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

TitleHigh throughput estimation of functional cell activities reveals disease mechanisms and predicts relevant clinical outcomes.
Publication TypeJournal Article
Year of Publication2017
AuthorsHidalgo MR, Cubuk C, Amadoz A, Salavert F, Carbonell-Caballero J, Dopazo J
Journal TitleOncotarget
Volume8
Pages5160-5178
Journal Date2017 Jan 17
ISSN1949-2553
Keywordsmodeling, RNA-seq, signalling pathways, Systems biology
AbstractUnderstanding 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.
URLhttp://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=14107&path%5B%5D=44984
DOI10.18632/oncotarget.14107
Alternate JournalOncotarget