Article (Scientific journals)
Identification of potential pathway mediation targets in Toll-like receptor signaling.
Li, Fan; Thiele, Ines; Jamshidi, Neema et al.
2009In PLoS Computational Biology, 5 (2), p. 1000292
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Keywords :
Cell Compartmentation/physiology; Feedback, Physiological; Humans; Models, Biological; Phosphorylation; Proteome/chemistry/metabolism; Signal Transduction/physiology; Toll-Like Receptors/agonists/antagonists & inhibitors/physiology
Abstract :
[en] 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.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Li, Fan
Thiele, Ines 
Jamshidi, Neema
Palsson, Bernhard O.
Language :
Title :
Identification of potential pathway mediation targets in Toll-like receptor signaling.
Publication date :
Journal title :
PLoS Computational Biology
Publisher :
Public Library of Science, United States - California
Volume :
Issue :
Pages :
Peer reviewed :
Peer Reviewed verified by ORBi
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since 12 December 2013


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