4 research outputs found
Model Reduction Tools For Phenomenological Modeling of Input-Controlled Biological Circuits
We present a Python-based software package to automatically obtain phenomenological models of input-controlled synthetic biological circuits that guide the design using chemical reaction-level descriptive models. From the parts and mechanism description of a synthetic biological circuit, it is easy to obtain a chemical reaction model of the circuit under the assumptions of mass-action kinetics using various existing tools. However, using these models to guide design decisions during an experiment is difficult due to a large number of reaction rate parameters and species in the model. Hence, phenomenological models are often developed that describe the effective relationships among the circuit inputs, outputs, and only the key states and parameters. In this paper, we present an algorithm to obtain these phenomenological models in an automated manner using a Python package for circuits with inputs that control the desired outputs. This model reduction approach combines the common assumptions of time-scale separation, conservation laws, and species' abundance to obtain the reduced models that can be used for design of synthetic biological circuits. We consider an example of a simple gene expression circuit and another example of a layered genetic feedback control circuit to demonstrate the use of the model reduction procedure
Model Reduction Tools For Phenomenological Modeling of Input-Controlled Biological Circuits
We present a Python-based software package to automatically obtain phenomenological models of input-controlled synthetic biological circuits that guide the design using chemical reaction-level descriptive models. From the parts and mechanism description of a synthetic biological circuit, it is easy to obtain a chemical reaction model of the circuit under the assumptions of mass-action kinetics using various existing tools. However, using these models to guide design decisions during an experiment is difficult due to a large number of reaction rate parameters and species in the model. Hence, phenomenological models are often developed that describe the effective relationships among the circuit inputs, outputs, and only the key states and parameters. In this paper, we present an algorithm to obtain these phenomenological models in an automated manner using a Python package for circuits with inputs that control the desired outputs. This model reduction approach combines the common assumptions of time-scale separation, conservation laws, and species' abundance to obtain the reduced models that can be used for design of synthetic biological circuits. We consider an example of a simple gene expression circuit and another example of a layered genetic feedback control circuit to demonstrate the use of the model reduction procedure
The Quasi-Steady-State Approximations revisited: Timescales, small parameters, singularities, and normal forms in enzyme kinetic
In this work, we revisit the scaling analysis and commonly accepted
conditions for the validity of the standard, reverse and total
quasi-steady-state approximations through the lens of dimensional
Tikhonov-Fenichel parameters and their respective critical manifolds. By
combining Tikhonov-Fenichel parameters with scaling analysis and energy
methods, we derive improved upper bounds on the approximation error for the
standard, reverse and total quasi-steady-state approximations. Furthermore,
previous analyses suggest that the reverse quasi-steady-state approximation is
only valid when initial enzyme concentrations greatly exceed initial substrate
concentrations. However, our results indicate that this approximation can be
valid when initial enzyme and substrate concentrations are of equal magnitude.
Using energy methods, we find that the condition for the validity of the
reverse quasi-steady-state approximation is far less restrictive than was
previously assumed, and we derive a new "small" parameter that determines the
validity of this approximation. In doing so, we extend the established domain
of validity for the reverse quasi-steady-state approximation. Consequently,
this opens up the possibility of utilizing the reverse quasi-steady-state
approximation to model enzyme catalyzed reactions and estimate kinetic
parameters in enzymatic assays at much lower enzyme to substrate ratios than
was previously thought. Moreover, we show for the first time that the critical
manifold of the reverse quasi-steady-state approximation contains a singular
point where normal hyperbolicity is lost. Associated with this singularity is a
transcritical bifurcation, and the corresponding normal form of this
bifurcation is recovered through scaling analysis.Comment: 50 pages, 10 figures, 1 tabl