comp


SBML Hierarchical Model Composition

SBML models can be composed together to create larger models using the comp extension. This example shows how to combine three genetic circuits in Antimony. The example consists of:

  1. A bistable switch which contains two genes, with one driven by the external input x.
  2. A feed forward forward loop which filters the signal.
  3. A simple oscillator (the ring oscillator).

These models are combined into a single larger model by wiring the inputs and outputs.


In [1]:
//------------------------------------------
//Bistable Switch
//Two genes down-regulate one another. Hill coefficient = 2
//input x can be used to upregulate one of the genes
//------------------------------------------
model bistable(s1, s2)
   gene g1, g2;
   species s1, s2;
   g1: -> s1; k1/(1 + k2*s2^2) //gene 1 makes protein s1
   s1 -> ; k0*s1                       //protein 1 degrades
   g2: -> s2; k3/(1 + k4*s1^2)         //gene 2 makes protein s2
   s2 -> ; k0*s2                       //protein s2 degrades

   k0 = 0.1         //parameters in the model
   k1 = 1
   k2 = 1
   k3 = 1
   k4 = 1
end

//------------------------------------------
//Feed Forward Network (Coherent Type 1)
//The FFN is meant to reduce noise -- the signal x has to last long
//enough if x is short lived, then g2 does not receive the signal
//------------------------------------------
model ffn(x, s2)
   gene g1, g2;         
   species x, s1, s2;
   
   g1: -> s1; x/(1 + x)         //gene 1 makes protein s1
   s1 -> ; k1*s1                //s1 degrades
   g2: -> s2; x*s1/(1 + x + s1) //gene 2 makes protein s2
   s2 -> ; k2*s2		       //s2 degrades

   k0 = 0.1
   k1 = 0.1
   k2 = 0.1*k0
end

//------------------------------------------
//A ring oscillator (similar to the repressilator)
//The input x can be used to disturb the oscillator
//------------------------------------------
model ringoscil(x)
    gene g1, g2, g3
    species s1, s2, s3, x

    g1: -> s1; k1/(1 + x + s3^2)
    s1 -> ; k0*s1
    g2: -> s2; k1/(1 + s1^3)
    s2 -> ; k0*s2
    g3: -> s3; k1/(1 + s2^3)
    s3 -> ; k0*s3

    k1 = 2
    k0 = 0.1
end

//------------------------------------------
//The combined Model
// The bistable switch has two proteins - y and z.
// z also interacts with the oscillator to disrupt it.
// The FFN can be used to change the state of the bistable switch
//------------------------------------------
// EFFECT: the duration of signal x determines whether 
// the oscillator turns on.
//------------------------------------------
model combined_model(x)
    A: bistable(y,z)
    B: ringoscil(z)
    C: ffn(x,y)
end

model main_comb()
    C: combined_model(x)
    x = 10
    x -> ; k0*x //The signal degrades over time, giving us a pulse.
    k0 = 0.1
end

# run through oscillating and non-oscillating cases
model_osc = model "main_comb" with k0 = 0.001
model_noosc = model "main_comb" with k0 = 100

sim1 = simulate uniform(0, 1000, 250)

task_osc = run sim1 on model_osc
task_noosc = run sim1 on model_noosc

# to visualize the dynamics, the important variables are:
# - 1. Time
# - 2. The input x
# - 3. The ffn output y
# - 4. One of the ring osc variables (s1)
plot "Oscillating Case (k0 = 0.001)" task_osc.time vs task_osc.x, task_osc.C_y, task_osc.C_B_s1
plot "Nonoscillating Case (k0 = 100)" task_noosc.time vs task_noosc.x, task_noosc.C_y, task_noosc.C_B_s1