def fit_popen(x, p_ca, p_ip3, normalized=False, bounds=None, scaling=None):
# This function minimizes p_open vs. Ca2+ and IP3 from Ramos-Franco et al.(Biophys. J. 2000)
# Rescaled variables properly, according to normalization and config flags
x_rescaled = rescale_vector(x,
model='lra',
normalized=normalized,
bounds=bounds,
scaling=scaling)
d1 = x_rescaled[0]
d2 = x_rescaled[1]
d3 = x_rescaled[2]
d5 = x_rescaled[3]
a2 = x_rescaled[4]
# print d1,d2,d3,d5,a2
astro = models.Astrocyte(model='lra', d1=d1, d2=d2, d3=d3, d5=d5, a2=a2)
# Retrieve Ca2+ points
x_ca = p_ca[0]
x_ip3 = p_ip3[0]
# # p_open vs. IP3 was obtained with 0.25 uM free Ca2+
astro.popen(0.25, x_ip3)
po_ip3 = astro.po
# print po_ip3
# p_open vs. Ca2+ was obtained with 1 uM IP3
astro.popen(x_ca, 1.0)
po_ca = astro.po
# print po_ca
# LMSE of the two curves
fc = np.sum((po_ip3 - p_ip3[1])**2) + np.sum((po_ca - p_ca[1])**2)
# fc = np.sum((po_ip3-p_ip3[1])**2)
# fc = np.sum((po_ca - p_ca[1]) ** 2)
del astro # Clean object
return fc
def chi_optimize(method='pso',
parallel=False,
N_ind=100,
N_gen=30,
iset=0,
show_results=False,
dir='../data/',
file_name='chi_fit'):
# Load experimental data
N_set = 2
ca_data = svu.loaddata('../data/herzog_data.pkl')[0]
po_data = svu.loaddata('../data/fit_po.pkl')[0]
lr_data = svu.loaddata('../data/fit_lra.pkl')[0]
# Get boundary dictionary
bounds_dict = models.model_bounds(model='chi')
# Save effective bounds and scaling
bounds, scaling = bounds_for_exploration(bounds_dict, normalized=False)
# Prepare model parameters
c0 = 5.0
# c0 = 15.0
params = np.asarray(np.r_[po_data[[0, 1, 0, 2, 3]], lr_data[[0, 1]], c0,
iset])
args = (params, ca_data)
#-----------------------------------------------------------------------------------------------------------
# Effective evolution
#-----------------------------------------------------------------------------------------------------------
# Size parameters
# N_var = problem_dimension(model='lra')
N_individuals = N_ind
N_var = problem_dimension(model='chi')
N_generations = N_gen * N_var
# Tolerances
FTOL = 1e-6
XTOL = 1e-6
# prob = pg.problem(fit_problem('lra',args))
prob = pg.problem(fit_problem('chi', args))
# Optimization
# NOTE: We keep each algorithm self contained here because different setting of parameters for evolution are
# needed depending on the chose algorithm
if method == 'pso':
algo = pg.algorithm(
pg.pso(gen=N_generations, variant=5, neighb_type=4, max_vel=0.8))
elif method == 'bee':
algo = pg.algorithm(pg.bee_colony(gen=N_generations, limit=2))
elif method == 'de':
algo = pg.algorithm(pg.de(gen=N_generations, ftol=FTOL, tol=XTOL))
# Single-node optimation to run on local machine / laptop
# N_individuals = 100
# N_generations = 40 * N_var
# verbosity = 20
if not parallel:
verbosity = 20
algo.set_verbosity(verbosity)
pop = pg.population(prob, size=N_individuals)
pop = algo.evolve(pop)
best_fitness = pop.get_f()[pop.best_idx()]
print(best_fitness)
x_rescaled = rescale_vector(pop.champion_x,
model='chi',
normalized=True,
bounds=bounds,
scaling=scaling)
# Show results of fit
if show_results:
astro = models.Astrocyte(
model='chi',
d1=po_data[0],
d2=po_data[1],
d3=po_data[0],
d5=po_data[2],
a2=po_data[3],
c0=c0,
c1=0.5,
rl=0.1,
Ker=0.1,
rc=lr_data[0],
ver=lr_data[1],
vbeta=x_rescaled[0],
vdelta=x_rescaled[1],
v3k=x_rescaled[2],
r5p=x_rescaled[3],
ICs=np.asarray([x_rescaled[6], x_rescaled[4], x_rescaled[5]]))
options = su.solver_opts(t0=ca_data['time'][iset][0],
tfin=ca_data['time'][iset][-1],
dt=1e-4,
atol=1e-8,
rtol=1e-6,
method="gsl_msadams")
astro.integrate(algparams=options, normalized=True)
ca_trace = ca_data['smoothed'][iset]
plt.plot(ca_data['time'][0], ca_trace, 'k-', astro.sol['ts'],
astro.sol['ca'], 'r-')
plt.show()
else:
# Parallel version to run on cluster
N_evolutions = 100
N_islands = 10
# Initiate optimization
algo = pg.algorithm(
pg.pso(gen=N_generations, variant=5, neighb_type=4, max_vel=0.8))
archi = pg.archipelago(n=N_islands,
algo=algo,
prob=prob,
pop_size=N_individuals)
