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

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. T...

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Autores principales:	Fan Li, Ines Thiele, Neema Jamshidi, Bernhard Ø Palsson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/7c7a56edbd534ff2b4ad606be741a5c8
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id	oai:doaj.org-article:7c7a56edbd534ff2b4ad606be741a5c8
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spelling	oai:doaj.org-article:7c7a56edbd534ff2b4ad606be741a5c82021-11-25T05:41:50ZIdentification of potential pathway mediation targets in Toll-like receptor signaling.1553-734X1553-735810.1371/journal.pcbi.1000292https://doaj.org/article/7c7a56edbd534ff2b4ad606be741a5c82009-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19229310/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Recent 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.Fan LiInes ThieleNeema JamshidiBernhard Ø PalssonPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 5, Iss 2, p e1000292 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Fan Li Ines Thiele Neema Jamshidi Bernhard Ø Palsson Identification of potential pathway mediation targets in Toll-like receptor signaling.
description	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.
format	article
author	Fan Li Ines Thiele Neema Jamshidi Bernhard Ø Palsson
author_facet	Fan Li Ines Thiele Neema Jamshidi Bernhard Ø Palsson
author_sort	Fan Li
title	Identification of potential pathway mediation targets in Toll-like receptor signaling.
title_short	Identification of potential pathway mediation targets in Toll-like receptor signaling.
title_full	Identification of potential pathway mediation targets in Toll-like receptor signaling.
title_fullStr	Identification of potential pathway mediation targets in Toll-like receptor signaling.
title_full_unstemmed	Identification of potential pathway mediation targets in Toll-like receptor signaling.
title_sort	identification of potential pathway mediation targets in toll-like receptor signaling.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/7c7a56edbd534ff2b4ad606be741a5c8
work_keys_str_mv	AT fanli identificationofpotentialpathwaymediationtargetsintolllikereceptorsignaling AT inesthiele identificationofpotentialpathwaymediationtargetsintolllikereceptorsignaling AT neemajamshidi identificationofpotentialpathwaymediationtargetsintolllikereceptorsignaling AT bernhardøpalsson identificationofpotentialpathwaymediationtargetsintolllikereceptorsignaling
_version_	1718414525947969536

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

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