Abstract
BackgroundTraditional drug research and development is high cost, time-consuming and risky. Computationally identifying new indications for existing drugs, referred as drug repositioning, greatly reduces the cost and attracts ever-increasing research interests. Many network-based methods have been proposed for drug repositioning and most of them apply random walk on a heterogeneous network consisted with disease and drug nodes. However, these methods generally adopt the same walk-length for all nodes, and ignore the different contributions of different nodes.ResultsIn this study, we propose a drug repositioning approach based on individual bi-random walks (DR-IBRW) on the heterogeneous network. DR-IBRW firstly quantifies the individual work-length of random walks for each node based on the network topology and knowledge that similar drugs tend to be associated with similar diseases. To account for the inner structural difference of the heterogeneous network, it performs bi-random walks with the quantified walk-lengths, and thus to identify new indications for approved drugs. Empirical study on public datasets shows that DR-IBRW achieves a much better drug repositioning performance than other related competitive methods.ConclusionsUsing individual random walk-lengths for different nodes of heterogeneous network indeed boosts the repositioning performance. DR-IBRW can be easily generalized to prioritize links between nodes of a network.
Highlights
Traditional drug research and development is high cost, time-consuming and risky
We propose a novel drug repositioning approach that performs bi-random walk with restart on a heterogeneous network with quantified individual walk-length for each node
It quantifies the individual walk-length for each node based on the topology of known drug-disease association network. It constructs a heterogeneous network based on these three networks. It performs bi-random walks with the quantified walk-lengths to account for the structural differences of these networks and contribution differences of different nodes, and to predict new associations between drugs and diseases, and to accomplish the drug repositioning
Summary
We propose a drug repositioning approach based on individual bi-random walks (DR-IBRW) on the heterogeneous network. DR-IBRW firstly quantifies the individual work-length of random walks for each node based on the network topology and knowledge that similar drugs tend to be associated with similar diseases. To account for the inner structural difference of the heterogeneous network, it performs bi-random walks with the quantified walk-lengths, and to identify new indications for approved drugs. Empirical study on public datasets shows that DR-IBRW achieves a much better drug repositioning performance than other related competitive methods
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