def test_stop_if():
Model()
Monomer('A')
Rule('A_synth', None >> A(), Parameter('k', 1))
Observable('Atot', A())
Expression('exp_const', k + 1)
Expression('exp_dyn', Atot + 1)
sim = BngSimulator(model, verbose=5)
tspan = np.linspace(0, 100, 101)
x = sim.run(tspan, stop_if='Atot>9', seed=_BNG_SEED)
# All except the last Atot value should be <=9
assert all(x.observables['Atot'][:-1] <= 9)
assert x.observables['Atot'][-1] > 9
# Starting with Atot > 9 should terminate simulation immediately
y = sim.run(tspan, initials=x.species[-1], stop_if='Atot>9')
assert len(y.observables) == 1
def test_integrate_with_expression():
"""Ensure a model with Expressions simulates."""
Monomer('s1')
Monomer('s9')
Monomer('s16')
Monomer('s20')
# Parameters should be able to contain s(\d+) without error
Parameter('ks0', 2e-5)
Parameter('ka20', 1e5)
Initial(s9(), Parameter('s9_0', 10000))
Observable('s1_obs', s1())
Observable('s9_obs', s9())
Observable('s16_obs', s16())
Observable('s20_obs', s20())
Expression('keff', (ks0 * ka20) / (ka20 + s9_obs))
Rule('R1', None >> s16(), ks0)
Rule('R2', None >> s20(), ks0)
Rule('R3', s16() + s20() >> s16() + s1(), keff)
time = np.linspace(0, 40)
x = odesolve(model, time)
def test_integrate_with_expression():
"""Ensure a model with Expressions simulates."""
Monomer('s1')
Monomer('s9')
Monomer('s16')
Monomer('s20')
# Parameters should be able to contain s(\d+) without error
Parameter('ks0', 2e-5)
Parameter('ka20', 1e5)
Initial(s9(), Parameter('s9_0', 10000))
Observable('s1_obs', s1())
Observable('s9_obs', s9())
Observable('s16_obs', s16())
Observable('s20_obs', s20())
Expression('keff', (ks0 * ka20) / (ka20 + s9_obs))
Rule('R1', None >> s16(), ks0)
Rule('R2', None >> s20(), ks0)
Rule('R3', s16() + s20() >> s16() + s1(), keff)
time = np.linspace(0, 40)
sim = ScipyOdeSimulator(model, tspan=time)
simres = sim.run()
keff_vals = simres.expressions['keff']
assert len(keff_vals) == len(time)
assert np.allclose(keff_vals, 1.8181818181818182e-05)
def test_integrate_with_expression():
"""Ensure a model with Expressions simulates."""
Monomer('s1')
Monomer('s9')
Monomer('s16')
Monomer('s20')
# Parameters should be able to contain s(\d+) without error
Parameter('ks0', 2e-5)
Parameter('ka20', 1e5)
Initial(s9(), Parameter('s9_0', 10000))
Observable('s1_obs', s1())
Observable('s9_obs', s9())
Observable('s16_obs', s16())
Observable('s20_obs', s20())
Expression('keff', (ks0 * ka20) / (ka20 + s9_obs))
Rule('R1', None >> s16(), ks0)
Rule('R2', None >> s20(), ks0)
Rule('R3', s16() + s20() >> s16() + s1(), keff)
time = np.linspace(0, 40)
solver = Solver(model, time)
solver.run()
assert solver.yexpr_view.shape == (len(time),
len(model.expressions_dynamic()))
assert solver.yobs_view.shape == (len(time), len(model.observables))
def test_unicode_exprname_nonascii():
"""Ensure non-ascii unicode expression names error in python 2."""
t = np.linspace(0, 100)
rob_copy = copy.deepcopy(robertson.model)
ab = rob_copy.observables['A_total'] + rob_copy.observables['B_total']
expr = Expression(u'A_plus_B\u1234', ab, _export=False)
rob_copy.add_component(expr)
sim = ScipyOdeSimulator(rob_copy)
simres = sim.run(tspan=t)
def add_gf_bolus(model, name: str, created_monomers: List[str]):
bolus = Monomer(f'{name}_ext')
Initial(bolus(), Parameter(f'{name}_0', 0.0), fixed=True)
for created_monomer in created_monomers:
koff = Parameter(f'{name}_{created_monomer}_koff', 0.1)
kd = Parameter(f'{name}_{created_monomer}_kd', 1.0)
kon = Expression(f'{name}_{created_monomer}_kon', kd * koff)
Rule(f'{name}_ext_to_{created_monomer}',
bolus() | model.monomers[created_monomer](inh=None), kon, koff)
def add_abundance_observables(model):
"""
Adds an observable that tracks the normalized absolute abundance of a
protein
"""
for monomer in model.monomers:
obs = Observable(f'total_{monomer.name}', monomer())
scale = Parameter(f't{monomer.name}_scale', 1.0)
offset = Parameter(f't{monomer.name}_offset', 1.0)
Expression(f't{monomer.name}_obs', sp.log(scale * (obs + offset)))
def test_unicode_exprname_ascii():
"""Ensure ascii-convetible unicode expression names are handled."""
