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Bayesian modeling suggests that IL-12 (p40), IL-13 and MCP-1 drive murine cytokine networks in vivo
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Field, Sarah L., Dasgupta, Tathagata, Cummings, Michele, Savage, Richard S., Adebayo, Julius, McSara, Hema, Gunawardena, Jeremy and Orsi, Nicolas M. (2015) Bayesian modeling suggests that IL-12 (p40), IL-13 and MCP-1 drive murine cytokine networks in vivo. BMC Systems Biology, 9 (46). pp. 1-22. doi:10.1186/s12918-015-0226-3 ISSN 1752-0509.
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Official URL: http://dx.doi.org/10.1186/s12918-015-0226-3
Abstract
Background:
Cytokine-hormone network deregulations underpin pathologies ranging from autoimmune disorders to cancer, but our understanding of these networks in physiological/pathophysiological states remains patchy. We employed Bayesian networks to analyze cytokine-hormone interactions in vivo using murine lactation as a dynamic, physiological model system.
Results:
Circulatory levels of estrogen, progesterone, prolactin and twenty-three cytokines were profiled in post partum mice with/without pups. The resultant networks were very robust and assembled about structural hubs, with evidence that interleukin (IL)-12 (p40), IL-13 and monocyte chemoattractant protein (MCP)-1 were the primary drivers of network behavior. Network structural conservation across physiological scenarios coupled with the successful empirical validation of our approach suggested that in silico network perturbations can predict in vivo qualitative responses. In silico perturbation of network components also captured biological features of cytokine interactions (antagonism, synergy, redundancy).
Conclusion:
These findings highlight the potential of network-based approaches in identifying novel cytokine pharmacological targets and in predicting the effects of their exogenous manipulation in inflammatory/immune disorders.
| Item Type: | Journal Article | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Subjects: | R Medicine > RM Therapeutics. Pharmacology | ||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Statistics Faculty of Science, Engineering and Medicine > Research Centres > Warwick Systems Biology Centre |
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| Library of Congress Subject Headings (LCSH): | Cytokines, Lactation | ||||||||
| Journal or Publication Title: | BMC Systems Biology | ||||||||
| Publisher: | BioMed Central Ltd. | ||||||||
| ISSN: | 1752-0509 | ||||||||
| Official Date: | 9 November 2015 | ||||||||
| Dates: |
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| Volume: | 9 | ||||||||
| Number: | 46 | ||||||||
| Number of Pages: | 22 | ||||||||
| Page Range: | pp. 1-22 | ||||||||
| DOI: | 10.1186/s12918-015-0226-3 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Open Access (Creative Commons) |
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