archi.evolve(N_evolutions)
archi.wait()
imin = np.argmin(archi.get_champions_f())
x_rescaled = rescale_vector(archi.get_champions_x()[imin],
model='chi',
normalized=True,
bounds=bounds,
scaling=scaling)
print archi.get_champions_f()[imin]
print x_rescaled
svu.savedata([x_rescaled], dir + file_name + '.pkl')
def popen_optimize(method='de-simple'):
# Load experimental data
p_open = svu.loaddata('../data/p_open.pkl')[0]
# Get boundary dictionary
# bounds_dict = models.model_bounds(model='lra')
bounds_dict = models.model_bounds(model='lra2')
# Save effective bounds and scaling
bounds, scaling = bounds_for_exploration(bounds_dict, normalized=False)
args = (p_open['ca'], p_open['ip3'])
#-----------------------------------------------------------------------------------------------------------
# Effective evolution
#-----------------------------------------------------------------------------------------------------------
# Size parameters
# N_var = problem_dimension(model='lra')
N_var = problem_dimension(model='lra2')
N_individuals = 100
N_generations = 500 * N_var
N_evolutions = 50
# Tolerances
FTOL = 1e-3
XTOL = 1e-3
# prob = pg.problem(fit_problem('lra',args))
prob = pg.problem(fit_problem('lra2', args))
# Optimization
# NOTE: We keep each algorithm self contained here because different setting of parameters for evolution are
# needed depending on the chose algorithm
if method == 'de-simple':
##-----------------
# # Single node
##-----------------
# algo = pg.algorithm(pg.de(gen=N_generations,F=0.75,CR=0.9,variant=6,ftol=FTOL,xtol=XTOL))
# algo = pg.algorithm(pg.de(gen=N_generations, ftol=1e-12, tol=1e-6))
# algo = pg.algorithm(pg.pso(gen=N_generations))
algo = pg.algorithm(pg.bee_colony(gen=N_generations))
algo.set_verbosity(100)
pop = pg.population(prob, size=N_individuals)
pop = algo.evolve(pop)
best_fitness = pop.get_f()[pop.best_idx()]
print(best_fitness)
x_rescaled = rescale_vector(pop.champion_x,
model='lra2',
normalized=True,
bounds=bounds,
scaling=scaling)
astro = models.Astrocyte(model='lra2',
d1=x_rescaled[0],
d2=x_rescaled[1],
d5=x_rescaled[2],
a2=x_rescaled[3])
astro.popen(p_open['ca'][0], 1.0)
po_ca = astro.po
astro.popen(0.25, p_open['ip3'][0])
po_ip3 = astro.po
print x_rescaled
svu.savedata([x_rescaled], '../data/fit_po.pkl')
plt.semilogx(p_open['ca'][0], p_open['ca'][1], 'k-', p_open['ca'][0],
po_ca, 'ro', p_open['ip3'][0], p_open['ip3'][1], 'm-',
p_open['ip3'][0], po_ip3, 'bo')
plt.show()
def fit_ca(x,
params,
ca_exp,
model='chi',
normalized=False,
bounds=None,
scaling=None):
# This function minimizes the SE of normalized calcium traces and solution from integration of the chi model
# Rescaled variables properly, according to normalization and config flags
# Retrieve fixed parameters
d1 = params[0]
d2 = params[1]
d3 = params[2]
d5 = params[3]
a2 = params[4]
c0 = params[5]
# Rescale from normalized to regular values
x_rescaled = rescale_vector(x,
model=model,
normalized=normalized,
bounds=bounds,
scaling=scaling)
if model == 'lra_fit':
# Retrieve independent variables
rc = x_rescaled[0]
ver = x_rescaled[1]
ip3 = x_rescaled[2]
C0 = x_rescaled[3]
h0 = x_rescaled[4]
# Set new ICs (ca_trace is a handle to a spline object)
ICs = np.asarray([C0, h0], dtype=float)
# Generate astrocyte model
astro = models.Astrocyte(model='lra',
c1=0.5,
rl=0.1,
c0=c0,
Ker=0.1,
d1=d1,
d2=d2,
d3=d3,
d5=d5,
a2=a2,
ICs=ICs,
rc=rc,
ver=ver,
ip3=ip3)
elif model == 'chi':
# Retrieve case-specific fixed parameters
rc = params[6]
ver = params[7]
iset = int(params[8])
# Assign rescaled variables
vbeta = x_rescaled[0]
vdelta = x_rescaled[1]
v3k = x_rescaled[2]
r5p = x_rescaled[3]
C0 = x_rescaled[4]
h0 = x_rescaled[5]
I0 = x_rescaled[6]
# Set new ICs (ca_trace is a handle to a spline object)
ICs = np.asarray([I0, C0, h0], dtype=float)
# Generate astrocyte model
astro = models.Astrocyte(model='chi',
c1=0.5,
rl=0.1,
c0=c0,
Ker=0.1,
rc=rc,
ver=ver,
d1=d1,
d2=d2,
d3=d3,
d5=d5,
a2=a2,
ICs=ICs,
vbeta=vbeta,
vdelta=vdelta,
v3k=v3k,
r5p=r5p)