t = np.linspace(0, 100)
rob_copy = copy.deepcopy(robertson.model)
ab = rob_copy.observables['A_total'] + rob_copy.observables['B_total']
expr = Expression(u'A_plus_B', ab, _export=False)
rob_copy.add_component(expr)
sim = ScipyOdeSimulator(rob_copy)
simres = sim.run(tspan=t)
simres.all
simres.dataframe
def add_phospho_observables(model):
"""
Adds an observable that tracks the normalized absolute abundance of a
phosphorylated site
"""
for monomer in model.monomers:
for site in monomer.site_states:
if re.match(r'[YTS][0-9]+$', site):
obs = Observable(f'p{monomer.name}_{site}',
monomer(**{site: 'p'}))
scale = Parameter(f'p{monomer.name}_{site}_scale', 1.0)
offset = Parameter(f'p{monomer.name}_{site}_offset', 1.0)
Expression(f'p{monomer.name}_{site}_obs',
sp.log(scale * (obs + offset)))
def add_inhibitor(model: Model, name: str, targets: List[str]):
inh = Parameter(f'{name}_0', 0.0)
kd = Parameter(f'{name}_kd', 0.0)
affinities = {
target:
Expression(f'inh_{target}',
Observable(f'target_{target}', model.monomers[target]) / kd)
for target in targets
}
for expr in model.expressions:
if expr.name.startswith('inh_'):
continue
target = next(
(next(mp.monomer.name for cp in s.reaction_pattern.complex_patterns
for mp in cp.monomer_patterns if mp.monomer.name in targets)
for s in expr.expr.free_symbols
if isinstance(s, Observable) and any(
mp.monomer.name in targets
for cp in s.reaction_pattern.complex_patterns
for mp in cp.monomer_patterns)), None)
if target is None:
continue
expr.expr *= 1 / (1 + inh * affinities[target])
def add_activation(model: Model,
m_name: str,
site: str,
activation_type: str,
activators: Optional[Iterable[str]] = None,
deactivators: Optional[Iterable[str]] = None):
"""
Adds activation/deactivation rules to a specific site
:param model:
model to which the rules will be added
:param m_name:
monomer name
:param site:
site name
:param activation_type:
type of activation, valid values are
{`phosphorylation`, `nucleotide_exchange`, `tf_activation`}
:param activators:
molecular species that activate the respective site, format
according to modulator format in :py:func:`add_or_get_modulator_obs`
:param deactivators:
molecular species that deactivate the respective site, format
according to modulator format in :py:func:`add_or_get_modulator_obs`
"""
if activators is None:
activators = []
if deactivators is None:
deactivators = []
if m_name not in model.monomers.keys():
raise ValueError(f'{m_name} is not a monomer in the model.')
mono = model.monomers[m_name]
if activation_type == 'phosphorylation':
valid_states = ['u', 'p']
elif activation_type == 'nucleotide_exchange':
valid_states = ['gdp', 'gtp']
elif activation_type == 'tf_activation':
valid_states = ['active', 'inactive']
else:
raise ValueError(f'Invalid activation type {activation_type}.')
sites = [site for site in site.split('_')]
for site in sites:
if site not in mono.site_states \
or len(mono.site_states[site]) != len(valid_states) \
or any(state not in mono.site_states[site]
for state in valid_states):
raise ValueError(f'{site} is not a valid target for '
f'{activation_type}.')
if activation_type == 'phosphorylation':
forward = 'phosphorylation'
backward = 'dephosphorylation'
fstate = {site: 'u' for site in sites}
rstate = {site: 'p' for site in sites}
elif activation_type == 'nucleotide_exchange':
forward = 'gtp_exchange'
backward = 'gdp_exchange'
fstate = {site: 'gdp' for site in sites}
rstate = {site: 'gtp' for site in sites}
else:
raise ValueError(f'Invalid activation type {activation_type}.')
