A Systematic Framework for Drug Repositioning from Integrated Omics and Drug Phenotype Profiles Using Pathway-Drug Network.

Drug repositioning offers new clinical indications for old drugs. Recently, many computational approaches have been developed to repurpose marketed drugs in human diseases by mining various of biological data including disease expression profiles, pathways, drug phenotype expression profiles, and ch...

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Published in:BioMed Research International Vol. 2016; pp. 1 - 18
Main Authors: Jadamba, Erkhembayar, Shin, Miyoung
Format: equations & formulas research tables/charts Journal Article
Published: Wiley-Blackwell 12/26/2016
Online Access:View this record in EBSCOhost
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      dt: 12/26/2016
      vid: 2016
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        10.1155/2016/7147039
        120387077
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        atl: A Systematic Framework for Drug Repositioning from Integrated Omics and Drug Phenotype Profiles Using Pathway-Drug Network.
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          Jadamba, Erkhembayar
          Shin, Miyoung
        affil: Bio-Intelligence & Data Mining Laboratory, Graduate School of Electrical Engineering and Computer Science, Kyungpook National University, 1370 Sangyeok-dong, Buk-gu, Daegu 702-701, Republic of Korea
      sug:
        subj:
          Conceptual Framework
          Drug Repositioning
          Drugs Therapeutic Use
          Phenotype
          Drug Evaluation
          Genome
          Gene Expression
          Breast Neoplasms Therapy
          Patient Selection
          Female
          Drug Design Methods
          Drugs, Investigational Economics
          Health Care Costs
          Drug Approval
          United States Food and Drug Administration
          Disease Physiopathology
          Validation Therapy
          Funding Source
          Female
      ab: Drug repositioning offers new clinical indications for old drugs. Recently, many computational approaches have been developed to repurpose marketed drugs in human diseases by mining various of biological data including disease expression profiles, pathways, drug phenotype expression profiles, and chemical structure data. However, despite encouraging results, a comprehensive and efficient computational drug repositioning approach is needed that includes the high-level integration of available resources. In this study, we propose a systematic framework employing experimental genomic knowledge and pharmaceutical knowledge to reposition drugs for a specific disease. Specifically, we first obtain experimental genomic knowledge from disease gene expression profiles and pharmaceutical knowledge from drug phenotype expression profiles and construct a pathway-drug network representing a priori known associations between drugs and pathways. To discover promising candidates for drug repositioning, we initialize node labels for the pathway-drug network using identified disease pathways and known drugs associated with the phenotype of interest and perform network propagation in a semisupervised manner. To evaluate our method, we conducted some experiments to reposition 1309 drugs based on four different breast cancer datasets and verified the results of promising candidate drugs for breast cancer by a two-step validation procedure. Consequently, our experimental results showed that the proposed framework is quite useful approach to discover promising candidates for breast cancer treatment.
      pubtype: Academic Journal
      doctype:
        equations & formulas
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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