elif (model != 'pkc2') and ('pkc' in model):
rc = params[6]
ver = params[7]
r5p = params[8]
rtot = params[9]
yrel = x_rescaled[0]
vbeta = x_rescaled[1]
vdelta = x_rescaled[2]
v3k = x_rescaled[3]
vkp = x_rescaled[4]
vk = x_rescaled[5]
vd = x_rescaled[6]
# ICs
C0 = x_rescaled[7]
h0 = x_rescaled[8]
I0 = x_rescaled[9]
g0 = x_rescaled[10]
D0 = x_rescaled[11]
P0 = x_rescaled[12]
# Set new ICs (ca_trace is a handle to a spline object)
ICs = np.asarray([g0, I0, C0, h0, D0, P0], dtype=float)
# Generate astrocyte model
astro = models.Astrocyte(model='pkc',
c1=0.5,
rl=0.1,
c0=c0,
Ker=0.1,
rc=rc,
ver=ver,
d1=d1,
d2=d2,
d3=d3,
d5=d5,
a2=a2,
vbeta=vbeta,
vdelta=vdelta,
v3k=v3k,
r5p=r5p,
yrel=yrel,
vkp=vkp,
vk=vk,
vd=vd,
rtot=rtot,
ICs=ICs)
elif model == 'pkc2':
rc = params[6]
ver = params[7]
vbeta = params[8]
vdelta = params[9]
v3k = params[10]
r5p = params[11]
rtot = params[12]
yrel = x_rescaled[0]
Kkc = x_rescaled[1]
vkp = x_rescaled[2]
vk = x_rescaled[3]
vd = x_rescaled[4]
# ICs
C0 = x_rescaled[5]
h0 = x_rescaled[6]
I0 = x_rescaled[7]
g0 = x_rescaled[8]
D0 = x_rescaled[9]
P0 = x_rescaled[10]
# Set new ICs (ca_trace is a handle to a spline object)
ICs = np.asarray([g0, I0, C0, h0, D0, P0], dtype=float)
# Generate astrocyte model
astro = models.Astrocyte(model='pkc',
c1=0.5,
rl=0.01,
c0=c0,
Ker=0.1,
rc=rc,
ver=ver,
d1=d1,
d2=d2,
d3=d3,
d5=d5,
a2=a2,
vbeta=vbeta,
vdelta=vdelta,
v3k=v3k,
r5p=r5p,
yrel=yrel,
Kkc=Kkc,
vkp=vkp,
vk=vk,
vd=vd,
rtot=rtot,
ICs=ICs)
# Integrate
if model in ['lra_fit', 'chi']:
tfin = ca_exp['time'][0][-1]
elif 'pkc' in model:
tfin = ca_exp['time'][-1]
# 'lra' and 'chi'
ATOL = 1e-8
RTOL = 1e-6
# 'pkc'
ATOL = 1e-4
RTOL = 1e-4
options = su.solver_opts(t0=0.0,
tfin=tfin,
dt=1e-2,
atol=ATOL,
rtol=RTOL,
method="gsl_msadams")
astro.integrate(algparams=options, normalized=True)
# Generate spline from solution for later comparison with experimental data
ca_sol = interpolate.UnivariateSpline(astro.sol['ts'],
astro.sol['ca'],
k=3,
s=0)
pkc_sol = interpolate.UnivariateSpline(astro.sol['ts'],
astro.sol['pkc'],
k=3,
s=0)
if model == 'lra_fit':
# Compute max/min
# _, md = relextrema(ca_exp['ca'])
mns, mxs = relextrema(astro.sol['ca'])
index = np.sort(np.r_[ca_exp['mean_imin'], ca_exp['mean_imax']])
# Fitness on max/min + number of oscillations
fc = np.sum((ca_sol(ca_exp['time'][0][index]) -
ca_exp['mean_smoothed'][index])**2)
fc += 1000. * ((np.size(mxs) - np.size(ca_exp['mean_imax']))**2 +
(np.size(mns) - np.size(ca_exp['mean_imin']))**2)
# fc += 1000. * ((np.size(mxs) - np.size(ca_exp['mean_imax'])) ** 2)
# Add mean oscillation amplitude
# fc += 1500.*(1.-(np.mean(ca_exp['mean_smoothed'][ca_exp['mean_imax']]) - np.mean(ca_exp['mean_smoothed'][ca_exp['mean_imin']]))/(np.mean(astro.sol['ca'][mxs])-np.mean(astro.sol['ca'][mns])))**2
# Add distance between oscillation amplitudes
if (np.size(mxs) == np.size(
ca_exp['mean_imax'])) and (np.size(mns) == np.size(
ca_exp['mean_imin'])):
fc += 2000. * np.sum(
(osc_amplitude(ca_exp['mean_smoothed'], ca_exp['mean_imin'],
ca_exp['mean_imax']) -
osc_amplitude(astro.sol['ca'], mns, mxs))**2)
else:
fc *= 1e6
# print fc
elif model == 'chi':
# (Same as 'lra_fit' but considering iset)
mns, mxs = relextrema(astro.sol['ca'])
index = np.sort(np.r_[ca_exp['imin'][iset], ca_exp['imax'][iset]])
# Fitness on max/min + number of oscillations
fc = np.sum((ca_sol(ca_exp['time'][iset][index]) -
ca_exp['smoothed'][iset][index])**2)
fc += 1000. * ((np.size(mxs) - np.size(ca_exp['imax'][iset]))**2 +
(np.size(mns) - np.size(ca_exp['imin'][iset]))**2)
# fc += 1000. * ((np.size(mxs) - np.size(ca_exp['imax'][iset])) ** 2)
# Add mean oscillation amplitude
# fc += 1500.*(1.-(np.mean(ca_exp['smoothed'][ca_exp['imax'][iset]]) - np.mean(ca_exp['smoothed'][ca_exp['imin'][iset]]))/(np.mean(astro.sol['ca'][mxs])-np.mean(astro.sol['ca'][mns])))**2
# Add distance between oscillation amplitudes and phase difference
if (np.size(mxs) == np.size(
ca_exp['imax'][iset])) and (np.size(mns) == np.size(
ca_exp['imin'][iset])):
fc += 2000. * np.sum(