for label, educts, products, modulators in zip(
[forward, backward],
[mono(**fstate), mono(**rstate)],
[mono(**rstate), mono(**fstate)],
[activators, deactivators],
):
for modulator in modulators:
kcat = Parameter(f'{m_name}_{label}_{site}_{modulator}_kcat', 1.0)
rate_expr = kcat * add_or_get_modulator_obs(model, modulator)
# if label == forward:
rate_expr *= get_autoencoder_modulator(kcat)
rate = Expression(f'{m_name}_{label}_{site}_{modulator}_rate',
rate_expr)
Rule(F'{m_name}_{label}_{site}_{modulator}', educts >> products,
rate)
# Rulebender to PySB. This is just a model file - must be run from a run file
from pysb import Model, Parameter, Expression, Initial, Monomer, Observable, Rule, WILD
# Begin Model
Model()
# =============================================================================
# # Parameters
# =============================================================================
Parameter('NA', 6.022E23) # Avogadro's number (molecues/mol)
Parameter('PI', 3.142) # no unit
Parameter('rad_cell', 30E-6) # radius of cell in m approx 30 micron
Parameter('cell_thickness', 8E-6) # height, m
Parameter('cell_dens', 1E5) # density of cells , /L
Parameter('width_PM', 1E-6) # effective width of membrane , m
Expression('volEC', 1 / cell_dens) # vol. extracellular space , L
Expression(
'volPM', 2 * rad_cell**2 +
rad_cell * cell_thickness * 4) # virtual vol. of plasma membrane , L
Expression('volCP', cell_thickness * rad_cell**2) # vol. of cytoplasm , L
Parameter('IFN', 1E-9) # initial concentration in Molar
Expression('I', IFN * volEC *
NA) # number of copies per cell (~ 6.022e8 copies per cell)
Expression('Ia', I)
#Expression('Ib', I)
#Parameter('r', 0) # Receptor assymmetry
#Parameter('R', 0) #
Parameter('R1', 2000) #(2000/7.2e-15)*volCP#(8000/2.76e-9)*volPM#R -r#
Parameter(
'R2', 2000
Parameter('MAP2K2_phosphorylation_S226_BRAF__S445_p_kcat', 1.0)
Parameter('INPUT_MAP2K2_phosphorylation_S226_BRAF__S445_p_kcat', 0.0)
Parameter('MAPK1_phosphorylation_Y187_MAP2K1__S218_p__S222_p_kcat', 1.0)
Parameter('INPUT_MAPK1_phosphorylation_Y187_MAP2K1__S218_p__S222_p_kcat', 0.0)
Parameter('MAPK1_phosphorylation_Y187_MAP2K2__S222_p__S226_p_kcat', 1.0)
Parameter('INPUT_MAPK1_phosphorylation_Y187_MAP2K2__S222_p__S226_p_kcat', 0.0)
Parameter('MAPK3_phosphorylation_Y204_MAP2K1__S218_p__S222_p_kcat', 1.0)
Parameter('INPUT_MAPK3_phosphorylation_Y204_MAP2K1__S218_p__S222_p_kcat', 0.0)
Parameter('MAPK3_phosphorylation_Y204_MAP2K2__S222_p__S226_p_kcat', 1.0)
Parameter('INPUT_MAPK3_phosphorylation_Y204_MAP2K2__S222_p__S226_p_kcat', 0.0)
Parameter('iEGFR_0', 0.0)
Parameter('iEGFR_kd', 0.0)
Parameter('iMEK_0', 0.0)
Parameter('iMEK_kd', 0.0)
Expression('EGF_EGF_kon', EGF_EGF_kd * EGF_EGF_koff)
Expression(
'EGFR_dephosphorylation_Y1173_base_rate',
EGFR_dephosphorylation_Y1173_base_kcat *
INPUT_EGFR_dephosphorylation_Y1173_base_kcat)
Expression(
'ERBB2_dephosphorylation_Y1248_base_rate',
ERBB2_dephosphorylation_Y1248_base_kcat *
INPUT_ERBB2_dephosphorylation_Y1248_base_kcat)
Expression(
'RAF1_dephosphorylation_S338_base_rate',
INPUT_RAF1_dephosphorylation_S338_base_kcat *
RAF1_dephosphorylation_S338_base_kcat)
Expression(
'BRAF_dephosphorylation_S445_base_rate',
BRAF_dephosphorylation_S445_base_kcat *
Monomer('R', ['r', 'i']) #RAF
Monomer('I', ['r']) #RAF inhibitor
#Kinetic parameters, koff /s/M, kon /s
Parameter('koff_RR', 10**-1)
Parameter('kon_RR', 10**-2)
Parameter('koff_RI', 10**-1)
Parameter('kon_RI', 10)
#Thermodynamic factors, no units
Parameter('f', 1)
Parameter('g', 1)
#Rate distribution parameter, no units
Parameter('phi', 0.5)
#Standard free energy of formation, kJ/mol.
