Identification of potential pathway mediation targets in Toll-like receptor signaling.

TitleIdentification of potential pathway mediation targets in Toll-like receptor signaling.
Publication TypeJournal Article
Year of Publication2009
AuthorsLi F, Thiele I, Jamshidi N, Palsson BØ
JournalPLoS Comput Biol
Volume5
Issue2
Paginatione1000292
Date Published2009 Feb
ISSN1553-7358
KeywordsCell Compartmentation, Feedback, Physiological, Humans, Models, Biological, Phosphorylation, Proteome, Signal Transduction, Toll-Like Receptors
Abstract

Recent advances in reconstruction and analytical methods for signaling networks have spurred the development of large-scale models that incorporate fully functional and biologically relevant features. An extended reconstruction of the human Toll-like receptor signaling network is presented herein. This reconstruction contains an extensive complement of kinases, phosphatases, and other associated proteins that mediate the signaling cascade along with a delineation of their associated chemical reactions. A computational framework based on the methods of large-scale convex analysis was developed and applied to this network to characterize input-output relationships. The input-output relationships enabled significant modularization of the network into ten pathways. The analysis identified potential candidates for inhibitory mediation of TLR signaling with respect to their specificity and potency. Subsequently, we were able to identify eight novel inhibition targets through constraint-based modeling methods. The results of this study are expected to yield meaningful avenues for further research in the task of mediating the Toll-like receptor signaling network and its effects.

DOI10.1371/journal.pcbi.1000292
PubMed URLhttp://www.ncbi.nlm.nih.gov/pubmed/19229310?dopt=Abstract
PMCPMC2634968
Alternate JournalPLoS Comput. Biol.
PubMed ID19229310