dt, sigma_em_circadian, W, pi, N_theta, std_theta, period_theta,
l_boundaries_theta, w_theta, N_phi, std_phi, period_phi,
l_boundaries_phi, w_phi, N_amplitude_theta, mu_amplitude_theta,
std_amplitude_theta, gamma_amplitude_theta,
l_boundaries_amplitude_theta, N_background_theta, mu_background_theta,
std_background_theta, gamma_background_theta,
l_boundaries_background_theta, F
] = pickle.load(f)
pi = None #to start with distributions at equilibrium
W_init = copy.copy(W) #save to make a plot in the end
"""""" """""" """""" """ DISPLAY PARAMETERS """ """""" """""" ""
display_parameters_from_file(path, show=True)
"""""" """""" """""" """ CREATE HIDDEN VARIABLES """ """""" """""" ""
theta_var_coupled, amplitude_var, background_var \
= create_hidden_variables(l_parameters = l_parameters )
l_var = [theta_var_coupled, amplitude_var, background_var]
"""""" """""" """""" """ COMPUTE NB_TRACE_MAX """ """""" """""" ""
if cell == 'NIH3T3':
path = "Data/NIH3T3.ALL.2017-04-04/ALL_TRACES_INFORMATION.p"
dataClass = LoadData(path,
nb_traces,
temperature=temperature,
division=False)
else:
path = "Data/U2OS-2017-03-20/ALL_TRACES_INFORMATION_march_2017.p"
dataClass = LoadData(path,
nb_traces,
temperature=temperature,
division=True) #all thz U2OS divide
def test_potential(cell='NIH3T3', temperature=37):
"""
Compute the potential associated to the coupling function in the system of
coupled oscillators.
Parameters
----------
cell : string
Cell condition.
temperature : integer
Temperature condition.
"""
##################### LOAD OPTIMIZED PARAMETERS ##################
path = '../Parameters/Real/opt_parameters_div_'+str(temperature)+"_"\
+cell+'.p'
with open(path, 'rb') as f:
l_parameters = [
dt, sigma_em_circadian, W, pi, N_theta, std_theta, period_theta,
l_boundaries_theta, w_theta, N_phi, std_phi, period_phi,
l_boundaries_phi, w_phi, N_amplitude_theta, mu_amplitude_theta,
std_amplitude_theta, gamma_amplitude_theta,
l_boundaries_amplitude_theta, N_background_theta,
mu_background_theta, std_background_theta, gamma_background_theta,
l_boundaries_background_theta, F
] = pickle.load(f)
##################### DISPLAY PARAMETERS ##################
display_parameters_from_file(path, show=False)
##################### CREATE HIDDEN VARIABLES ##################
theta_var_coupled, amplitude_var, background_var \
= create_hidden_variables(l_parameters = l_parameters )
##################### COMPUTE POTENTIAL ##################
Fbis = F + w_theta
F_temp = np.hstack((Fbis, Fbis, Fbis))
F_temp = np.vstack((F_temp, F_temp, F_temp))
f = interpolate.interp2d(np.linspace(-2 * np.pi,
4 * np.pi,
3 * F.shape[0],
endpoint=False),
np.linspace(-2 * np.pi,
4 * np.pi,
3 * F.shape[1],
endpoint=False),
F_temp.T,
kind='cubic',
bounds_error=True)
U = np.zeros((N_theta, N_phi))
for idx_theta in range(N_theta):
for idx_phi in range(N_phi):
print(idx_theta, idx_phi)
U[idx_theta, idx_phi] = dblquad(
f, 0, theta_var_coupled.domain[idx_theta], lambda x: 0,
lambda x: theta_var_coupled.codomain[idx_phi])[0]
path = "../Results/Potential/U_" + str(temperature) + "_" + cell + '.p'
pickle.dump(U, open(path, "wb"))
plt.figure(figsize=(5 * 1.2, 5 * 1.2))
ax = plt.gca()
im = plt.imshow(U.T,
cmap='bwr',
vmin=-0.3,
vmax=0.3,
interpolation='spline16',
origin='lower')
#add_colorbar(im, label = r'Acceleration ($rad.h^{-1}$)')
plt.xlabel(r'Circadian phase $\theta$')
plt.ylabel(r'Cell-cycle phase $\phi$')
plt.tight_layout()
plt.savefig("../Results/Potential/U_" + str(temperature) + "_" + cell +
'.pdf')
plt.show()
plt.close()
def display_parameters(l_parameters, show, temperature = None, cell = None):
"""
Display all the parameters from a list.
Parameters
----------
l_parameters : list
List of parameters.
show : bool
Display the figures (e.g. coupling function, intial condition) or not.
temperature : integer
Temperature condition . 34, 37 or 40.
cell : string
Cell type. 'NIH3T3' or 'U2OS'.
