TY - JOUR
T1 - Automated parameter estimation for biological models using Bayesian statistical model checking
AU - Hussain, Faraz
AU - Langmead, Christopher J.
AU - Mi, Qi
AU - Dutta-Moscato, Joyeeta
AU - Vodovotz, Yoram
AU - Jha, Sumit K.
N1 - Publisher Copyright:
© 2015 Hussain et al.
PY - 2015/12/7
Y1 - 2015/12/7
N2 - Background: Probabilistic models have gained widespread acceptance in the systems biology community as a useful way to represent complex biological systems. Such models are developed using existing knowledge of the structure and dynamics of the system, experimental observations, and inferences drawn from statistical analysis of empirical data. A key bottleneck in building such models is that some system variables cannot be measured experimentally. These variables are incorporated into the model as numerical parameters. Determining values of these parameters that justify existing experiments and provide reliable predictions when model simulations are performed is a key research problem. Domain experts usually estimate the values of these parameters by fitting the model to experimental data. Model fitting is usually expressed as an optimization problem that requires minimizing a cost-function which measures some notion of distance between the model and the data. This optimization problem is often solved by combining local and global search methods that tend to perform well for the specific application domain. When some prior information about parameters is available, methods such as Bayesian inference are commonly used for parameter learning. Choosing the appropriate parameter search technique requires detailed domain knowledge and insight into the underlying system. Results: Using an agent-based model of the dynamics of acute inflammation, we demonstrate a novel parameter estimation algorithm by discovering the amount and schedule of doses of bacterial lipopolysaccharide that guarantee a set of observed clinical outcomes with high probability. We synthesized values of twenty-eight unknown parameters such that the parameterized model instantiated with these parameter values satisfies four specifications describing the dynamic behavior of the model. Conclusions: We have developed a new algorithmic technique for discovering parameters in complex stochastic models of biological systems given behavioral specifications written in a formal mathematical logic. Our algorithm uses Bayesian model checking, sequential hypothesis testing, and stochastic optimization to automatically synthesize parameters of probabilistic biological models.
AB - Background: Probabilistic models have gained widespread acceptance in the systems biology community as a useful way to represent complex biological systems. Such models are developed using existing knowledge of the structure and dynamics of the system, experimental observations, and inferences drawn from statistical analysis of empirical data. A key bottleneck in building such models is that some system variables cannot be measured experimentally. These variables are incorporated into the model as numerical parameters. Determining values of these parameters that justify existing experiments and provide reliable predictions when model simulations are performed is a key research problem. Domain experts usually estimate the values of these parameters by fitting the model to experimental data. Model fitting is usually expressed as an optimization problem that requires minimizing a cost-function which measures some notion of distance between the model and the data. This optimization problem is often solved by combining local and global search methods that tend to perform well for the specific application domain. When some prior information about parameters is available, methods such as Bayesian inference are commonly used for parameter learning. Choosing the appropriate parameter search technique requires detailed domain knowledge and insight into the underlying system. Results: Using an agent-based model of the dynamics of acute inflammation, we demonstrate a novel parameter estimation algorithm by discovering the amount and schedule of doses of bacterial lipopolysaccharide that guarantee a set of observed clinical outcomes with high probability. We synthesized values of twenty-eight unknown parameters such that the parameterized model instantiated with these parameter values satisfies four specifications describing the dynamic behavior of the model. Conclusions: We have developed a new algorithmic technique for discovering parameters in complex stochastic models of biological systems given behavioral specifications written in a formal mathematical logic. Our algorithm uses Bayesian model checking, sequential hypothesis testing, and stochastic optimization to automatically synthesize parameters of probabilistic biological models.
KW - Acute inflammatory response
KW - Agent-based models
KW - Automated parameter synthesis
KW - Computational systems biology
KW - Parameter estimation
KW - Statistical model checking
UR - http://www.scopus.com/inward/record.url?scp=84961662095&partnerID=8YFLogxK
U2 - 10.1186/1471-2105-16-S17-S8
DO - 10.1186/1471-2105-16-S17-S8
M3 - Article
C2 - 26679759
AN - SCOPUS:84961662095
SN - 1471-2105
VL - 16
JO - BMC Bioinformatics
JF - BMC Bioinformatics
IS - 17
M1 - S8
ER -