Journal
BIOINFORMATICS
Volume 29, Issue 10, Pages 1283-1291Publisher
OXFORD UNIV PRESS
DOI: 10.1093/bioinformatics/btt130
Keywords
-
Categories
Funding
- Academy of Finland (Centre of Excellence in Molecular Systems Immunology and Physiology Research) [135320, 259038]
- EU [EC-FP7-SYBILLA-201106]
- EU ERASysBio ERA-NET
- FICS graduate school
- Academy of Finland (AKA) [259038, 135320, 135320, 259038] Funding Source: Academy of Finland (AKA)
Ask authors/readers for more resources
Motivation: Signaling networks mediate responses to different stimuli using a multitude of feed-forward, feedback and cross-talk mechanisms, and malfunctions in these mechanisms have an important role in various diseases. To understand a disease and to help discover novel therapeutic approaches, we have to reveal the molecular mechanisms underlying signal transduction and use that information to design targeted perturbations. Results: We have pursued this direction by developing an efficient computational approach, Sorad, which can estimate the structure of signal transduction networks and the associated continuous signaling dynamics from phosphoprotein time-course measurements. Further, Sorad can identify experimental conditions that modulate the signaling toward a desired response. We have analyzed comprehensive phosphoprotein time-course data from a human hepatocellular liver carcinoma cell line and demonstrate here that Sorad provides more accurate predictions of phosphoprotein responses to given stimuli than previously presented methods and, importantly, that Sorad can estimate experimental conditions to achieve a desired signaling response. Because Sorad is data driven, it has a high potential to generate novel hypotheses for further research. Our analysis of the hepatocellular liver carcinoma data predict a regulatory connection where AKT activity is dependent on IKK in TGF alpha stimulated cells, which is supported by the original data but not included in the original model.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available