RRC ID 59687
Author Çubuk C, Hidalgo MR, Amadoz A, Rian K, Salavert F, Pujana MA, Mateo F, Herranz C, Carbonell-Caballero J, Dopazo J.
Title Differential metabolic activity and discovery of therapeutic targets using summarized metabolic pathway models.
Journal NPJ Syst Biol Appl
Abstract In spite of the increasing availability of genomic and transcriptomic data, there is still a gap between the detection of perturbations in gene expression and the understanding of their contribution to the molecular mechanisms that ultimately account for the phenotype studied. Alterations in the metabolism are behind the initiation and progression of many diseases, including cancer. The wealth of available knowledge on metabolic processes can therefore be used to derive mechanistic models that link gene expression perturbations to changes in metabolic activity that provide relevant clues on molecular mechanisms of disease and drug modes of action (MoA). In particular, pathway modules, which recapitulate the main aspects of metabolism, are especially suitable for this type of modeling. We present Metabolizer, a web-based application that offers an intuitive, easy-to-use interactive interface to analyze differences in pathway metabolic module activities that can also be used for class prediction and in silico prediction of knock-out (KO) effects. Moreover, Metabolizer can automatically predict the optimal KO intervention for restoring a diseased phenotype. We provide different types of validations of some of the predictions made by Metabolizer. Metabolizer is a web tool that allows understanding molecular mechanisms of disease or the MoA of drugs within the context of the metabolism by using gene expression measurements. In addition, this tool automatically suggests potential therapeutic targets for individualized therapeutic interventions.
Volume 5
Pages 7
Published 2019-1-1
DOI 10.1038/s41540-019-0087-2
PII 10.1038/s41540-019-0087-2
PMID 30854222
PMC PMC6397295
MeSH Computational Biology / methods* Computer Simulation Drug Discovery / methods* Gene Regulatory Networks / genetics Humans Internet Metabolic Networks and Pathways / drug effects* Metabolic Networks and Pathways / genetics Metabolic Networks and Pathways / physiology Models, Biological Neoplasms / drug therapy Neoplasms / genetics Neoplasms / metabolism Phenotype Software Transcriptome
Times Cited 6
Resource
Human and Animal Cells TUHR4TKB(RCB1198)