Expression('Gf_RR', getGfRT(kon_RR, koff_RR))
Expression('Gf_RI', getGfRT(kon_RI, koff_RI))
Expression('f_Gf', getTGfRT(f))
Expression('g_Gf', getTGfRT(g))
#Baseline activation energy, kJ/mol.
Expression('Ea0_RR', getEa0RT(kon_RR, koff_RR, phi))
Expression('Ea0_RI', getEa0RT(kon_RI, koff_RI, phi))
#RAF dimerization
EnergyPattern('ep_RR', R(r=1) % R(r=1), Gf_RR)
Rule('RR_binding',
R(r=None) + R(r=None) | R(r=1) % R(r=1),
phi,
Ea0_RR,
energy=True)
def add_monomer_synth_deg(m_name: str,
psites: Optional[Iterable[str]] = None,
nsites: Optional[Iterable[str]] = None,
asites: Optional[Iterable[str]] = None,
asite_states: Optional[Iterable[str]] = None):
"""
Adds the respective monomer plus synthesis rules and basal
activation/deactivation rules for all activateable sites
:param m_name:
monomer name
:param psites:
phospho sites
:param nsites:
nucleotide sites
:param asites:
other activity encoding sites
"""
if psites is None:
psites = []
else:
psites = list({site for psite in psites for site in psite.split('_')})
if nsites is None:
nsites = []
if asites is None:
asites = []
if asite_states is None:
asite_states = ['inactive', 'active']
sites = psites + nsites + asites + ['inh']
m = Monomer(m_name,
sites=sites,
site_states={
site: ['u', 'p'] if site in psites else
['gdp', 'gtp'] if site in nsites else asite_states
for site in sites if site in psites + nsites + asites
})
#kdeg = Parameter(f'{m_name}_degradation_kdeg', 1.0)
t = Parameter(f'{m_name}_eq', 100.0)
#ksyn = Expression(f'{m_name}_synthesis_ksyn', t*kdeg)
#syn_rate = Expression(f'{m_name}_synthesis_rate',
# ksyn * get_autoencoder_modulator(t))
syn_prod = m(
**{
site: 'u' if site in psites else 'gdp' if site in
nsites else None if site is 'inh' else asite_states[0]
for site in sites
})
#Rule(f'synthesis_{m_name}', None >> syn_prod, syn_rate)
#deg_rate = Expression(f'{m_name}_degradation_rate', kdeg)
#Rule(f'degradation_{m_name}', m() >> None, deg_rate)
#t_ss = Expression(f'{m_name}_ss', syn_rate/deg_rate)
Initial(syn_prod, t)
# basal activation
for sites, labels, fstate, rstate in zip(
[psites, nsites, asites], [('phosphorylation', 'dephosphorylation'),
('gtp_exchange', 'gdp_exchange'),
('activation', 'deactivation')],
['p', 'gtp', asite_states[1]], ['u', 'gdp', asite_states[0]]):
for site in sites:
kcats = [
Parameter(f'{m_name}_{label}_{site}_base_kcat', 1.0)
for label in labels[1:]
]
rates = [
Expression(f'{m_name}_{label}_{site}_base_rate',
kcat * get_autoencoder_modulator(kcat))
for kcat, label in zip(kcats, labels[1:])
]
#Rule(F'{m_name}_{site}_base',
# m(**{site: rstate}) | m(**{site: fstate}), *rates)
Rule(F'{m_name}_{site}_base',
m(**{site: fstate}) >> m(**{site: rstate}), *rates)
return m
Parameter('MAP2K1_phosphorylation_S222_BRAF__S447_p_kcat', 1.0)
Parameter('INPUT_MAP2K1_phosphorylation_S222_BRAF__S447_p_kcat', 0.0)
Parameter('MAP2K2_phosphorylation_S226_RAF1__S338_p_kcat', 1.0)
Parameter('INPUT_MAP2K2_phosphorylation_S226_RAF1__S338_p_kcat', 0.0)
Parameter('MAP2K2_phosphorylation_S226_BRAF__S447_p_kcat', 1.0)
Parameter('INPUT_MAP2K2_phosphorylation_S226_BRAF__S447_p_kcat', 0.0)
Parameter('MAPK1_phosphorylation_Y187_MAP2K1__S218_p__S222_p_kcat', 1.0)
