An empirical Bayesian approach for model-based inference of cellular signaling networks.
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.


CONCLUSIONS
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.
Klinke
David J
DJ
Department of Chemical Engineering, West Virginia University, Morgantown, WV 26506-6102, USA. david.klinke@mail.wvu.edu
D000818:Animals; D001499:Bayes Theorem; D019295:Computational Biology / Q000379:methods*; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D016571:Neural Networks, Computer; D051381:Rats; D015398:Signal Transduction
D004815:Epidermal Growth Factor