Abstract
System theory has its roots in mathematical formalisms developed by mathematicians and physicians, such as Leibniz, Euler and Newton, and applied by congenial ecologists and biologists such as Lotka and Bertalanffy. In these approaches the dynamical system – may it be either single organisms or populations of organisms in their ecosystems – is defined and formally translated into an interaction matrix and first order ordinary differential equations (ODE) which are then solved. This provides the background for the quantitative analysis of any linear to non-linear system. In his inspiring article “ can a biologist fix a radio?” Lazebnik made the differences very clear between a “guilt-by association” hypothesis of a modern biologist versus a Signal-Input-Output (SIO) model of an electrical engineer. The drawback of this “Gedankenexperiment” is that two different approaches are compared – a forward approach in case of the SIO model by an engineer and an inverse or reverse approach by the biologist or ecologist. The point is that biological and ecological systems are much too complex to estimate the deterministic input signals that generate a probability distribution. Thus, a combination of reverse data-driven modelling with stochastic simulation is a key process to understand the control of a biological or ecological system. The challenge of the next decades of systems biology is to link these approaches more systematically. Over the last years we and others have developed such an hybrid modelling approach based on the stochastic Lyapunov matrix equation for the analysis of genome-scale molecular data which links forward and reverse strategies such as the genome-scale based metabolic reconstruction of an organism and the calculation of dynamics around a quasi steady state using statistical features of large-scale PANOMICS data. PANOMICS combines all molecular and phenotypical levels of an organism from the genome, transcriptome, proteome, metabolome to morphology and physiology to unambiguously define the genotype-phenotype-relationship. This system-theoretical formalism establishes the generic analysis of the genotype-environment-phenotype-relationship to finally result in predictability of organismal function.
Highlights
Specialty section: This article was submitted to Systems Biology, a section of the journal Frontiers in Applied Mathematics and Statistics
We have developed a hybrid modeling approach based on the stochastic Lyapunov matrix equation for the analysis of genome-scale molecular data
This workflow connects forward and inverse strategies such as the genome-scale-based metabolic reconstruction of an organism and the calculation of dynamics around a quasi-steady state using statistical features of large-scale multiomics data. This workflow is linked to physiology and phenotype to unambiguously define the genotype–environment–phenotype relationship. This system-theoretical formalism establishes the generic analysis of the genotype–environment–phenotype relationship to result in predictability of organismal function in the environmental context
Summary
The pioneering work of Bertalanffy and others still provides the basic principles necessary to analyze any complex biological and ecological system. For an n-dimensional system the Jacobian matrix reads: The solution to these systems is again given by the matrix eigenvalue/eigenvector Equation (10) [52, 54, 55]: Once we derive the Jacobian of a system of coupled first-order differential equations, we can calculate eigenvalues and vectors, which describe stability and system properties close to a steady state or quasi equilibrium. This equation is used in the forward approach for deriving an unknown covariance matrix Cov by knowing the systems equations resulting in the Jacobian J—as described above—and the diffusion matrix Q representing the fluctuation or perturbations of the system around a steady state or critical point [62, 67] This equation is central in the theory of stochastic processes [66, 68] and has been solved by various approaches [69,70,71].
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