Drug-drug interaction (DDI), as a possible result of drug combination treatment, could lead to adverse physiological reactions and increasing mortality rates of patients. Therefore, predicting potential DDI has always been an important and challenging issue in medical health applications. Owing to the extensive pharmacological research, we can get access to various drug-related features for DDI predictions; however, most of the existing works on DDI prediction do not incorporate comprehensive features to analyze the DDI patterns. Despite the high performance that the existing works have achieved, the incomplete and noisy information generated from limited sources usually leads to sub-optimal performance and poor generalization ability on the unknown DDI pairs. In this work, we propose a holistic framework, namely Multi-modality Feature Optimal Fusion for Drug-Drug Interaction Prediction (MOF-DDI), that incorporates the features from multiple data sources to resolve the DDI predictions. Specifically, the proposed model jointly considers DDIs literature descriptions, biomedical knowledge graphs, and drug molecular structures to make the prediction. To overcome the issue induced by directly aggregating features in different modalities, we bring a new insight by mapping the representations learned from different sources to a unified hidden space before the combination. The empirical results show that MOF-DDI achieves a large performance gain on different DDI datasets compared with multiple state-of-the-art baselines, especially under the inductive setting.

Graph structure learning (GSL), which aims to learn the adjacency matrix for graph neural networks (GNNs), has shown great potential in boosting the performance of GNNs. Most existing GSL works apply a joint learning framework where the estimated adjacency matrix and GNN parameters are optimized for downstream tasks. However, as GSL is essentially a link prediction task, whose goal may largely differ from the goal of the downstream task. The inconsistency of these two goals limits the GSL methods to learn the potential optimal graph structure. Moreover, the joint learning framework suffers from scalability issues in terms of time and space during the process of estimation and optimization of the adjacency matrix. To mitigate these issues, we propose a graph structure refinement (GSR) framework with a pretrain-finetune pipeline. Specifically, The pre-training phase aims to comprehensively estimate the underlying graph structure by a multi-view contrastive learning framework with both intra- and inter-view link prediction tasks. Then, the graph structure is refined by adding and removing edges according to the edge probabilities estimated by the pre-trained model. Finally, the fine-tuning GNN is initialized by the pre-trained model and optimized toward downstream tasks. With the refined graph structure remaining static in the fine-tuning space, GSR avoids estimating and optimizing graph structure in the fine-tuning phase which enjoys great scalability and efficiency. Moreover, the fine-tuning GNN is boosted by both migrating knowledge and refining graphs. Extensive experiments are conducted to evaluate the effectiveness (best performance on six benchmark datasets), efficiency, and scalability (13.8 times faster using 32.8% GPU memory compared to the best GSL baseline on Cora) of the proposed model.

Driven by the exponential increase of software and the advent of the pull-based development system Git, a large amount of open-source software has emerged on various social coding platforms. GitHub, as the largest platform, not only attracts developers and researchers to contribute legitimate software and research-related source code but has also become a popular platform for an increasing number of cybercriminals to perform continuous cyberattacks. Hence, some tools have been developed to learn representations of repositories on GitHub for various related applications (e.g., malicious repository detection) recently. However, most of them merely focus on code content while ignoring the rich relational data among repositories. In addition, they usually require a mass of resources to obtain sufficient labeled data for model training while ignoring the usefully handy unlabeled data. To this end, we propose a novel model Rep2Vec which integrates the code content, the structural relations, and the unlabeled data to learn the repository representations. First, to comprehensively model the repository data, we build a repository heterogeneous graph (Rep-HG) which is encoded by a graph neural network. Afterwards, to fully exploit unlabeled data in Rep-HG, we introduce adversarial attacks to generate more challenging contrastive pairs for the contrastive learning module to train the encoder in node view and meta-path view simultaneously. To alleviate the workload of the encoder against attacks, we further design a dual-stream contrastive learning module that integrates contrastive learning on adversarial graph and original graph together. Finally, the pre-trained encoder is fine-tuned to the downstream task, and further enhanced by a knowledge distillation module. Extensive experiments on the collected dataset from GitHub demonstrate the effectiveness of Rep2Vec in comparison with state-of-the-art methods for multiple repository tasks.

Opioids (e.g., oxycodone and morphine) are highly addictive prescription (aka Rx) drugs which can be easily overprescribed and lead to opioid overdose. Recently, the opioid epidemic is increasingly serious across the US as its related deaths have risen at alarming rates. To combat the deadly opioid epidemic, a state-run prescription drug monitoring program (PDMP) has been established to alleviate the drug over-prescribing problem in the US. Although PDMP provides a detailed prescription history related to opioids, it is still not enough to prevent opioid overdose because it cannot predict over-prescribing risk. In addition, existing machine learning-based methods mainly focus on drug doses while ignoring other prescribing patterns behind patients' historical records, thus resulting in suboptimal performance. To this end, we propose a novel model DDHGNN - Disentangled Dynamic Heterogeneous Graph Neural Network, for over-prescribing prediction. Specifically, we abstract the PDMP data into a dynamic heterogeneous graph which comprehensively depicts the prescribing and dispensing (P&D) relationships. Then, we design a dynamic heterogeneous graph neural network to learn patients' representations. Furthermore, we devise an adversarial disentangler to learn a disentangled representation which is particularly related to the prescribing patterns. Extensive experiments on a 1-year anonymous PDMP data demonstrate that DDHGNN outperforms state-of-the-art methods, revealing its promising future in preventing opioid overdose.

Prescription (aka Rx) drugs can be easily overprescribed and lead to drug abuse or opioid overdose. Accordingly, a state-run prescription drug monitoring program (PDMP) in the United States has been developed to reduce Overprescribing. However, PDMP has limited capability in detecting patients' potential overprescribing behaviors, impairing its effectiveness in preventing drug abuse and overdose in patients. Despite a few machine-learning-based methods that have been proposed for detecting overprescribing, they usually ignore the patient prescribing behavior and their performances are not satisfying. In light of this, we propose a novel model RxNet for overprescribing detection in PDMP. RxNet builds a dynamic heterogeneous graph to model Rx refills that are essentially prescribing and dispensing (P&D) relationships among various Rx entries (e.g., patients) whose representations are encoded by graph neural network. In addition, to explore the dynamic Rx-refill behavior and medical condition variation of patients, an RxLSTM network is designed to update representations of patients. Based on the output of RxLSTM, a dosing-adaptive network is leveraged to extract and recalibrate dosing patterns and obtain the refined patient representations which are finally utilized for overprescribing detection. The extensive experimental results on a 1-year Ohio PDMP data demonstrate that RxNet consistently outperforms state-of-the-art methods in predicting patients at high risk of opioid overdose and drug abuse, with an average of 5.7% and 7.3% improvement on F1 score respectively.