92C45 Kinetics in biochemical problems (pharmacokinetics, enzyme kinetics, etc.) [See also 80A30]
Motivation. Modelling, parameter identification, and simulation play an important role in systems biology. Usually, the goal is to determine parameter values that minimise the difference between experimental measurement values and model predictions in a least-squares sense. Large-scale biological networks, however, often suffer from missing data for parameter identification. Thus, the least-squares problems are rank-deficient and solutions are not unique. Many common optimisation methods ignore this detail because they do not take into account the structure of the underlying inverse problem. These algorithms simply return a “solution” without additional information on identifiability or uniqueness. This can yield misleading results, especially if parameters are co-regulated and data are noisy.
Results. The Gauss-Newton method presented in this paper monitors the numerical rank of the Jacobian and converges locally, for the class of adequate problems, to a solution that is unique within the subspace of identifiable parameters. This method has been implemented in BioPARKIN, a software package that combines state-of-the-art numerical algorithms with compliance to system biology standards, most importantly SBML, and an accessible interface.
Availability. The software package BioPARKIN is available for download at http://bioparkin.zib.de .
Modelling, parameter identification, and simulation play an important rôle in Systems Biology. In recent years, various software packages have been established for scientific use in both licencing types, open source as well as commercial. Many of these codes are based on inefficient and mathematically outdated algorithms. By introducing the package BioPARKIN recently developed at ZIB, we want to improve this situation significantly. The development of the software BioPARKIN involves long standing mathematical ideas that, however, have not yet entered the field of Systems Biology, as well as new ideas and tools that are particularly important for the analysis of the dynamics of biological networks. BioPARKIN originates from the package PARKIN, written by P.Deuflhard and U.Nowak, that has been applied successfully for parameter identification in physical chemistry for many years.
The stochastic dynamics of a well-stirred mixture of molecular species
interacting through different biochemical reactions can be
accurately modelled by the chemical master equation (CME). Research in
the biology and scientific computing community has
concentrated mostly on the development of numerical techniques to
approximate the solution of the CME via many realizations of the associated
Markov jump process. The domain of exact and/or efficient methods for
directly solving the CME is still widely open, which is due to its
large dimension that grows exponentially with the number of molecular
species involved. In this article, we present an exact solution
formula of the CME for arbitrary initial conditions in the case where
the underlying system is governed by monomolecular reactions. The
solution can be expressed in terms of the convolution of multinomial
and product Poisson distributions with time-dependent parameters
evolving according to the traditional reaction-rate equations. This
very structured representation allows to deduce any property of the
solution. The model class includes many interesting examples and may
also be used as the starting point for the design of new numerical
methods for the CME of more complex reaction systems.