title: Using activation status of signaling pathways as mechanism-based biomarkers to predict drug sensitivity.
abstract: Many complex traits, as drug response, are associated with changes in biological pathways rather than being caused by single gene alterations. Here, a predictive framework is presented in which gene expression data are recoded into activity statuses of signal transduction circuits (sub-pathways within signaling pathways that connect receptor proteins to final effector proteins that trigger cell actions). Such activity values are used as features by a prediction algorithm which can efficiently predict a continuous variable such as the IC50 value. The main advantage of this prediction method is that the features selected by the predictor, the signaling circuits, are themselves rich-informative, mechanism-based biomarkers which provide insight into or drug molecular mechanisms of action (MoA).
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Amadoz
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Sebastian-Leon
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.|Bioinformatics of Rare Diseases (BIER), CIBER de Enfermedades Raras (CIBERER), Valencia, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Vidal
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.|Bioinformatics of Rare Diseases (BIER), CIBER de Enfermedades Raras (CIBERER), Valencia, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Salavert
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.|Bioinformatics of Rare Diseases (BIER), CIBER de Enfermedades Raras (CIBERER), Valencia, Spain.|Functional Genomics Node, (INB) at CIPF, Valencia, Spain.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Dopazo
mesh_terms: D000465:Algorithms; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007928:Lethal Dose 50; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D011506:Proteins