High throughput estimation of functional cell activities reveals disease mechanisms and predicts relevant clinical outcomes.

ABSTRACT: 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

SUBMITTER: Hidalgo MR 

PROVIDER: S-EPMC5354899 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature