Collaborating Authors

How AWS uses graph neural networks to meet customer needs


Graphs are an information-rich way to represent data. A graph consists of nodes -- typically represented by circles -- and edges -- typically represented as line segments between nodes. In a knowledge graph, for instance, the nodes represent entities, and the edges represent relationships between them. In a social graph, the nodes represent people, and an edge indicates that two of those people know each other. At Amazon Web Services, the use of machine learning (ML) to make the information encoded in graphs more useful to our customers has been a major research focus.

Modeling polypharmacy side effects with graph convolutional networks Machine Learning

The use of multiple drugs, termed polypharmacy, is common to treat patients with complex diseases or co-existing medical conditions. However, a major consequence of polypharmacy is a much higher risk of side effects for the patient. Polypharmacy side effects emerge because of drug interactions, in which activity of one drug may change, favorably or unfavorably, if taken with another drug. The knowledge of drug interactions is limited because these complex relationships are usually not observed in small clinical testing. Discovering polypharmacy side effects thus remains a challenge with significant implications for patient mortality and morbidity. Here we introduce Decagon, an approach for modeling polypharmacy side effects. The approach constructs a multimodal graph of protein-protein interactions, drug-protein interactions, and the polypharmacy side effects, which are represented as drug-drug interactions, where each side effect is an edge of a different type. Decagon is developed specifically to handle such multimodal graphs with a large number of edge types. Our approach develops a new graph convolutional neural network for multirelational link prediction in multimodal networks. Unlike approaches limited to predicting simple drug-drug interaction values, Decagon can predict the exact side effect, if any, through which a given drug combination manifests clinically. Decagon accurately predicts polypharmacy side effects, outperforming baselines by up to 69%. Furthermore, Decagon models particularly well side effects that have a strong molecular basis, while on predominantly non-molecular side effects, it achieves good performance because of effective sharing of model parameters across edge types. Decagon creates an opportunity to use large molecular and patient population data to flag and prioritize polypharmacy side effects for follow-up analysis via formal pharmacological studies.

TrialGraph: Machine Intelligence Enabled Insight from Graph Modelling of Clinical Trials Artificial Intelligence

A major impediment to successful drug development is the complexity, cost, and scale of clinical trials. The detailed internal structure of clinical trial data can make conventional optimization difficult to achieve. Recent advances in machine learning, specifically graph-structured data analysis, have the potential to enable significant progress in improving the clinical trial design. TrialGraph seeks to apply these methodologies to produce a proof-of-concept framework for developing models which can aid drug development and benefit patients. In this work, we first introduce a curated clinical trial data set compiled from the, AACT and TrialTrove databases (n=1191 trials; representing one million patients) and describe the conversion of this data to graph-structured formats. We then detail the mathematical basis and implementation of a selection of graph machine learning algorithms, which typically use standard machine classifiers on graph data embedded in a low-dimensional feature space. We trained these models to predict side effect information for a clinical trial given information on the disease, existing medical conditions, and treatment. The MetaPath2Vec algorithm performed exceptionally well, with standard Logistic Regression, Decision Tree, Random Forest, Support Vector, and Neural Network classifiers exhibiting typical ROC-AUC scores of 0.85, 0.68, 0.86, 0.80, and 0.77, respectively. Remarkably, the best performing classifiers could only produce typical ROC-AUC scores of 0.70 when trained on equivalent array-structured data. Our work demonstrates that graph modelling can significantly improve prediction accuracy on appropriate datasets. Successive versions of the project that refine modelling assumptions and incorporate more data types can produce excellent predictors with real-world applications in drug development.

Drug-disease Graph: Predicting Adverse Drug Reaction Signals via Graph Neural Network with Clinical Data Machine Learning

Adverse Drug Reaction (ADR) is a significant public health concern world-wide. Numerous graph-based methods have been applied to biomedical graphs for predicting ADRs in pre-marketing phases. ADR detection in post-market surveillance is no less important than pre-marketing assessment, and ADR detection with large-scale clinical data have attracted much attention in recent years. However, there are not many studies considering graph structures from clinical data for detecting an ADR signal, which is a pair of a prescription and a diagnosis that might be a potential ADR. In this study, we develop a novel graph-based framework for ADR signal detection using healthcare claims data. We construct a Drug-disease graph with nodes representing the medical codes. The edges are given as the relationships between two codes, computed using the data. We apply Graph Neural Network to predict ADR signals, using labels from the Side Effect Resource database. The model shows improved AUROC and AUPRC performance of 0.795 and 0.775, compared to other algorithms, showing that it successfully learns node representations expressive of those relationships. Furthermore, our model predicts ADR pairs that do not exist in the established ADR database, showing its capability to supplement the ADR database.

Drug Similarity Integration Through Attentive Multi-view Graph Auto-Encoders Machine Learning

Drug similarity has been studied to support downstream clinical tasks such as inferring novel properties of drugs (e.g. side effects, indications, interactions) from known properties. The growing availability of new types of drug features brings the opportunity of learning a more comprehensive and accurate drug similarity that represents the full spectrum of underlying drug relations. However, it is challenging to integrate these heterogeneous, noisy, nonlinear-related information to learn accurate similarity measures especially when labels are scarce. Moreover, there is a trade-off between accuracy and interpretability. In this paper, we propose to learn accurate and interpretable similarity measures from multiple types of drug features. In particular, we model the integration using multi-view graph auto-encoders, and add attentive mechanism to determine the weights for each view with respect to corresponding tasks and features for better interpretability. Our model has flexible design for both semi-supervised and unsupervised settings. Experimental results demonstrated significant predictive accuracy improvement. Case studies also showed better model capacity (e.g. embed node features) and interpretability.