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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-02-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19229310/?tool=EBI |
| _version_ | 1818342302565793792 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-13T16:12:32Z |
| format | Article |
| id | doaj.art-7c7a56edbd534ff2b4ad606be741a5c8 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-13T16:12:32Z |
| publishDate | 2009-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-7c7a56edbd534ff2b4ad606be741a5c82022-12-21T23:38:54ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582009-02-0152e100029210.1371/journal.pcbi.1000292Identification of potential pathway mediation targets in Toll-like receptor signaling.Fan LiInes ThieleNeema JamshidiBernhard Ø PalssonRecent 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19229310/?tool=EBI |
| spellingShingle | Fan Li Ines Thiele Neema Jamshidi Bernhard Ø Palsson Identification of potential pathway mediation targets in Toll-like receptor signaling. PLoS Computational Biology |
| title | 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_short | Identification of potential pathway mediation targets in Toll-like receptor signaling. |
| title_sort | identification of potential pathway mediation targets in toll like receptor signaling |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19229310/?tool=EBI |
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