RT Journal Article SR Electronic T1 High throughput estimation of functional cell activities reveals disease mechanisms and predicts relevant clinical outcomes JF bioRxiv FD Cold Spring Harbor Laboratory SP 076083 DO 10.1101/076083 A1 Marta R. Hidalgo A1 Cankut Cubuk A1 Alicia Amadoz A1 Francisco Salavert A1 José Carbonell-Caballero A1 Joaquin Dopazo YR 2016 UL http://biorxiv.org/content/early/2016/09/19/076083.abstract AB Understanding the aspects of the cell functionality that account for disease or drug action mechanisms is a main challenge for precision medicine. Here we propose a new method that models cell signaling using biological knowledge on signal transduction. The method recodes individual gene expression values (and/or gene mutations) into accurate measurements of changes in the activity of signaling circuits, which ultimately constitute high-throughput estimations of cell functionalities caused by gene activity within the pathway. Moreover, such estimations can be obtained either at cohort-level, in case/control comparisons, or personalized for individual patients. The accuracy of the method is demonstrated in an extensive analysis involving 5640 patients from 12 different cancer types. Circuit activity measurements not only have a high diagnostic value but also can be related to relevant disease outcomes such as survival, and can be used to assess therapeutic interventions.