High-dimensional Bayesian parameter estimation: Case study for a model of JAK2/STAT5 signaling

- Bayesian inference of ODE signaling pathway model with more than 100 parameters.
- Combination of the profile likelihood/ posterior approach with MCMC sampling.
- Multi-chain approach guarantees efficient mixing in the presence of multimodality.
- Assessment of prediction uncertainties for dynamical key features of the pathway.
- Experimental design enhances the explanatory power of the mathematical model.

In this work we present results of a detailed Bayesian parameter estimation for an analysis of ordinary differential equation models. These depend on many unknown parameters that have to be inferred from experimental data. The statistical inference in a high-dimensional parameter space is however conceptually and computationally challenging. To ensure rigorous assessment of model and prediction uncertainties we take advantage of both a profile posterior approach and Markov chain Monte Carlo sampling.We analyzed a dynamical model of the JAK2/STAT5 signal transduction pathway that contains more than one hundred parameters. Using the profile posterior we found that the corresponding posterior distribution is bimodal. To guarantee efficient mixing in the presence of multimodal posterior distributions we applied a multi-chain sampling approach. The Bayesian parameter estimation enables the assessment of prediction uncertainties and the design of additional experiments that enhance the explanatory power of the model.This study represents a proof of principle that detailed statistical analysis for quantitative dynamical modeling used in systems biology is feasible also in high-dimensional parameter spaces.