title: Actionable pathways: interactive discovery of therapeutic targets using signaling pathway models.
abstract: The discovery of actionable targets is crucial for targeted therapies and is also a constituent part of the drug discovery process. The success of an intervention over a target depends critically on its contribution, within the complex network of gene interactions, to the cellular processes responsible for disease progression or therapeutic response. Here we present PathAct, a web server that predicts the effect that interventions over genes (inhibitions or activations that simulate knock-outs, drug treatments or over-expressions) can have over signal transmission within signaling pathways and, ultimately, over the cell functionalities triggered by them. PathAct implements an advanced graphical interface that provides a unique interactive working environment in which the suitability of potentially actionable genes, that could eventually become drug targets for personalized or individualized therapies, can be easily tested. The PathAct tool can be found at: http://pathact.babelomics.org.
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, 46012, Spain Bioinformatics in Rare Diseases (BiER), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Valencia, 46012, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Salavert
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, 46012, Spain.
authors.forename: Marta R
authors.initials: MR
authors.lastname: Hidago
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, 46012, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Amadoz
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, 46012, Spain.
authors.forename: Cankut
authors.initials: C
authors.lastname: Çubuk
authors.affiliation: HPC Service, University Information Services, University of Cambridge, Cambridge, CB3 0RB, UK.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Medina
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, 46012, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Crespo
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, 46012, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Carbonell-Caballero
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, 46012, Spain Bioinformatics in Rare Diseases (BiER), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Valencia, 46012, Spain Functional Genomics Node, (INB, PRB2, ISCIII) at CIPF, Valencia 46012, Spain jdopazo@cipf.es.
authors.forename: Joaquín
authors.identifier: 0000-0003-3318-120X
authors.initials: J
authors.lastname: Dopazo
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003196:Computer Graphics; D003198:Computer Simulation; D055808:Drug Discovery; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D055786:Gene Knockout Techniques; D006801:Humans; D016247:Information Storage and Retrieval; D020407:Internet; D053858:Metabolic Networks and Pathways / Q000187:drug effects / Q000235:genetics; D015233:Models, Statistical; D058990:Molecular Targeted Therapy; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects*; D012984:Software; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib