%0 Journal Article %J Sci Rep %D 2015 %T Using activation status of signaling pathways as mechanism-based biomarkers to predict drug sensitivity. %A Amadoz, Alicia %A Sebastián-Leon, Patricia %A Vidal, Enrique %A Salavert, Francisco %A Dopazo, Joaquin %K Algorithms %K Antineoplastic Agents %K biomarkers %K Cell Line, Tumor %K Cell Survival %K gene expression %K Humans %K Lethal Dose 50 %K Neoplasms %K Phosphorylation %K Proteins %K Signal Transduction %X

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).

%B Sci Rep %V 5 %P 18494 %8 2015 Dec 18 %G eng %1 https://www.ncbi.nlm.nih.gov/pubmed/26678097?dopt=Abstract %R 10.1038/srep18494