(osc_amplitude(ca_exp['smoothed'][iset], ca_exp['imin'][iset],
ca_exp['imax'][iset]) -
osc_amplitude(astro.sol['ca'], mns, mxs))**2)
fc += 2000. * np.sum(
np.abs(ca_exp['time'][iset][ca_exp['imax'][iset]] -
astro.sol['ts'][mxs]))
else:
fc *= 1e6
del astro # Clean object
return fc
def pkc_effect(sim=False):
"""
Shows ExGChI and compare with data from Codazzi et al (CON 2001)
"""
# Load relevant data
ca_data = svu.loaddata('../data/codazzi_data.pkl')[0]
po_data = svu.loaddata('../data/fit_po.pkl')[0]
lr_data = svu.loaddata('../data/fit_lra.pkl')[0]
chi_data = svu.loaddata('../data/chi_fit_0_bee.pkl')[0]
if sim:
print "1. Simulate PKC dynamics according to Codazzi"
# yrel = 1.508
yrel = 1.48
# yrel = 1.448
c0 = 5.0
rc = 0.8 * lr_data[0]
ver = lr_data[1]
vbeta = 1.0
vdelta = chi_data[1]
v3k = 1.4 * chi_data[2]
r5p = chi_data[3]
vk = 1.0
vkd = 0.28
OmegaKD = 0.33
vd = 0.45
OmegaD = 0.26
astro = models.Astrocyte(model='pkc',
d1=po_data[0],
d2=po_data[1],
d3=po_data[0],
d5=po_data[2],
a2=po_data[3],
c1=0.5,
rl=0.01,
Ker=0.1,
rc=rc,
ver=ver,
Kkc=0.5,
Kkd=0.1,
Kdd=0.1,
c0=c0,
yrel=yrel,
vbeta=vbeta,
vdelta=vdelta,
v3k=v3k,
r5p=r5p,
vk=vk,
vkd=vkd,
OmegaKD=OmegaKD,
vd=vd,
OmegaD=OmegaD,
ICs=np.asarray(
[0.0, 0.05, 0.05, 0.9, 0.0, 0.0]))
# Preliminary integration to start from resting conditions
options = su.solver_opts(t0=0.0,
tfin=60.,
dt=1e-4,
atol=1e-4,
rtol=1e-4,
method="gsl_msadams")
astro.integrate(algparams=options, normalized=False)
# Update model with new ICs and add pulse train
options = su.solver_opts(t0=0.0,
tfin=ca_data['time'][-1],
dt=1e-4,
atol=1e-4,
rtol=1e-4,
method="gsl_msadams")
astro.ICs = np.r_[astro.sol['rec'][-1], astro.sol['ip3'][-1],
astro.sol['ca'][-1], astro.sol['h'][-1],
astro.sol['dag'], astro.sol['pkc']]
astro.integrate(algparams=options, normalized=False)
sol_fit = astro.sol
# _,sol_0,sol_1,sol_2 = svu.loaddata('../data/pkc_qual_fit.pkl')
# svu.savedata([sol_fit,sol_0,sol_1,sol_2],'../data/pkc_qual_fit.pkl')
# Second simulation
print "2. Show effect of O_K"
# First standard astrocyte without
astro.pars['yrel'] = 1.55
astro.pars['vkd'] = 0.0
astro.pars['vk'] = 0.0
options = su.solver_opts(t0=0.0,
tfin=30,
dt=1e-4,
atol=1e-4,
rtol=1e-4,
method="gsl_msadams")
astro.integrate(algparams=options, normalized=False)
sol_0 = astro.sol
astro.pars['vkd'] = 0.28
astro.pars['vk'] = 1.0
astro.integrate(algparams=options, normalized=False)
sol_1 = astro.sol
astro.pars['vk'] = 3.0
astro.integrate(algparams=options, normalized=False)
sol_2 = astro.sol
# Save data
svu.savedata([sol_fit, sol_0, sol_1, sol_2],
'../data/pkc_qual_fit.pkl')
# # Third simulation (requires PyDSTool)
print "3. Computing oscillation period (requires PyDSTool)"
# Effective computation
pkc0 = bif.compute_period(vkd=0.001, vk=0.001)
svu.savedata([pkc0], '../data/pkc_period_Ok.pkl')
pkc1 = bif.compute_period(vkd=0.28, vk=1.0)
svu.savedata([pkc0, pkc1], '../data/pkc_period_Ok.pkl')
pkc2 = bif.compute_period(vkd=0.28, vk=3.0)
svu.savedata([pkc0, pkc1, pkc2], '../data/pkc_period_Ok.pkl')
pkc3 = bif.compute_period(vkd=0.84, vk=1.0)
svu.savedata([pkc0, pkc1, pkc2, pkc3], '../data/pkc_period_Ok.pkl')
pkc4 = bif.compute_period(vkd=0.84, vk=3.0)
svu.savedata([pkc0, pkc1, pkc2, pkc3, pkc4],
'../data/pkc_period_Ok.pkl')
#---------------------------------------------------------------------
# Plot figure
#---------------------------------------------------------------------
# Load MPL default style
plt.style.use('figures.mplstyle')
# Load data
sol, pkc0, pkc1, pkc2 = svu.loaddata('../data/pkc_qual_fit.pkl')
colors = {'ctrl': '0.7'}
#---------------------------------------------------------------------------------------------------------
# Fit with experimental data
#---------------------------------------------------------------------------------------------------------
fig, ax = plt.subplots(nrows=2,
ncols=1,
figsize=(6, 5.5),
sharex=False,
gridspec_kw={
'height_ratios': [1, 1],
'top': 0.96,
'bottom': 0.12,
'left': 0.15,
'right': 0.95
})
