Document Type
Article
Publication Date
2009
College/Unit
Statler College of Engineering and Mining Resources
Department/Program/Center
Chemical and Biomedical Engineering
Abstract
Background
A common challenge in systems biology is to infer mechanistic descriptions of biological process given limited observations of a biological system. Mathematical models are frequently used to represent a belief about the causal relationships among proteins within a signaling network. Bayesian methods provide an attractive framework for inferring the validity of those beliefs in the context of the available data. However, efficient sampling of high-dimensional parameter space and appropriate convergence criteria provide barriers for implementing an empirical Bayesian approach. The objective of this study was to apply an Adaptive Markov chain Monte Carlo technique to a typical study of cellular signaling pathways.
Results
As an illustrative example, a kinetic model for the early signaling events associated with the epidermal growth factor (EGF) signaling network was calibrated against dynamic measurements observed in primary rat hepatocytes. A convergence criterion, based upon the Gelman-Rubin potential scale reduction factor, was applied to the model predictions. The posterior distributions of the parameters exhibited complicated structure, including significant covariance between specific parameters and a broad range of variance among the parameters. The model predictions, in contrast, were narrowly distributed and were used to identify areas of agreement among a collection of experimental studies.
Conclusion
In summary, an empirical Bayesian approach was developed for inferring the confidence that one can place in a particular model that describes signal transduction mechanisms and for inferring inconsistencies in experimental measurements.
Digital Commons Citation
Klinke II, David J., "An empirical Bayesian approach for model-based inference of cellular signaling networks" (2009). Faculty & Staff Scholarship. 2831.
https://researchrepository.wvu.edu/faculty_publications/2831
Source Citation
Klinke, D.J. An empirical Bayesian approach for model-based inference of cellular signaling networks. BMC Bioinformatics 10, 371 (2009). https://doi.org/10.1186/1471-2105-10-371
Comments
© 2009 Klinke; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.