Parameter('INPUT_MAPK1_phosphorylation_Y187_MAP2K1__S218_p__S222_p_kcat', 0.0)
Parameter('MAPK1_phosphorylation_Y187_MAP2K2__S222_p__S226_p_kcat', 1.0)
Parameter('INPUT_MAPK1_phosphorylation_Y187_MAP2K2__S222_p__S226_p_kcat', 0.0)
Parameter('MAPK3_phosphorylation_Y204_MAP2K1__S218_p__S222_p_kcat', 1.0)
Parameter('INPUT_MAPK3_phosphorylation_Y204_MAP2K1__S218_p__S222_p_kcat', 0.0)
Parameter('MAPK3_phosphorylation_Y204_MAP2K2__S222_p__S226_p_kcat', 1.0)
Parameter('INPUT_MAPK3_phosphorylation_Y204_MAP2K2__S222_p__S226_p_kcat', 0.0)
Expression('FLT3_dephosphorylation_Y843_base_rate', FLT3_dephosphorylation_Y843_base_kcat*INPUT_FLT3_dephosphorylation_Y843_base_kcat)
Expression('HRAS_gdp_exchange_N_base_rate', HRAS_gdp_exchange_N_base_kcat*INPUT_HRAS_gdp_exchange_N_base_kcat)
Expression('KRAS_gdp_exchange_N_base_rate', INPUT_KRAS_gdp_exchange_N_base_kcat*KRAS_gdp_exchange_N_base_kcat)
Expression('NRAS_gdp_exchange_N_base_rate', INPUT_NRAS_gdp_exchange_N_base_kcat*NRAS_gdp_exchange_N_base_kcat)
Expression('RAF1_dephosphorylation_S338_base_rate', INPUT_RAF1_dephosphorylation_S338_base_kcat*RAF1_dephosphorylation_S338_base_kcat)
Expression('BRAF_dephosphorylation_S447_base_rate', BRAF_dephosphorylation_S447_base_kcat*INPUT_BRAF_dephosphorylation_S447_base_kcat)
Expression('MAP2K1_dephosphorylation_S222_base_rate', INPUT_MAP2K1_dephosphorylation_S222_base_kcat*MAP2K1_dephosphorylation_S222_base_kcat)
Expression('MAP2K1_dephosphorylation_S218_base_rate', INPUT_MAP2K1_dephosphorylation_S218_base_kcat*MAP2K1_dephosphorylation_S218_base_kcat)
Expression('MAP2K2_dephosphorylation_S222_base_rate', INPUT_MAP2K2_dephosphorylation_S222_base_kcat*MAP2K2_dephosphorylation_S222_base_kcat)
Expression('MAP2K2_dephosphorylation_S226_base_rate', INPUT_MAP2K2_dephosphorylation_S226_base_kcat*MAP2K2_dephosphorylation_S226_base_kcat)
Expression('MAPK1_dephosphorylation_T185_base_rate', INPUT_MAPK1_dephosphorylation_T185_base_kcat*MAPK1_dephosphorylation_T185_base_kcat)
Expression('MAPK1_dephosphorylation_Y187_base_rate', INPUT_MAPK1_dephosphorylation_Y187_base_kcat*MAPK1_dephosphorylation_Y187_base_kcat)
Expression('MAPK3_dephosphorylation_Y204_base_rate', INPUT_MAPK3_dephosphorylation_Y204_base_kcat*MAPK3_dephosphorylation_Y204_base_kcat)
Expression('MAPK3_dephosphorylation_T202_base_rate', INPUT_MAPK3_dephosphorylation_T202_base_kcat*MAPK3_dephosphorylation_T202_base_kcat)
Observable('FL_obs', FL(inh=None))
Parameter('EGF_eq', 100.0)
Parameter('INPUT_EGF_eq', 0.0)
Parameter('EGF_0', 0.0)
Parameter('EGF_EGF_koff', 0.1)
Parameter('EGF_EGF_kd', 1.0)
Parameter('ERBB2_degradation_kdeg', 1.0)
Parameter('ERBB2_eq', 100.0)
Parameter('INPUT_ERBB2_eq', 0.0)
Parameter('ERBB2_phosphorylation_Y1248_base_kcat', 1.0)
Parameter('ERBB2_dephosphorylation_Y1248_base_kcat', 1.0)
Parameter('INPUT_ERBB2_phosphorylation_Y1248_base_kcat', 0.0)
Parameter('INPUT_ERBB2_dephosphorylation_Y1248_base_kcat', 0.0)
Parameter('ERBB2_phosphorylation_Y1248_EGF_kcat', 1.0)
Parameter('INPUT_ERBB2_phosphorylation_Y1248_EGF_kcat', 0.0)
Expression('EGF_synthesis_ksyn', EGF_degradation_kdeg*EGF_eq)
Expression('EGF_synthesis_rate', EGF_synthesis_ksyn*INPUT_EGF_eq)
Expression('EGF_degradation_rate', EGF_degradation_kdeg)