# # Plot experimental data
ax[0].plot(ca_data['original']['ca'][:, 0],
normalize(ca_data['original']['ca'][:, 1]),
'k-',
label='Ca$^{2+}$')
ax[0].plot(ca_data['original']['pkc'][:, 0],
normalize(ca_data['original']['pkc'][:, 1]),
'r-',
label='cPKC$^*$')
# Plot solution
tclip = [3, 27]
# # Mask
cmn, _ = fd.relextrema(sol['ca'])
pmn, _ = fd.relextrema(sol['pkc'])
cbase = (sol['ca'][cmn].max() - sol['ca'][cmn].min()) / 2
# pbase = (sol['pkc'][pmn].max() - sol['pkc'][pmn].min())/2
cbase += sol['ca'][cmn].min()
pbase = sol['pkc'][pmn].min()
cmask = np.where((tclip[0] <= sol['ts']) & (sol['ts'] < tclip[1])
& (sol['ca'] > cbase))[0]
pmask = np.where((tclip[0] <= sol['ts']) & (sol['ts'] < tclip[1])
& (sol['pkc'] > pbase))[0]
# # Effective plotting
ax[1].plot(sol['ts'][cmask] - sol['ts'][cmask[0]],
normalize(sol['ca'][cmask], min=cbase), 'k-')
ax[1].plot(sol['ts'][pmask] - sol['ts'][cmask[0]],
normalize(sol['pkc'][pmask], min=pbase), 'r-')
# Fit Check
# ax[1].plot(sol['ts'], normalize(sol['ca']), 'k-')
# ax[1].plot(sol['ts'], normalize(sol['pkc']), 'r-')
# ax[0].plot(sol['ts'], sol['ca'], 'k-', sol['ts'][cmn], sol['ca'][cmn], 'ko', sol['ts'][[0,-1]], [cbase, cbase], 'b-', ms=6)
# ax[0].plot(sol['ts'], sol['pkc'], 'r-', sol['ts'][pmn], sol['pkc'][pmn], 'ro', ms=6)
# Adjust axes
pu.adjust_spines(ax[0], ['left', 'bottom'])
ax[0].set(xlim=(0., 140),
xticks=np.arange(0, 141, 35),
ylim=(-0.02, 1.05),
yticks=np.arange(0, 1.1, 0.5),
ylabel='Experimental\nTraces (n.u.)')
pu.adjust_spines(ax[1], ['left', 'bottom'])
ax[1].set(xlim=(0., 20),
xticks=np.arange(0., 30, 5),
ylim=(-0.02, 1.05),
yticks=np.arange(0, 1.1, 0.5),
xlabel='Time (s)',
ylabel='Simulated\nTraces (n.u.)')
# # Final adjustment of y-labels
pu.adjust_ylabels(ax, x_offset=-0.08)
# Add legend
ax[0].legend(loc='upper right', facecolor='w', edgecolor='none')
# Save figure
plt.savefig('../Figures/f4_pkc_model.eps', dpi=600)
# ---------------------------------------------------------------
# Build effect of O_k on period
# ---------------------------------------------------------------
fig, ax = plt.subplots(nrows=3,
ncols=1,
figsize=(6, 4.5),
sharex=False,
gridspec_kw={
'height_ratios': [1, 1, 1],
'top': 0.96,
'bottom': 0.12,
'left': 0.17,
'right': 0.95
})
# C
ax[0].plot(pkc0['ts'], pkc0['ca'], '-', color=colors['ctrl'])
ax[0].plot(pkc1['ts'], pkc1['ca'], 'k-')
ax[0].plot(pkc2['ts'], pkc2['ca'], 'k-.')
# D
# First line is a dummy one to add proper legend in this plot rather than on the top one
# ax[1].plot(pkc0['ts'][[0,1]],pkc0['dag'][[0,1]],'-',color=colors['ctrl'],label='$O_{K}=0$')
ax[1].plot(pkc0['ts'],
pkc0['dag'],
'-',
color=colors['ctrl'],
label='$O_{K}=0$')
ax[1].plot(pkc1['ts'],
pkc1['dag'],
'k-',
label='$O_{K}=1.0$ $\mu$M$^{-1}$s$^{-1}$')
ax[1].plot(pkc2['ts'],
pkc2['dag'],
'k-.',
label='$O_{K}=3.0$ $\mu$M$^{-1}$s$^{-1}$')
# P
ax[2].plot(pkc0['ts'],
pkc0['pkc'],
'-',
color=colors['ctrl'],
label='$O_{K}=0$')
ax[2].plot(pkc1['ts'],
pkc1['pkc'],
'k-',
label='$O_{K}=1.0$ $\mu$M$^{-1}$s$^{-1}$')
ax[2].plot(pkc2['ts'],
pkc2['pkc'],
'k-.',
label='$O_{K}=3.0$ $\mu$M$^{-1}$s$^{-1}$')
# Adjust axes
pu.adjust_spines(ax[0], ['left'])
ax[0].set(xlim=(0., 30),
xticks=[],
ylim=(-0.02, 0.6),
yticks=np.arange(0, 0.61, 0.2),
ylabel='Ca$^{2+}$\n($\mu$M)')
pu.adjust_spines(ax[1], ['left'])
ax[1].set(xlim=(0., 30),
xticks=[],
ylim=(-0.02, 0.41),
yticks=np.arange(0, 0.4, 0.1),
ylabel='DAG\n($\mu$M)')
pu.adjust_spines(ax[2], ['left', 'bottom'])
ax[2].set(
xlim=(0., 30),
xticks=np.arange(0., 31, 10),
ylim=(-0.01, 0.075),
yticks=np.arange(0, 0.071, 0.02),
yticklabels=[str(int(i * 1e3)) for i in np.arange(0, 0.071, 0.02)],
xlabel='Time (s)',
ylabel='cPKC$^{*}$\n(nM)')
# # Final adjustment of y-labels
pu.adjust_ylabels(ax, x_offset=-0.08)
# Add legend
ax[2].legend(loc='upper right', facecolor='w', edgecolor='none')
# Save figure
plt.savefig('../Figures/f4_pkc_osc_1.eps', dpi=600)
#---------------------------------------------------------------
# Plot period of oscillations
#---------------------------------------------------------------
