current machine learning-based methods have achieved inspiring predictions in the scenarios of mono-type and multi-type drug-drug interactions (DDIs), but they all ignore enhancive and depressive pharmacological changes triggered by DDIs. In addition, these pharmacological changes are asymmetric since the roles of two drugs in an interaction are different. More importantly, these pharmacological changes imply significant topological patterns among DDIs. To address the above issues, we first leverage Balance theory and Status theory in social networks to reveal the topological patterns among directed pharmacological DDIs, which are modeled as a signed and directed network. Then, we design a novel graph representation learning model named SGRL-DDI (social theory-enhanced graph representation learning for DDI) to realize the multitask prediction of DDIs. SGRL-DDI model can capture the task-joint information by integrating relation graph convolutional networks with Balance and Status patterns. Moreover, we utilize task-specific deep neural networks to perform two tasks, including the prediction of enhancive/depressive DDIs and the prediction of directed DDIs. Based on DDI entries collected from DrugBank, the superiority of our model is demonstrated by the comparison with other state-of-the-art methods. Furthermore, the ablation study verifies that Balance and Status patterns help characterize directed pharmacological DDIs, and that the joint of two tasks provides better DDI representations than individual tasks. Last, we demonstrate the practical effectiveness of our model by a version-dependent test, where 88.47 and 81.38% DDI out of newly added entries provided by the latest release of DrugBank are validated in two predicting tasks respectively.

Predicting drug synergy is critical to tailoring feasible drug combination treatment regimens for cancer patients. However, most of the existing computational methods only focus on data-rich cell lines, and hardly work on data-poor cell lines. To this end, here we proposed a novel few-shot drug synergy prediction method (called HyperSynergy) for data-poor cell lines by designing a prior-guided Hypernetwork architecture, in which the meta-generative network based on the task embedding of each cell line generates cell line dependent parameters for the drug synergy prediction network. In HyperSynergy model, we designed a deep Bayesian variational inference model to infer the prior distribution over the task embedding to quickly update the task embedding with a few labeled drug synergy samples, and presented a three-stage learning strategy to train HyperSynergy for quickly updating the prior distribution by a few labeled drug synergy samples of each data-poor cell line. Moreover, we proved theoretically that HyperSynergy aims to maximize the lower bound of log-likelihood of the marginal distribution over each data-poor cell line. The experimental results show that our HyperSynergy outperforms other state-of-the-art methods not only on data-poor cell lines with a few samples (e.g., 10, 5, 0), but also on data-rich cell lines.