Expression('EGF_ss', EGF_synthesis_rate/EGF_degradation_rate)
Expression('EGF_EGF_kon', EGF_EGF_kd*EGF_EGF_koff)
Expression('ERBB2_synthesis_ksyn', ERBB2_degradation_kdeg*ERBB2_eq)
Expression('ERBB2_synthesis_rate', ERBB2_synthesis_ksyn*INPUT_ERBB2_eq)
Expression('ERBB2_degradation_rate', ERBB2_degradation_kdeg)
Expression('ERBB2_ss', ERBB2_synthesis_rate/ERBB2_degradation_rate)
Expression('ERBB2_phosphorylation_Y1248_base_rate', ERBB2_phosphorylation_Y1248_base_kcat*INPUT_ERBB2_phosphorylation_Y1248_base_kcat)
Expression('ERBB2_dephosphorylation_Y1248_base_rate', ERBB2_dephosphorylation_Y1248_base_kcat*INPUT_ERBB2_dephosphorylation_Y1248_base_kcat)
Observable('EGF_obs', EGF(inh=None))
Observable('tEGF', EGF())
Observable('tEGF_ext', EGF_ext())
Observable('tERBB2', ERBB2())
Parameter('pMAPK3_Y204_scale', 1.0)
Parameter('pMAPK3_Y204_offset', 1.0)
Parameter('pAKT1_T308_scale', 1.0)
Parameter('pAKT1_T308_offset', 1.0)
Parameter('pAKT1_S473_scale', 1.0)
Parameter('pAKT1_S473_offset', 1.0)
Parameter('pAKT2_T308_scale', 1.0)
Parameter('pAKT2_T308_offset', 1.0)
Parameter('pAKT2_S473_scale', 1.0)
Parameter('pAKT2_S473_offset', 1.0)
Parameter('pAKT3_T308_scale', 1.0)
Parameter('pAKT3_T308_offset', 1.0)
Parameter('pAKT3_S473_scale', 1.0)
Parameter('pAKT3_S473_offset', 1.0)
Expression('FL_synthesis_ksyn', FL_degradation_kdeg * FL_eq)
Expression('FL_synthesis_rate', FL_synthesis_ksyn * INPUT_FL_eq)
Expression('FL_degradation_rate', FL_degradation_kdeg)
Expression('FLT3_synthesis_ksyn', FLT3_degradation_kdeg * FLT3_eq)
Expression('FLT3_synthesis_rate', FLT3_synthesis_ksyn * INPUT_FLT3_eq)
Expression('FLT3_degradation_rate', FLT3_degradation_kdeg)
Expression(
'FLT3_phosphorylation_Y843_base_rate',
FLT3_phosphorylation_Y843_base_kcat *
INPUT_FLT3_phosphorylation_Y843_base_kcat)
Expression(
'FLT3_dephosphorylation_Y843_base_rate',
FLT3_dephosphorylation_Y843_base_kcat *
INPUT_FLT3_dephosphorylation_Y843_base_kcat)
Expression('STAT1_synthesis_ksyn', STAT1_degradation_kdeg * STAT1_eq)
Expression('STAT1_synthesis_rate', STAT1_synthesis_ksyn * INPUT_STAT1_eq)
def add_monomer_synth_deg(
m_name: str,
psites: Optional[Iterable[str]] = None,
nsites: Optional[Iterable[str]] = None,
asites: Optional[Iterable[str]] = None,
):
"""
Adds the respective monomer plus synthesis rules and basal
activation/deactivation rules for all activateable sites
:param m_name:
monomer name
:param psites:
phospho sites
:param nsites:
nucleotide sites
:param asites:
other activity encoding sites
"""
if psites is None:
psites = []
else:
psites = [site for psite in psites for site in psite.split('_')]
if nsites is None:
nsites = []
if asites is None:
asites = []
sites = psites + nsites + asites
m = Monomer(
m_name,
sites=[psite for psite in sites],
site_states={
site: ['u', 'p'] if site in psites else
['gdp', 'gtp'] if site in nsites else ['inactive', 'active']
for site in sites
})
kdeg = Parameter(f'{m_name}_degradation_kdeg', 1.0)
t = Parameter(f'{m_name}_eq', 100.0)
ksyn = Expression(f'{m_name}_synthesis_ksyn', t * kdeg)
syn_rate = Expression(f'{m_name}_synthesis_rate',
ksyn * get_autoencoder_modulator(t))
Rule(
f'synthesis_{m_name}', None >> m(
**{
site: 'u' if site in psites else 'gdp' if site in