p0, p1, p2, p3, p4 = svu.loaddata('../data/pkc_period_Ok.pkl')
fig, ax = plt.subplots(nrows=2,
ncols=1,
figsize=(6, 4.5),
sharex=False,
gridspec_kw={
'height_ratios': [1, 2],
'top': 0.96,
'bottom': 0.12,
'left': 0.17,
'right': 0.95
})
for i, p in enumerate([p0, p1, p2, p3, p4]):
# idx = (p['T'] > 3.5)
idx = np.argsort(p['T'][(p['T'] > 3.5)])[::-1]
if i == 3: idx = idx[0:-2]
p['T'] = p['T'][idx]
p['yrel'] = p['yrel'][idx]
mask = lambda period: np.argsort(1.0 / period)
ax[1].plot(p0['yrel'][mask(p0['T'])],
p0['T'][mask(p0['T'])],
'-',
color=colors['ctrl'],
label='O$_{KD}$=0')
ax[1].plot(p1['yrel'][mask(p1['T'])],
p1['T'][mask(p1['T'])],
'k-',
zorder=5,
label='O$_{KD}$=0.28 $\mu$Ms$^{-1}$')
ax[1].plot(p2['yrel'][mask(p2['T'])],
p2['T'][mask(p2['T'])],
'b-',
zorder=5,
label='O$_{KD}$=0.84 $\mu$Ms$^{-1}$')
ax[1].plot(p3['yrel'][mask(p3['T'])], p3['T'][mask(p3['T'])], 'k-.')
ax[1].plot(p4['yrel'][mask(p4['T'])], p4['T'][mask(p4['T'])], 'b-.')
# Adjust axes
ax[0].set_visible(False)
pu.adjust_spines(ax[1], ['left', 'bottom'])
ax[1].set(xlim=(1.4, 1.9),
xticks=np.arange(1.4, 1.95, 0.1),
ylim=(3.5, 15),
yticks=np.arange(4, 15.1, 3),
xlabel='Glu ($\mu$M)',
ylabel='Oscillation Period (s)')
# Add Legend
ax[1].legend(loc='upper right', facecolor='w', edgecolor='none')
# Save figure
plt.savefig('../Figures/f4_pkc_osc_2.eps', dpi=600)
plt.show()
def chi_model():
"""
Provide sample fits for sole ChI model.
"""
# Load MPL default style
plt.style.use('figures.mplstyle')
#--------------------------------------------------------------------------
# Plot open probability
#--------------------------------------------------------------------------
p_open = svu.loaddata('../data/p_open.pkl')[0]
po_data = svu.loaddata('../data/fit_po.pkl')[0]
# Load significant data
astro = models.Astrocyte(model='lra',
d1=po_data[0],
d2=po_data[1],
d3=po_data[0],
d5=po_data[2],
a2=po_data[3])
# # p_open vs. IP3 was obtained with 0.25 uM free Ca2+
astro.popen(0.25, p_open['ip3'][0])
po_ip3 = astro.po
# print po_ip3
# p_open vs. Ca2+ was obtained with 1 uM IP3
astro.popen(p_open['ca'][0], 1.0)
po_ca = astro.po
fig, ax = plt.subplots(nrows=1,
ncols=2,
figsize=(10, 4),
sharex=False,
gridspec_kw={
'top': 0.98,
'bottom': 0.15,
'left': 0.1,
'right': 0.98
})
ax[0].plot(p_open['ip3'][0],
p_open['ip3'][1],
'k^',
ms=10,
ls='none',
label=r'Ca$^{2+}$=25 nM')
ax[0].plot(p_open['ca'][0],
p_open['ca'][1],
'ko',
ms=10,
ls='none',
label=r'IP$_3$=1 $\mu$M')
ax[0].plot(p_open['ip3'][0], po_ip3, 'k--')
ax[0].plot(p_open['ca'][0], po_ca, 'k-')
# Adjust axes
pu.adjust_spines(ax[0], ['left', 'bottom'])
xticks = 10**np.arange(-2, 2.1, 1)
ax[0].set(xlim=(0.008, 500),
ylim=(0., 0.5),
yticks=np.arange(0., 0.51, 0.1),
xscale='log',
xlabel=r'Ca$^{2+}$, IP$_3$ ($\mu$M)',
ylabel='IP$_3$R open probability')
ax[0].set(xticks=xticks, xticklabels=([str(xt) for xt in xticks]))
# Add legend
ax[0].legend(loc='lower right', facecolor='w', edgecolor='none')
#--------------------------------------------------------------------------
# Plot ChI model from data
#--------------------------------------------------------------------------
# Load relevant data
ca_data = svu.loaddata('../data/herzog_data.pkl')[0]
lr_data = svu.loaddata('../data/fit_lra.pkl')[0]
c0 = 5.0
iset = 2
colors = {
'data': '0.65',
'ca': 'k',
'ip3': pu.hexc((44, 160, 44)),
'h': pu.hexc((23, 190, 207))
}
# Colors for different data sets
filename = 'chi_fit_0_bee'
x_rescaled = svu.loaddata('../data/' + filename + '.pkl')[0]
# Fitted data
astro = models.Astrocyte(
model='chi',
d1=po_data[0],
d2=po_data[1],
d3=po_data[0],
d5=po_data[2],
a2=po_data[3],
c0=c0,
c1=0.5,
rl=0.1,
Ker=0.1,
rc=lr_data[0],
ver=lr_data[1],
vbeta=x_rescaled[0],
vdelta=x_rescaled[1],
v3k=x_rescaled[2],
r5p=x_rescaled[3],
ICs=np.asarray([x_rescaled[6], x_rescaled[4], x_rescaled[5]]))
options = su.solver_opts(t0=ca_data['time'][iset][0],
tfin=ca_data['time'][iset][-1],
dt=1e-4,
atol=1e-8,
rtol=1e-6,
method="gsl_msadams")
astro.integrate(algparams=options, normalized=True)
