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Bayesian modeling suggests that IL-12 (p40), IL-13 and MCP-1 drive murine cytokine networks in vivo
- Source :
- BMC Systems Biology
- Publication Year :
- 2015
-
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. Electronic supplementary material The online version of this article (doi:10.1186/s12918-015-0226-3) contains supplementary material, which is available to authorized users.
- Subjects :
- RM
Mouse
Systems biology
medicine.medical_treatment
In silico
Biology
Models, Biological
Mice
Structural Biology
In vivo
Modelling and Simulation
medicine
Animals
Lactation
Protein Interaction Maps
Molecular Biology
Cytokine
Chemokine CCL2
Interleukin-13
Applied Mathematics
Postpartum Period
Interleukin
Bayes Theorem
Interleukin-12
Hormone
Hormones
Computer Science Applications
Bayesian network
Modeling and Simulation
Interleukin 13
Immunology
Interleukin 12
Cytokines
Female
Neuroscience
Postpartum period
Research Article
Subjects
Details
- ISSN :
- 17520509
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- BMC systems biology
- Accession number :
- edsair.doi.dedup.....b57874874d1bee652f7726e073c3c894