Parameter estimation in stochastic biochemical reactions.
Gene regulatory, signal transduction and metabolic networks are major areas of interest in the newly emerging field of systems biology. In living cells, stochastic dynamics play an important role; however, the kinetic parameters of biochemical reactions necessary for modelling these processes are often not accessible directly through experiments. The problem of estimating stochastic reaction constants from molecule count data measured, with error, at discrete time points is considered. For modelling the system, a hidden Markov process is used, where the hidden states are the true molecule counts, and the transitions between those states correspond to reaction events following collisions of molecules. Two different algorithms are proposed for estimating the unknown model parameters. The first is an approximate maximum likelihood method that gives good estimates of the reaction parameters in systems with few possible reactions in each sampling interval. The second algorithm, treating the data as exact measurements, approximates the number of reactions in each sampling interval by solving a simple linear equation. Maximising the likelihood based on these approximations can provide good results, even in complex reaction systems.
Reinker
S
S
Department of Mathematics and Physics, FDM, University of Freiburg, Hermann-Herder-Str. 3, 79104 Freiburg, Germany. reinker@physik.uni-freiburg.de
Altman
R M
RM
Timmer
J
J
D000465:Algorithms; D001671:Biochemistry / Q000379:methods*; D003198:Computer Simulation; D008954:Models, Biological; D015233:Models, Statistical; D015398:Signal Transduction / Q000502:physiology*; D013269:Stochastic Processes; D014157:Transcription Factors / Q000378:metabolism*
D014157:Transcription Factors