Boada2016 - Incoherent type 1 feed-forward loop (I1-FFL)

  public model
Model Identifier
BIOMD0000000696
Short description
Boada2016 - Incoherent type 1 feed-forward loop (I1-FFL)
A synthetic-biology mathematical modelling framework that was constructed to provide guidelines for experimental implementation and parameter optimisation resulted in a biological device demonstrating desired behaviour.

This model is described in the article:

Boada Y, Reynoso-Meza G, Picó J, Vignoni A.
BMC Syst Biol 2016 Mar; 10: 27

Abstract:

Model based design plays a fundamental role in synthetic biology. Exploiting modularity, i.e. using biological parts and interconnecting them to build new and more complex biological circuits is one of the key issues. In this context, mathematical models have been used to generate predictions of the behavior of the designed device. Designers not only want the ability to predict the circuit behavior once all its components have been determined, but also to help on the design and selection of its biological parts, i.e. to provide guidelines for the experimental implementation. This is tantamount to obtaining proper values of the model parameters, for the circuit behavior results from the interplay between model structure and parameters tuning. However, determining crisp values for parameters of the involved parts is not a realistic approach. Uncertainty is ubiquitous to biology, and the characterization of biological parts is not exempt from it. Moreover, the desired dynamical behavior for the designed circuit usually results from a trade-off among several goals to be optimized.We propose the use of a multi-objective optimization tuning framework to get a model-based set of guidelines for the selection of the kinetic parameters required to build a biological device with desired behavior. The design criteria are encoded in the formulation of the objectives and optimization problem itself. As a result, on the one hand the designer obtains qualitative regions/intervals of values of the circuit parameters giving rise to the predefined circuit behavior; on the other hand, he obtains useful information for its guidance in the implementation process. These parameters are chosen so that they can effectively be tuned at the wet-lab, i.e. they are effective biological tuning knobs. To show the proposed approach, the methodology is applied to the design of a well known biological circuit: a genetic incoherent feed-forward circuit showing adaptive behavior.The proposed multi-objective optimization design framework is able to provide effective guidelines to tune biological parameters so as to achieve a desired circuit behavior. Moreover, it is easy to analyze the impact of the context on the synthetic device to be designed. That is, one can analyze how the presence of a downstream load influences the performance of the designed circuit, and take it into account.

This model is hosted on BioModels Database and identified by: BIOMD0000000696.

To cite BioModels Database, please use: Chelliah V et al. BioModels: ten-year anniversary. Nucl. Acids Res. 2015, 43(Database issue):D542-8.

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Format
SBML (L2V4)
Related Publication
  • Multi-objective optimization framework to obtain model-based guidelines for tuning biological synthetic devices: an adaptive network case.
  • Boada Y, Reynoso-Meza G, Picó J, Vignoni A
  • BMC systems biology , 3/ 2016 , Volume 10 , pages: 27 , PubMed ID: 26968941
  • Institut d'Automàtica i Informàtica Industrial, Universitat Politècnica de València, Valencia, Spain.
  • Model based design plays a fundamental role in synthetic biology. Exploiting modularity, i.e. using biological parts and interconnecting them to build new and more complex biological circuits is one of the key issues. In this context, mathematical models have been used to generate predictions of the behavior of the designed device. Designers not only want the ability to predict the circuit behavior once all its components have been determined, but also to help on the design and selection of its biological parts, i.e. to provide guidelines for the experimental implementation. This is tantamount to obtaining proper values of the model parameters, for the circuit behavior results from the interplay between model structure and parameters tuning. However, determining crisp values for parameters of the involved parts is not a realistic approach. Uncertainty is ubiquitous to biology, and the characterization of biological parts is not exempt from it. Moreover, the desired dynamical behavior for the designed circuit usually results from a trade-off among several goals to be optimized.We propose the use of a multi-objective optimization tuning framework to get a model-based set of guidelines for the selection of the kinetic parameters required to build a biological device with desired behavior. The design criteria are encoded in the formulation of the objectives and optimization problem itself. As a result, on the one hand the designer obtains qualitative regions/intervals of values of the circuit parameters giving rise to the predefined circuit behavior; on the other hand, he obtains useful information for its guidance in the implementation process. These parameters are chosen so that they can effectively be tuned at the wet-lab, i.e. they are effective biological tuning knobs. To show the proposed approach, the methodology is applied to the design of a well known biological circuit: a genetic incoherent feed-forward circuit showing adaptive behavior.The proposed multi-objective optimization design framework is able to provide effective guidelines to tune biological parameters so as to achieve a desired circuit behavior. Moreover, it is easy to analyze the impact of the context on the synthetic device to be designed. That is, one can analyze how the presence of a downstream load influences the performance of the designed circuit, and take it into account.
Contributors
Submitter of the first revision: Alejandro Vignoni
Submitter of this revision: administrator
Modellers: administrator, Alejandro Vignoni

