"""
This module contains a number of tests that can be used to verify that
the behavior of the MOMP-only sub-models based on [Albeck2008]_
and re-written in PySB match the original publication. To verify that
the PySB version of the models match the original models (which were written
in MATLAB), timecourse data was generated in MATLAB using the original MATLAB
code, and saved in tab-separated data files (`albeck_11{b-f}.tsv`). The PySB
models are then run using the same input and the output is verified to match
the original data (within integration tolerances).
This model verification procedure is written as a series of unit tests, one
for each sub-model, using the built-in Python package unittest.
To run the tests, simply execute this file at the command line, i.e.::
python test_albeck_models.py
and all tests should pass.
"""
import unittest
from pysb import *
from pysb.bng import generate_equations
from pysb.integrate import odesolve
from earm.mito import albeck_11b
from earm.mito import albeck_11c
from earm.mito import albeck_11d
from earm.mito import albeck_11e
from earm.mito import albeck_11f
from matplotlib.pyplot import figure, ion, plot, legend
import numpy as np
import os.path
# The default integration tolerance in pysb.integrate
rtol = 1e-6
[docs]def add_caspase8(model):
"""Add the reaction C8 + Bid <-> C8:Bid -> C8 + tBid.
All of the MOMP sub-models in this model repository have been written
to have tBid as their upstream "interface," and Smac/Cytochrome C release
as their downstream "interface." However, in the original publication
[Albeck2008]_, the authors incorporated the additional upstream
step of Bid cleavage by caspase 8 into all of the sub-models that they
explored.
Therefore, to match the output of the PySB models in this repository to
the output produced by the original MATLAB models, it is necessary to add
the upstream caspase-8:Bid reactions.
This function takes a model object and adds the necessary elements:
- Caspase-8 Monomer
- Caspase-8 initial condition
- Caspase-8/Bid cleavage reaction and associated parameters
In addition, since in the original publication the plotted figures
considered Smac release kinetics in the absence of Cytochrome C release,
this function sets the Cytochrome C initial condition to 0 (this prevents
Cytochrome C from competing with Smac for pore transport, which affects
the observed Smac release kinetics slightly).
"""
# If not already added, add upstream caspase reactions to model
if model.monomers.get('C8') is None:
Bid = model.monomers.get('Bid')
# Add caspase 8
C8 = Monomer('C8', ['state', 'bf'], {'state': ['pro', 'A']},
_export=False)
model.add_component(C8)
# Add caspase 8 initial condition (with placeholder value 1)
C8_0 = Parameter('C8_0', 1, _export=False)
model.add_component(C8_0)
model.initial(C8(state='A', bf=None), C8_0)
# Add rules C8 + Bid <-> C8:Bid -> Bid + C8*
kf = Parameter('bind_C8A_BidU_to_C8ABidU_kf', 1e-7, _export=False)
kr = Parameter('bind_C8A_BidU_to_C8ABidU_kr', 1e-3, _export=False)
kc = Parameter('catalyze_C8ABidU_to_C8A_BidT_kc', 1, _export=False)
model.add_component(kf)
model.add_component(kr)
model.add_component(kc)
rb = Rule('bind_C8A_BidU_to_C8ABidU',
C8(state='A', bf=None) + Bid(state='U', bf=None) <>
C8(state='A', bf=1) % Bid(state='U', bf=1),
kf, kr, _export=False)
rc = Rule('catalyze_C8ABidU_to_C8A_BidT',
C8(state='A', bf=1) % Bid(state='U', bf=1) >>
C8(state='A', bf=None) + Bid(state='T', bf=None),
kc, _export=False)
model.add_component(rb)
model.add_component(rc)
# Set CytoC to 0 so transport is only of Smac
model.parameters['CytoC_0'].value = 0
## TESTS ===============================================================
[docs]class TestAlbeck11b(unittest.TestCase):
"""Test the PySB model based on the topology shown in Figure 11b."""
def setUp(self):
self.model = albeck_11b.model
add_caspase8(self.model)
[docs]class TestAlbeck11c(unittest.TestCase):
"""Test the PySB model based on the topology shown in Figure 11c."""
def setUp(self):
self.model = albeck_11c.model
add_caspase8(self.model)
[docs]class TestAlbeck11d(unittest.TestCase):
"""Test the PySB model based on the topology shown in Figure 11d."""
def setUp(self):
self.model = albeck_11d.model
add_caspase8(self.model)
[docs]class TestAlbeck11e(unittest.TestCase):
"""Test the PySB model based on the topology shown in Figure 11e."""
def setUp(self):
self.model = albeck_11e.model
add_caspase8(self.model)
[docs]class TestAlbeck11f(unittest.TestCase):
"""Test the PySB model based on the topology shown in Figure 11f."""
def setUp(self):
self.model = albeck_11f.model
add_caspase8(self.model)
if __name__ == '__main__':
unittest.main()