02839nas a2200397   4500008004100000022001400041245011600055210006900171260000900240300000600249490000600255520157600261653002601837653002401863653001901887653002901906653001101935653001301946653003601959653002301995653001402018653001402032653001302046653001802059100001802077700002202095700001902117700001602136700002402152700002202176700002102198700002002219700003102239700002002270856015102290       2019                        eng d  a2056-718900aDifferential metabolic activity and discovery of therapeutic targets using summarized metabolic pathway models.0 aDifferential metabolic activity and discovery of therapeutic tar  c2019  a70 v53 a<p>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.</p>10aComputational Biology10aComputer Simulation10aDrug discovery10aGene Regulatory Networks10aHumans10aInternet10aMetabolic Networks and Pathways10aModels, Biological10aNeoplasms10aPhenotype10aSoftware10aTranscriptome1 aCubuk, Cankut1 aHidalgo, Marta, R1 aAmadoz, Alicia1 aRian, Kinza1 aSalavert, Francisco1 aPujana, Miguel, A1 aMateo, Francesca1 aHerranz, Carmen1 aCarbonell-Caballero, José1 aDopazo, Joaquin  uhttps://www.clinbioinfosspa.es/content/differential-metabolic-activity-and-discovery-therapeutic-targets-using-summarized-metabolic-pathway-models