nsites else 'inactive'
for site in sites
}), syn_rate)
deg_rate = Expression(f'{m_name}_degradation_rate', kdeg)
Rule(f'degradation_{m_name}', m() >> None, deg_rate)
# basal activation
for sites, labels, fstate, rstate in zip(
[psites, nsites, asites], [('phosphorylation', 'dephosphorylation'),
('gtp_exchange', 'gdp_exchange'),
('activation', 'deactivation')],
['p', 'gtp', 'active'], ['u', 'gdp', 'indactive']):
for site in sites:
kcats = [
Parameter(f'{m_name}_{label}_{site}_base_kcat', 1.0)
for label in labels
]
rates = [
Expression(f'{m_name}_{label}_{site}_base_rate',
kcat * get_autoencoder_modulator(kcat))
for kcat, label in zip(kcats, labels)
]
Rule(F'{m_name}_{site}_base',
m(**{site: fstate}) | m(**{site: rstate}), *rates)
return m
Parameter('Vm_f6', 0.18)
Parameter('Vm_f5', 0.22)
Parameter('k_f16', 0.01)
Parameter('k_f17', 0.014)
Parameter('kex_f7', 0.61)
Parameter('kin_f7', 0.046)
Parameter('kex_f10', 0.54)
Parameter('kin_f10', 0.04)
Parameter('kex_f9', 0.018)
Parameter('kin_f9', 0.0086)
Parameter('kex_f8', 0.26)
Parameter('kin_f8', 0.035)
Parameter('kex_f11', 0.013)
Parameter('kin_f11', 0.007)
Expression('Vext', 9.4e-13 * f)
Expression('Vcyt', 9.4e-13 * f)
Expression('Vnuc', 2.2e-13 * f)
Expression('Egf_0', 6.8e-7 * Vext * NA)
Expression('Egfr_0', 1.0e-7 * Vcyt * NA)
Expression('PLCg_0', 1.05e-7 * Vcyt * NA)
Expression('Shc_0', 1.5e-7 * Vcyt * NA)
Expression('Grb2_0', 8.5e-8 * Vcyt * NA)
Expression('Sos_0', 3.4e-8 * Vcyt * NA)
Expression('kp1', 3000000.0 * Vext**(-1) * NA**(-1))
Expression('kp2', 10000000.0 * Vcyt**(-1) * NA**(-1))
Expression('kp5', 30000000.0 * Vcyt**(-1) * NA**(-1))
Expression('kp7', 3000000.0 * Vcyt**(-1) * NA**(-1))
Expression('kp9', 1500000.0 * Vcyt**(-1) * NA**(-1))
Expression('kp10', 10000000.0 * Vcyt**(-1) * NA**(-1))
Expression('kp11', 2250000.0 * Vcyt**(-1) * NA**(-1))
Parameter('bind_DUSP_ERKphosphop_kf', 10.0)
Parameter('bind_DUSP_ERKphosphop_kD', 0.01)
Parameter('catalyze_DUSP_ERK_u_kcatr', 1.0)
Parameter('BRAF_0', 0.0)
Parameter('CRAF_0', 0.0)
Parameter('RAS_0', 0.0)
Parameter('MEK_0', 0.0)
Parameter('ERK_0', 0.0)
Parameter('GRB2_0', 0.0)
Parameter('SOS1_0', 0.0)
Parameter('pMEK_IF_scale', 1.0)
Parameter('pMEK_IF_offset', 0.1)
Parameter('pERK_IF_scale', 1.0)
Parameter('pERK_IF_offset', 0.1)
Expression('N_Avogadro', 6.02214076000000e+23)
Expression('volume', 1.00000000000000e-12)
Expression('m_Da_EGF', 6200.00000000000)
Expression('initRAFi', RAFi_0)
Expression('initMEKi', MEKi_0)
Expression('initEGF',
6.02214085854916e+23 * EGF_0 * (m_Da_EGF * N_Avogadro)**(-1))
Expression('bind_EGF_EGFR_kr', bind_EGF_EGFR_kD * bind_EGF_EGFR_kf)
Expression('Gf_bind_EGF_EGFR', log(bind_EGF_EGFR_kD))
Expression('Ea0_bind_EGF_EGFR',
-bind_EGF_EGFR_phi * log(bind_EGF_EGFR_kD) - log(bind_EGF_EGFR_kf))
Expression('bind_EGFR_EGFR_kr', bind_EGFR_EGFR_kD * bind_EGFR_EGFR_kf)
Expression('Gf_bind_EGFR_EGFR', log(bind_EGFR_EGFR_kD))
Expression(
'Ea0_bind_EGFR_EGFR',
-bind_EGFR_EGFR_phi * log(bind_EGFR_EGFR_kD) - log(bind_EGFR_EGFR_kf))
from model_cell_cycle_no_M import model
from sympy import log
from pysb import Expression, Model
model = Model('cell_cycle_no_M_ridge', base=model)
for par in model.parameters:
