Drug repurposing with network reinforcement

Yonghyun Nam,Hang-Seok Chang,Hyunjung Shin,Myungjun Kim

doi:10.1186/s12859-019-2858-6

Yonghyun Nam, Hang-Seok Chang + Show 2 more

Open Access

https://doi.org/10.1186/s12859-019-2858-6

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Abstract

BackgroundDrug repurposing has been motivated to ameliorate low probability of success in drug discovery. For the recent decade, many in silico attempts have received primary attention as a first step to alleviate the high cost and longevity. Such study has taken benefits of abundance, variety, and easy accessibility of pharmaceutical and biomedical data. Utilizing the research friendly environment, in this study, we propose a network-based machine learning algorithm for drug repurposing. Particularly, we show a framework on how to construct a drug network, and how to strengthen the network by employing multiple/heterogeneous types of data.ResultsThe proposed method consists of three steps. First, we construct a drug network from drug-target protein information. Then, the drug network is reinforced by utilizing drug-drug interaction knowledge on bioactivity and/or medication from literature databases. Through the enhancement, the number of connected nodes and the number of edges between them become more abundant and informative, which can lead to a higher probability of success of in silico drug repurposing. The enhanced network recommends candidate drugs for repurposing through drug scoring. The scoring process utilizes graph-based semi-supervised learning to determine the priority of recommendations.ConclusionsThe drug network is reinforced in terms of the coverage and connections of drugs: the drug coverage increases from 4738 to 5442, and the drug-drug associations as well from 808,752 to 982,361. Along with the network enhancement, drug recommendation becomes more reliable: AUC of 0.89 was achieved lifted from 0.79. For typical cases, 11 recommended drugs were shown for vascular dementia: amantadine, conotoxin GV, tenocyclidine, cycloeucine, etc.

Highlights

Drug repurposing has been motivated to ameliorate low probability of success in drug discovery
The drug network is reinforced in terms of the coverage and connections of drugs: the drug coverage increases from 4738 to 5442, and the drug-drug associations as well from 808,752 to 982,361
11 recommended drugs were shown for vascular dementia: amantadine, conotoxin GV, tenocyclidine, cycloeucine, etc

Summary

Introduction

Drug repurposing has been motivated to ameliorate low probability of success in drug discovery. The whole process of de novo drug discovery takes 10 to 17 years for development with the cost rising from 300 to 600 million dollars [1]. There are three channels of approaches, in vitro, in vivo, and in silico, in drug repurposing. Compared to de novo drug discovery, in vitro, and in vivo approaches have advantage of reducing the development time, down to 3 to 12 years but they are only available with a good years of expertise on clinical and pharmaceutical domain [4,5,6]. To find new indicators for drugs, in silico approaches, on the other hand, attempt computational dry-runs that simulate and search all the possible combinations of drugs and diseases from databases which have been more available nowadays. One channel is not an alternative to others but rather complementary to each other, so it is accepted as a packaged

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