A bidirectional drug repositioning approach for Parkinson's disease through network-based inference

• Published in: Biochemical and biophysical research communications 2015-02, Vol.457 (3), p.280-287
• Main Authors: Rakshit, Hindol, Chatterjee, Paulami, Roy, Debjani
• Format: Article
• Language: English
• Subjects: Antiparkinson Agents - chemistry; Antiparkinson Agents - therapeutic use; Computational Biology; Databases, Genetic; Databases, Pharmaceutical; Drug repositioning; Drug Repositioning - methods; Drug Repositioning - statistics & numerical data; Genetic Markers; Humans; Indication-drug-target network; Parkinson Disease - drug therapy; Parkinson Disease - genetics; Parkinson Disease - metabolism; Parkinson's disease; Protein Interaction Maps; Protein–protein interaction network; Topological significance
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2014.12.101

Parkinson's Disease (PD) is one of the most prevailing neurodegenerative disorders. Novel computational approaches are required to find new ways of using the existing drugs or drug repositioning, as currently there exists no cure for PD. We proposed a new bidirectional drug repositioning method that consists of Top-down and Bottom-up approaches and finally gives information about significant repositioning drug candidates. This method takes into account of the topological significance of drugs in the tripartite Indication-drug-target network (IDTN) as well the significance of their targets in the PD-specific protein–protein interaction network (PPIN). 9 non-Parkinsonian drugs have been proposed as the significant repositioning candidates for PD. In order to find out the efficiency of the repositioning candidates we introduced a parameter called the On-target ratio (OTR). The average OTR value of final repositioning candidates has been found to be higher than that of known PD specific drugs. •Developed novel supervised inference method for network-based drug repositioning.•This method consists of a new bidirectional Top-down and Bottom-up approaches.•Topologically significant nodes in both drug and protein networks are considered.•9 significant repositioning drugs for PD are identified.