if par.name.startswith('r'):
Expression(f'{par.name}_obs', log(par))
def energyrule(name, pattern, phi, deltag):
if not isinstance(phi, (Parameter, Expression)):
phi = Expression('expr_%s_phi' % name, phi)
if not isinstance(deltag, (Parameter, Expression)):
deltag = Expression('expr_%s_deltag' % name, deltag)
return Rule(name, pattern, phi, deltag, energy=True)
Parameter('pMAP2K1_S222_scale', 1.0)
Parameter('pMAP2K1_S222_offset', 1.0)
Parameter('pMAP2K2_S222_scale', 1.0)
Parameter('pMAP2K2_S222_offset', 1.0)
Parameter('pMAP2K2_S226_scale', 1.0)
Parameter('pMAP2K2_S226_offset', 1.0)
Parameter('pMAPK1_T185_scale', 1.0)
Parameter('pMAPK1_T185_offset', 1.0)
Parameter('pMAPK1_Y187_scale', 1.0)
Parameter('pMAPK1_Y187_offset', 1.0)
Parameter('pMAPK3_T202_scale', 1.0)
Parameter('pMAPK3_T202_offset', 1.0)
Parameter('pMAPK3_Y204_scale', 1.0)
Parameter('pMAPK3_Y204_offset', 1.0)
Expression('FL_synthesis_ksyn', FL_degradation_kdeg * FL_eq)
Expression('FL_synthesis_rate', FL_synthesis_ksyn * INPUT_FL_eq)
Expression('FL_degradation_rate', FL_degradation_kdeg)
Expression('FLT3_synthesis_ksyn', FLT3_degradation_kdeg * FLT3_eq)
Expression('FLT3_synthesis_rate', FLT3_synthesis_ksyn * INPUT_FLT3_eq)
Expression('FLT3_degradation_rate', FLT3_degradation_kdeg)
Expression(
'FLT3_phosphorylation_Y843_base_rate',
FLT3_phosphorylation_Y843_base_kcat *
INPUT_FLT3_phosphorylation_Y843_base_kcat)
Expression(
'FLT3_dephosphorylation_Y843_base_rate',
FLT3_dephosphorylation_Y843_base_kcat *
INPUT_FLT3_dephosphorylation_Y843_base_kcat)
Expression('HRAS_synthesis_ksyn', HRAS_degradation_kdeg * HRAS_eq)
Expression('HRAS_synthesis_rate', HRAS_synthesis_ksyn * INPUT_HRAS_eq)
Observable('Atot', A())
Observable('Btot', B())
Observable('Ctot', C())
Observable('AB0', A(b=MultiState(None, None, None)), match='species')
Observable('AB1', A(b=MultiState(1, None, None)) % B(a=1), match='species')
Observable('AB2',
A(b=MultiState(1, 2, None)) % B(a=1) % B(a=2),
match='species')
Observable('AB3',
A(b=MultiState(1, 2, 3)) % B(a=1) % B(a=2) % B(a=3),
match='species')
Observable('AB_motif', A(b=1) % B(a=1))
Tag('x')
Expression('f_synth', k_synthC * AB_motif(x)**2)
# A synthesizes C with rate dependent on bound B
Rule('_R1', A() @ x >> A() @ x + C(), f_synth)
# A binds B
Rule('_R2', A(b=None) + B(a=None) | A(b=1) % B(a=1), kp, km)
# degradation of C
Rule('_R3', C() >> None, k_degrC)
Initial(A(b=MultiState(None, None, None)), Ab_b_b_0)
Initial(B(a=None), Ba_0)
Initial(C(), C_0)
model = Model('cell_cycle_no_M')
C = Monomer('live_cell',
sites=['cycle'],
site_states={'cycle': ['G1', 'G2', 'S']})
D = Monomer('dead_cell')
Observable('G1_obs', C(cycle='G1'))
Observable('S_obs', C(cycle='S'))
Observable('G2_plus_M_obs', C(cycle='G2'))
Observable('D_obs', D())
Rule('G1_S',
C(cycle='G1') >> C(cycle='S'),
Expression('rateG1S',
Parameter('kG1S', 0.1) * Parameter('rG1S', 0.1)))
Rule('S_G2',
C(cycle='S') >> C(cycle='G2'),
Expression('rateSG2',
Parameter('kSG2', 0.1) * Parameter('rSG2', 0.1)))
Rule(
'G2_M_G1',
C(cycle='G2') >> C(cycle='G1') + C(cycle='G1'),
Expression('rateG2MG1',
Parameter('kG2MG1', 0.1) * Parameter('rG2MG1', 0.1)))
Rule('death',
C() >> D(),
Expression('ratedeath',