Metadata information

is (2 statements)
BioModels Database MODEL1511290000
BioModels Database BIOMD0000000696

isDescribedBy (2 statements)
PubMed 26968941
PubMed 26968941

isVersionOf (3 statements)

Curation status
Curated

Tags

Connected external resources

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Model files

BIOMD0000000696_url.xml SBML L2V4 representation of Boada2016 - Incoherent type 1 feed-forward loop (I1-FFL) 131.42 KB Preview | Download

Additional files

BIOMD0000000696-biopax2.owl Auto-generated BioPAX (Level 2) 24.03 KB Preview | Download
BIOMD0000000696-biopax3.owl Auto-generated BioPAX (Level 3) 39.13 KB Preview | Download
BIOMD0000000696.m Auto-generated Octave file 11.97 KB Preview | Download
BIOMD0000000696.pdf Auto-generated PDF file 202.79 KB Preview | Download
BIOMD0000000696.png Auto-generated Reaction graph (PNG) 81.59 KB Preview | Download
BIOMD0000000696.sci Auto-generated Scilab file 154.00 Bytes Preview | Download
BIOMD0000000696.svg Auto-generated Reaction graph (SVG) 43.06 KB Preview | Download
BIOMD0000000696.vcml Auto-generated VCML file 893.00 Bytes Preview | Download
BIOMD0000000696.xpp Auto-generated XPP file 8.97 KB Preview | Download
BIOMD0000000696_urn.xml Auto-generated SBML file with URNs 131.16 KB Preview | Download
MODEL1511290000.cps Curated and annotated model COPASI file with plots to generate figures 5A and 5B. 135.20 KB Preview | Download
MODEL1511290000.sedml SED-ML file for figures 5A and 5B. A parameter scan was used to vary gamma_1 from 79 to 200 and k_mC*C_gC from 1 to 171. 4.74 KB Preview | Download

  • Model originally submitted by : Alejandro Vignoni
  • Submitted: Nov 29, 2015 11:01:46 PM
  • Last Modified: Apr 25, 2018 12:10:35 PM
Revisions
  • Version: 3 public model Download this version
    • Submitted on: Apr 25, 2018 12:10:35 PM
    • Submitted by: administrator
    • With comment: Notes updated using online editor.
  • Version: 2 public model Download this version
    • Submitted on: May 3, 2017 5:01:18 PM
    • Submitted by: Alejandro Vignoni
    • With comment: Current version of Boada2016 - Incoherent type 1 feed-forward loop (I1-FFL)
  • Version: 1 public model Download this version
    • Submitted on: Nov 29, 2015 11:01:46 PM
    • Submitted by: Alejandro Vignoni
    • With comment: Original import of Incoherent type 1 feed-forward loop (I1-FFL)

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
x2

protein
28336.8022705771 nmol
x3

Inducer
0.0 nmol
x4

urn:miriam:sbo:SBO%3A0000607
0.0 nmol
x6

protein
0.0 nmol
x7

mRNA
0.0 nmol
x1

mRNA
12.3973509933775 nmol
Reactions
Reactions Rate Parameters
x1 => x1 + x2 Cell*k_pA*x1 k_pA = 80.0
x9 => x9 + x3 k_d*x9 k_d = 0.06
x4 => Cell*k_3r*x4 k_3r = 1.0
x2 + x3 => Cell*k_2f*x2*x3 k_2f = 0.1
x6 => Cell*d_B*x6 d_B = 0.016
=> x7; x4, x6 Cell*k_mC_C_gC*(x4+Beta_1*gamma_4*x6+Beta_2*gamma_5*x4*x6)/(gamma_2+gamma_3*x4+gamma_4*x6+gamma_5*x4*x6) gamma_5 = 8.56; gamma_3 = 0.01; Beta_2 = 0.05; k_mC_C_gC = 1.0; gamma_4 = 1.15; gamma_2 = 0.2; Beta_1 = 0.05
x7 => x7 + x8 Cell*k_pC*x7 k_pC = 11.42
Curator's comment:
(added: 25 Apr 2018, 11:26:40, updated: 25 Apr 2018, 11:26:40)
A similar figure to figure 5B of the publication was reproduced. Parameter values from cluster 1 (table 4) were used. The curated figure shows simulation results from a parameter scan that used 2 intervals to change gamma_1 from 79 to 200 and k_mC*C_gC from 1 to 171. The sensitivity measure (J1) was also recorded and plotted as figure 5A. Low sensitivity scores (1e-1) correspond to the large peaks in protein c concentration (3e4) while higher sensitivity scores (1e1) correspond to low peaks (1e2) that are not visible in figure 5B. Using parameter values that result in lower sensitivity scores (1e-2) is likely to result in higher protein c peaks (5e4) as reported in the publication. Initial parameter values for k_mA*C_ga, k_pC, d_B, d_C, gamma_1, gamma_3, gamma_4 and gamma_5 were set to values found in the original encoded model. Parameter k_mC*C_gC was set to 1. The simulations were performed in COPASI 4.22 (Build 170) and the figures were generated in MATLAB R2014b.