dynamic systems biology modeling and simulation distefano pdf

Dynamic systems biology modeling and simulation distefano pdf

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Observability and Structural Identifiability of Nonlinear Biological Systems

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Metrics details. Dynamic modelling is one of the cornerstones of systems biology. Many research efforts are currently being invested in the development and exploitation of large-scale kinetic models. The associated problems of parameter estimation model calibration and optimal experimental design are particularly challenging. The community has already developed many methods and software packages which aim to facilitate these tasks.

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Alejandro F. Observability is a modelling property that describes the possibility of inferring the internal state of a system from observations of its output. A related property, structural identifiability, refers to the theoretical possibility of determining the parameter values from the output. In fact, structural identifiability becomes a particular case of observability if the parameters are considered as constant state variables. It is possible to simultaneously analyse the observability and structural identifiability of a model using the conceptual tools of differential geometry.

Observability and Structural Identifiability of Nonlinear Biological Systems

The text has marvelous clarity, as do the mathematical demonstrations. All are synoptic, while simultaneously explaining the underlying, fine details. The useful organization is enhanced by superb graphics. Although the author has many technical capabilities, with both range and depth, below I'll give just one illustrative example of the excellent result. Major themes of modern computation and modeling, as applied to biology, include issues of nonlinearities, chaotic dynamics, emergent properties, and instabilities. For example, consider the problems attendant on complex dynamic systems with multiple scales of time and space so typical of living systems.

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A powerful way of gaining insight into biological systems is by creating a nonlinear differential equation model, which usually contains many unknown parameters. Such a model is called structurally identifiable if it is possible to determine the values of its parameters from measurements of the model outputs. Structural identifiability is a prerequisite for parameter estimation, and should be assessed before exploiting a model. However, this analysis is seldom performed due to the high computational cost involved in the necessary symbolic calculations, which quickly becomes prohibitive as the problem size increases. In this paper we show how to analyse the structural identifiability of a very general class of nonlinear models by extending methods originally developed for studying observability.

Hengl, C. Kreutz, J. Timmer, T. Motivation: Mathematical modelling of biological systems is becoming a standard approach to investigate complex dynamic, non-linear interaction mechanisms in cellular processes.

Dynamic Systems Biology Modeling and Simulation

In cell and molecular biology, metabolism is the only system that can be fully simulated at genome scale. Metabolic systems biology offers powerful abstraction tools to simulate all known metabolic reactions in a cell, therefore providing a snapshot that is close to its observable phenotype.

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During the last decades, high-throughput techniques allowed for the extraction of a huge amount of data from biological systems, unveiling more of their underling complexity. Biological systems encompass a wide range of space and time scales, functioning according to flexible hierarchies of mechanisms making an intertwined and dynamic interplay of regulations. This becomes particularly evident in processes such as ontogenesis, where regulative assets change according to process context and timing, making structural phenotype and architectural complexities emerge from a single cell, through local interactions. The information collected from biological systems are naturally organized according to the functional levels composing the system itself.

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3 comments

  • Alize A. 20.05.2021 at 07:01

    Ambiguities in some concepts and tools are clarified and others are rendered more accessible and practical.

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