Abstract

The prevalence of Parkinson’s disease increases a tremendous medical and economic burden to society. Therefore, the effective drugs are urgently required. However, the traditional development of effective drugs is costly and risky. Drug repurposing, which identifies new applications for existing drugs, is a feasible strategy for discovering new drugs for Parkinson’s disease. Drug repurposing is based on sufficient medical knowledge. The local medical knowledge base with manually labeled data contains a large number of accurate, but not novel, medical knowledge, while the medical literature containing the latest knowledge is difficult to utilize, because of unstructured data. This paper proposes a framework, named Drug Repurposing for Parkinson’s disease by integrating Knowledge Graph Completion method and Knowledge Fusion of medical literature data (DRKF) in order to make full use of a local medical knowledge base containing accurate knowledge and medical literature with novel knowledge. DRKF first extracts the relations that are related to Parkinson’s disease from medical literature and builds a medical literature knowledge graph. After that, the literature knowledge graph is fused with a local medical knowledge base that integrates several specific medical knowledge sources in order to construct a fused medical knowledge graph. Subsequently, knowledge graph completion methods are leveraged to predict the drug candidates for Parkinson’s disease by using the fused knowledge graph. Finally, we employ classic machine learning methods to repurpose the drug for Parkinson’s disease and compare the results with the method only using the literature-based knowledge graph in order to confirm the effectiveness of knowledge fusion. The experiment results demonstrate that our framework can achieve competitive performance, which confirms the effectiveness of our proposed DRKF for drug repurposing against Parkinson’s disease. It could be a supplement to traditional drug discovery methods.

Highlights

  • Parkinson’s disease is a neurodegenerative disease that occurs more frequently in the elderly

  • This paper further explores the drug repurposing research of Parkinson’s disease integrating knowledge fusion and knowledge graph completion method

  • In the task of knowledge graph completion methods, drug repurposing is considered to be a task of predicting missing medical entities for given triples like the form of (?, TREAT, Parkinson’s disease)

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Summary

Introduction

Parkinson’s disease is a neurodegenerative disease that occurs more frequently in the elderly. It is very urgent to develop effective drugs to treat Parkinson’s disease. In view of the good effects of dopaminergic medications on Parkinson’s disease and the slowing of the pathogenesis of Parkinson’s disease [1], the exploration of levodopa drugs is the mainstream research direction for the treatment of Parkinson’s disease. This method has the disadvantage that the long-term use of this drug will cause motor complications of patients [2].

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