Finite state projection based bounds to compare chemical master equation models using single-cell data

Emerging techniques now allow for precise quantification of distributions of biological molecules in single cells. These rapidly advancing experimental methods have created a need for more rigorous and efficient modeling tools. Here, we derive new bounds on the likelihood that observations of single...

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Bibliographic Details
Published in:	The Journal of chemical physics 2016-08, Vol.145 (7), p.074101-074101
Main Authors:	Fox, Zachary, Neuert, Gregor, Munsky, Brian
Format:	Article
Language:	eng
Subjects:	Biophysical Phenomena Cells - chemistry Computer simulation EQUATIONS EXPERIMENTAL DATA Forecasting INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL CHEMISTRY Lower bounds Models, Chemical Organic chemistry Parameter identification Physics SIMULATION Single-Cell Analysis Stochastic models Stochastic Processes Yeast
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Summary:	Emerging techniques now allow for precise quantification of distributions of biological molecules in single cells. These rapidly advancing experimental methods have created a need for more rigorous and efficient modeling tools. Here, we derive new bounds on the likelihood that observations of single-cell, single-molecule responses come from a discrete stochastic model, posed in the form of the chemical master equation. These strict upper and lower bounds are based on a finite state projection approach, and they converge monotonically to the exact likelihood value. These bounds allow one to discriminate rigorously between models and with a minimum level of computational effort. In practice, these bounds can be incorporated into stochastic model identification and parameter inference routines, which improve the accuracy and efficiency of endeavors to analyze and predict single-cell behavior. We demonstrate the applicability of our approach using simulated data for three example models as well as for experimental measurements of a time-varying stochastic transcriptional response in yeast.
ISSN:	0021-9606 1089-7690