Back to Search
Start Over
Homologous Control of Protein Signaling Networks
- Source :
- Journal of Theoretical Biology 279 (2011) 29-43
- Publication Year :
- 2010
-
Abstract
- In a previous paper we introduced a method called augmented sparse reconstruction (ASR) that identifies links among nodes of ordinary differential equation networks, given a small set of observed trajectories with various initial conditions. The main purpose of that technique was to reconstruct intracellular protein signaling networks. In this paper we show that a recursive augmented sparse reconstruction generates artificial networks that are homologous to a large, reference network, in the sense that kinase inhibition of several reactions in the network alters the trajectories of a sizable number of proteins in comparable ways for reference and reconstructed networks. We show this result using a large in-silico model of the epidermal growth factor receptor (EGF-R) driven signaling cascade to generate the data used in the reconstruction algorithm. The most significant consequence of this observed homology is that a nearly optimal combinatorial dosage of kinase inhibitors can be inferred, for many nodes, from the reconstructed network, a result potentially useful for a variety of applications in personalized medicine.<br />Comment: 33 pages, 6 figures
Details
- Database :
- arXiv
- Journal :
- Journal of Theoretical Biology 279 (2011) 29-43
- Publication Type :
- Report
- Accession number :
- edsarx.1012.5547
- Document Type :
- Working Paper
- Full Text :
- https://doi.org/10.1016/j.jtbi.2011.03.020