# Original data
ax[1].plot(ca_data['time'][iset],
ca_data['original'][iset],
'.',
ms=4,
color=colors['data'],
ls='none')
# Fit data
ax[1].plot(astro.sol['ts'],
astro.sol['ca'],
'-',
color=colors['ca'],
label='C')
ax[1].plot(astro.sol['ts'],
astro.sol['h'],
'-',
color=colors['h'],
label='h')
ax[1].plot(astro.sol['ts'],
astro.sol['ip3'],
'-',
color=colors['ip3'],
label='I')
ax[1].set(xlim=(0, 30.),
xticks=np.arange(0, 31, 5),
ylim=(0., 1.01),
yticks=np.arange(0., 1.1, 0.2),
xlabel='Time (s)',
ylabel='$ChI$ variables (n.u.)')
pu.adjust_spines(ax[1], ['left', 'bottom'])
pu.adjust_ylabels(ax, x_offset=-0.1)
# Add legend
ax[1].legend(loc='lower right', facecolor='w', edgecolor='none')
del astro
plt.savefig('../Figures/f1_chi_model.eps', dpi=600)
plt.show()
def compute_thr(**kwargs):
"""
Simulation routine to compute CICR threshold
"""
# Load relevant data from fits
po_data = svu.loaddata('../data/fit_po.pkl')[0]
lr_data = svu.loaddata('../data/fit_lra.pkl')[0]
chi_data = svu.loaddata('../data/chi_fit_0_bee.pkl')[0]
# Control parameter set
pars = models.gchi_parameters(d1=po_data[0],
d2=po_data[1],
d3=po_data[0],
d5=po_data[2],
a2=po_data[3],
c0=10.0,
c1=0.5,
rl=0.1,
Ker=0.1,
rc=lr_data[0],
ver=10.0,
vbeta=0.8,
vdelta=2 * chi_data[1],
v3k=chi_data[3],
r5p=chi_data[3])
# Custom parameters
pars = gu.varargin(pars, **kwargs)
# Simulation duration
t0 = 0.0
tfin = 20.0
# Generate model
astro = models.Astrocyte(model='gchi',
d1=pars['d1'],
d2=pars['d2'],
d3=pars['d3'],
d5=pars['d5'],
a2=pars['a2'],
c0=pars['c0'],
c1=pars['c1'],
rl=pars['rl'],
Ker=pars['Ker'],
rc=pars['rc'],
ver=pars['ver'],
vbeta=pars['vbeta'],
vdelta=pars['vdelta'],
v3k=pars['v3k'],
r5p=pars['r5p'],
ICs=np.asarray([0.0, 0.05, 0.05, 0.9]))
options = su.solver_opts(t0=t0,
tfin=30.,
dt=1e-4,
atol=1e-8,
rtol=1e-6,
method="gsl_msadams")
# First run to seek resting state
astro.integrate(algparams=options, normalized=False)
# Update model with new ICs and add pulse train
options = su.solver_opts(t0=t0,
tfin=tfin,
dt=1e-4,
atol=1e-8,
rtol=1e-6,
method="gsl_msadams")
astro.ICs = np.r_[astro.sol['rec'][-1], astro.sol['ip3'][-1],
astro.sol['ca'][-1], astro.sol['h'][-1]]
astro.pars['T'] = tfin
astro.pars['pw'] = tfin
yb = np.arange(0.5, 5.0, 0.05)
# yb = np.arange(1.0, 3.0, 0.3)
Nt = np.size(yb)
# Allocate results
ca_traces = [None] * Nt
ip3_traces = [None] * Nt
bias_traces = [None] * Nt
for i in xrange(Nt):
astro.pars['yb'] = yb[i]
# Effective simulation
astro.integrate(algparams=options, normalized=False)
# Save results
ca_traces[i] = astro.sol['ca']
ip3_traces[i] = astro.sol['ip3']
bias_traces[i] = astro.bias(twin=[t0, tfin], dt=0.01)
traces = {
'yb': yb,
'ts': astro.sol['ts'],
'ca': ca_traces,
'ip3': ip3_traces,
'bias': bias_traces
}
del astro
gc.collect()
return traces, pars
def gchi_model():
"""
Simulation of the G-ChI model with some pulse function
"""
# Load relevant data from fits
po_data = svu.loaddata('../data/fit_po.pkl')[0]
lr_data = svu.loaddata('../data/fit_lra.pkl')[0]
chi_data = svu.loaddata('../data/chi_fit_0_bee.pkl')[0]
# Sample parameters
c0 = 10.0
ver = 10.0
vbeta = 0.8
v3k = chi_data[3]
# Simulation duration
t0 = 0.0
tfin = 10.0
# Generate model
astro = models.Astrocyte(model='gchi',
d1=po_data[0],
d2=po_data[1],
d3=po_data[0],
d5=po_data[2],
a2=po_data[3],
c0=c0,
c1=0.5,
rl=0.1,
Ker=0.1,
rc=lr_data[0],
ver=ver,
vbeta=vbeta,
vdelta=2 * chi_data[1],
v3k=v3k,
r5p=chi_data[3],
ICs=np.asarray([0.0, 0.05, 0.05, 0.9]))
options = su.solver_opts(t0=t0,
tfin=30.,
dt=1e-4,
atol=1e-8,
rtol=1e-6,
method="gsl_msadams")
# First run to seek resting state
astro.integrate(algparams=options, normalized=False)
# Update model with new ICs and add pulse train
options = su.solver_opts(t0=t0,
tfin=tfin,
dt=1e-4,
atol=1e-8,
rtol=1e-6,
method="gsl_msadams")
astro.ICs = np.r_[astro.sol['rec'][-1], astro.sol['ip3'][-1],
astro.sol['ca'][-1], astro.sol['h'][-1]]
astro.pars['T'] = (tfin - t0) / (3.0 * tfin)
astro.pars['pw'] = 0.15 * astro.pars['T']
astro.pars['yb'] = 8.
