A Knowledge Graph-Enhanced Tensor Factorisation Model for Discovering Drug Targets

원문 초록

The drug discovery and development process is a long and expensive one, costing over 1 billion USD on average per drug and taking 10-15 years. To reduce the high levels of attrition throughout the process, there has been a growing interest in applying machine learning methodologies to various stages of drug discovery and development in the recent decade, especially at the earliest stage identification of druggable disease genes. In this paper, we have developed a new tensor factorisation model to predict potential drug targets (genes or proteins) for treating diseases. We created a three dimensional data tensor consisting of 1,048 gene targets, 860 diseases and 230,011 evidence attributes and clinical outcomes connecting them, using data extracted from the Open Targets and PharmaProjects databases. We enriched the data with gene target representations learned from a drug discovery oriented knowledge graph and applied our proposed method to predict the clinical outcomes for unseen gene target and disease pairs. We designed three evaluation strategies to measure the prediction performance and benchmarked several commonly used machine learning classifiers together with Bayesian matrix and tensor factorisation methods. The result shows that incorporating knowledge graph embeddings significantly improves the prediction accuracy and that training tensor factorisation alongside a dense neural network outperforms all other baselines. In summary, our framework combines two actively studied machine learning approaches to disease target identification, namely tensor factorisation and knowledge graph representation learning, which could be a promising avenue for further exploration in data driven drug discovery.