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Register a new userInterpretable Drug Synergy Prediction with Graph Neural Networks for Human-AI Collaboration in Healthcare
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Added by
Zehao Dong
Publication date
2021
fields
Informatics Engineering
and research's language is
English
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We investigate molecular mechanisms of resistant or sensitive response of cancer drug combination therapies in an inductive and interpretable manner. Though deep learning algorithms are widely used in the drug synergy prediction problem, it is still an open problem to formulate the prediction model with biological meaning to investigate the mysterious mechanisms of synergy (MoS) for the human-AI collaboration in healthcare systems. To address the challenges, we propose a deep graph neural network, IDSP (Interpretable Deep Signaling Pathways), to incorporate the gene-gene as well as gene-drug regulatory relationships in synergic drug combination predictions. IDSP automatically learns weights of edges based on the gene and drug node relations, i.e., signaling interactions, by a multi-layer perceptron (MLP) and aggregates information in an inductive manner. The proposed architecture generates interpretable drug synergy prediction by detecting important signaling interactions, and can be implemented when the underlying molecular mechanism encounters unseen genes or signaling pathways. We test IDWSP on signaling networks formulated by genes from 46 core cancer signaling pathways and drug combinations from NCI ALMANAC drug combination screening data. The experimental results demonstrated that 1) IDSP can learn from the underlying molecular mechanism to make prediction without additional drug chemical information while achieving highly comparable performance with current state-of-art methods; 2) IDSP show superior generality and flexibility to implement the synergy prediction task on both transductive tasks and inductive tasks. 3) IDSP can generate interpretable results by detecting different salient signaling patterns (i.e. MoS) for different cell lines.
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Sampling is an established technique to scale graph neural networks to large graphs. Current approaches however assume the graphs to be homogeneous in terms of relations and ignore relation types, critically important in biomedical graphs. Multi-relational graphs contain various types of relations that usually come with variable frequency and have different importance for the problem at hand. We propose an approach to modeling the importance of relation types for neighborhood sampling in graph neural networks and show that we can learn the right balance: relation-type probabilities that reflect both frequency and importance. Our experiments on drug-drug interaction prediction show that state-of-the-art graph neural networks profit from relation-dependent sampling in terms of both accuracy and efficiency.
We introduce Bi-GNN for modeling biological link prediction tasks such as drug-drug interaction (DDI) and protein-protein interaction (PPI). Taking drug-drug interaction as an example, existing methods using machine learning either only utilize the link structure between drugs without using the graph representation of each drug molecule, or only leverage the individual drug compound structures without using graph structure for the higher-level DDI graph. The key idea of our method is to fundamentally view the data as a bi-level graph, where the highest level graph represents the interaction between biological entities (interaction graph), and each biological entity itself is further expanded to its intrinsic graph representation (representation graphs), where the graph is either flat like a drug compound or hierarchical like a protein with amino acid level graph, secondary structure, tertiary structure, etc. Our model not only allows the usage of information from both the high-level interaction graph and the low-level representation graphs, but also offers a baseline for future research opportunities to address the bi-level nature of the data.
Travel-time prediction constitutes a task of high importance in transportation networks, with web mapping services like Google Maps regularly serving vast quantities of travel time queries from users and enterprises alike. Further, such a task requires accounting for complex spatiotemporal interactions (modelling both the topological properties of the road network and anticipating events -- such as rush hours -- that may occur in the future). Hence, it is an ideal target for graph representation learning at scale. Here we present a graph neural network estimator for estimated time of arrival (ETA) which we have deployed in production at Google Maps. While our main architecture consists of standard GNN building blocks, we further detail the usage of training schedule methods such as MetaGradients in order to make our model robust and production-ready. We also provide prescriptive studies: ablating on various architectural decisions and training regimes, and qualitative analyses on real-world situations where our model provides a competitive edge. Our GNN proved powerful when deployed, significantly reducing negative ETA outcomes in several regions compared to the previous production baseline (40+% in cities like Sydney).
Motivation: Predicting Drug-Target Interaction (DTI) is a well-studied topic in bioinformatics due to its relevance in the fields of proteomics and pharmaceutical research. Although many machine learning methods have been successfully applied in this task, few of them aim at leveraging the inherent heterogeneous graph structure in the DTI network to address the challenge. For better learning and interpreting the DTI topological structure and the similarity, it is desirable to have methods specifically for predicting interactions from the graph structure. Results: We present an end-to-end framework, DTI-GAT (Drug-Target Interaction prediction with Graph Attention networks) for DTI predictions. DTI-GAT incorporates a deep neural network architecture that operates on graph-structured data with the attention mechanism, which leverages both the interaction patterns and the features of drug and protein sequences. DTI-GAT facilitates the interpretation of the DTI topological structure by assigning different attention weights to each node with the self-attention mechanism. Experimental evaluations show that DTI-GAT outperforms various state-of-the-art systems on the binary DTI prediction problem. Moreover, the independent study results further demonstrate that our model can be generalized better than other conventional methods. Availability: The source code and all datasets are available at https://github.com/Haiyang-W/DTI-GRAPH
Drug-drug interaction(DDI) prediction is an important task in the medical health machine learning community. This study presents a new method, multi-view graph contrastive representation learning for drug-drug interaction prediction, MIRACLE for brevity, to capture inter-view molecule structure and intra-view interactions between molecules simultaneously. MIRACLE treats a DDI network as a multi-view graph where each node in the interaction graph itself is a drug molecular graph instance. We use GCNs and bond-aware attentive message passing networks to encode DDI relationships and drug molecular graphs in the MIRACLE learning stage, respectively. Also, we propose a novel unsupervised contrastive learning component to balance and integrate the multi-view information. Comprehensive experiments on multiple real datasets show that MIRACLE outperforms the state-of-the-art DDI prediction models consistently.
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