# Effective simulation
astro.integrate(algparams=options, normalized=True)
# Retrieve bias
bias = astro.bias(twin=[t0, tfin], dt=0.01)
# Retrieve production and degradation terms
prod = astro.ip3_production()
degr = astro.ip3_degradation()
#---------------------------------------------------------------------
# Plot figure
#---------------------------------------------------------------------
# Load MPL default style
plt.style.use('figures.mplstyle')
colors = {
'data': '0.65',
'ca': 'k',
'ip3': pu.hexc((44, 160, 44)),
'Jbeta': pu.hexc((255, 127, 14)), # Orange
'Jdelta': pu.hexc((31, 119, 180)), # Tourquois
'J3k': pu.hexc((214, 39, 40)), # DarkRed
'J5p': pu.hexc((227, 119, 194)) # Magenta
}
fig, ax = plt.subplots(nrows=5,
ncols=1,
figsize=(8, 6.5),
sharex=False,
gridspec_kw={
'height_ratios': [0.5, 3, 3, 3, 3],
'top': 0.96,
'bottom': 0.12,
'left': 0.14,
'right': 0.95
})
# Plot stimulation
ax[0].plot(bias[0], bias[1], 'k-')
ax[0].set(xlim=(t0, tfin),
xticks=[],
ylim=(-0.2, 1.05 * astro.pars['yb']),
yticks=[],
ylabel='Glu\n($\mu$M)')
pu.adjust_spines(ax[0], ['left'])
# Plot receptor activation
ax[1].plot(astro.sol['ts'], astro.sol['rec'], 'k-')
pu.adjust_spines(ax[1], ['left'])
ax[1].set(xlim=(t0, tfin),
xticks=[],
ylim=(0., 0.3),
yticks=np.arange(0., 0.31, 0.1),
ylabel='Ast. Rec.\n$\Gamma_A$')
# Plot Ca2+ / IP3
ax[2].plot(astro.sol['ts'],
astro.sol['ca'],
'-',
color=colors['ca'],
label='C')
ax[2].plot(astro.sol['ts'],
astro.sol['ip3'],
'-',
color=colors['ip3'],
label='I')
pu.adjust_spines(ax[2], ['left'])
ax[2].set(xlim=(t0, tfin),
xticks=[],
ylim=(-0.05, 1.01),
yticks=np.arange(0, 1.1, 0.5),
ylabel='Ca$^{2+}$, IP$_3$\n(n.u.)')
ax[2].legend(loc='lower right', facecolor='w', edgecolor='none')
# Plot IP3 production
ax[3].plot(astro.sol['ts'],
prod['Jbeta'],
'-',
color=colors['Jbeta'],
label=r'J$_\beta$')
ax[3].plot(astro.sol['ts'],
prod['Jdelta'],
'-',
color=colors['Jdelta'],
label=r'J$_\delta$')
ax[3].plot(astro.sol['ts'], prod['Jbeta'] + prod['Jdelta'], 'k--')
pu.adjust_spines(ax[3], ['left'])
ax[3].set(xlim=(t0, tfin),
xticks=[],
ylim=(-0.02, 0.2),
yticks=np.arange(0, 0.21, 0.1),
ylabel='IP$_3$ prod.\n($\mu$M/s)')
ax[3].legend(loc='lower right', facecolor='w', edgecolor='none')
# Plot IP3 degradation
ax[4].plot(astro.sol['ts'],
degr['J5p'],
'-',
color=colors['J5p'],
label=r'J$_{5P}$')
ax[4].plot(astro.sol['ts'],
degr['J3k'],
'-',
color=colors['J3k'],
label=r'J$_{3K}$')
ax[4].plot(astro.sol['ts'], degr['J5p'] + degr['J3k'], 'k--')
pu.adjust_spines(ax[4], ['left', 'bottom'])
ax[4].set(xlim=(t0, tfin),
xticks=np.arange(t0, tfin + 1, 2.),
ylim=(-0.05, 0.22),
yticks=np.arange(0, 0.21, 0.1),
xlabel='Time (s)',
ylabel='IP$_3$ degr.\n($\mu$M/s)')
ax[4].legend(loc='lower right', facecolor='w', edgecolor='none')
# Final adjustment of y-labels
pu.adjust_ylabels(ax, x_offset=-0.07)
del astro
plt.savefig('../Figures/f2_gchi_model.eps', dpi=600)
plt.show()