"""
[dt, sigma_em_circadian, W, pi,
N_theta, std_theta, period_theta, l_boundaries_theta, w_theta,
N_phi, std_phi, period_phi, l_boundaries_phi, w_phi,
N_amplitude_theta, mu_amplitude_theta, std_amplitude_theta,
gamma_amplitude_theta, l_boundaries_amplitude_theta,
N_background_theta, mu_background_theta, std_background_theta,
gamma_background_theta, l_boundaries_background_theta,
F] = l_parameters
print("")
print("########## SIMULATION PARAMETERS ##########")
print("dt = ", dt)
print("sigma_em_circadian = ", sigma_em_circadian)
print("")
print("########## THETA PARAMETERS ##########")
print("N_theta = ", N_theta)
print("std_theta = ", std_theta)
print("period_theta = ", period_theta)
print("l_boundaries_theta = ", l_boundaries_theta)
print("w_theta = ", w_theta)
print("")
print("########## PHI PARAMETERS ##########")
print("N_phi = ", N_phi)
print("std_phi = ", std_phi)
print("period_phi = ", period_phi)
print("l_boundaries_phi = ", l_boundaries_phi)
print("w_phi = ", w_phi)
print("")
print("########## AMPLITUDE PARAMETERS ##########")
print("N_amplitude_theta = ", N_amplitude_theta)
print("mu_amplitude_theta = ", mu_amplitude_theta)
print("std_amplitude_theta = ", std_amplitude_theta)
print("gamma_amplitude_theta = ", gamma_amplitude_theta)
print("l_boundaries_amplitude_theta = ", l_boundaries_amplitude_theta)
print("")
print("########## BACKGROUND PARAMETERS ##########")
print("N_background_theta = ", N_background_theta)
print("mu_background_theta = ", mu_background_theta)
print("std_background_theta = ", std_background_theta)
print("gamma_background_theta = ", gamma_background_theta)
print("l_boundaries_background_theta = ", l_boundaries_background_theta)
print("")
theta_var_coupled, amplitude_var, background_var = \
create_hidden_variables(l_parameters = l_parameters)
if show:
if W is None:
print("No waveform recorded, default waveform used")
W= [((1+np.cos( np.array(theta)))/2)**1.6 for theta \
in theta_var_coupled.domain]
plt.plot(theta_var_coupled.domain, W)
plt.xlabel(r'$\theta$')
plt.ylabel(r'$s(\theta)$')
plt.title('circadian waveform')
plt.show()
plt.close()
W = np.append(W[int(N_theta/2):], W[:int(N_theta/2)])
plt.plot(theta_var_coupled.domain, W)
plt.xlabel(r'$\theta$')
plt.ylabel(r'$s(\theta)$')
plt.title('circadian waveform')
plt.show()
plt.close()
if F is None:
print("No coupling recorded, blank coupling used")
F = np.zeros((N_theta, N_phi))
def add_colorbar(im, aspect=20, pad_fraction=0.5, **kwargs):
"""Add a vertical color bar to an image plot."""
divider = axes_grid1.make_axes_locatable(im.axes)
width = axes_grid1.axes_size.AxesY(im.axes, aspect=1./aspect)
pad = axes_grid1.axes_size.Fraction(pad_fraction, width)
current_ax = plt.gca()
cax = divider.append_axes("right", size=width, pad=pad)
plt.sca(current_ax)
return im.axes.figure.colorbar(im, cax=cax, **kwargs)
plt.figure(figsize=(5*1.2,5*1.2))
ax = plt.gca()
#ax.grid(False)
im = plt.imshow(F.T, cmap=bwr, vmin=-0.3, vmax=0.3, \
interpolation='spline16', origin='lower',
extent=[0, 1,0, 1])
add_colorbar(im, label = r'Acceleration ($rad.h^{-1}$)')
plt.xlabel(r'Circadian phase $\theta$')
plt.ylabel(r'Cell-cycle phase $\phi$')
plt.plot([0,1],[0.22,0.22], '--', color = 'grey')
plt.text(x = 0.05, y = 0.14, s='G1', color = 'grey', fontsize=12)
plt.text(x = 0.06, y = 0.27, s='S', color = 'grey', fontsize=12)
plt.plot([0,1],[0.84,0.84], '--', color = 'grey')
plt.text(x = 0.05, y = 0.84-0.08, s='S/G2', color = 'grey', fontsize=12)
plt.text(x = 0.06, y = 0.84+0.05, s='M', color = 'grey', fontsize=12)
#plt.xlabel("Circadian phase")
#plt.ylabel("Cell-cycle phase")
#plt.title('Coupling Function')
plt.tight_layout()
try:
plt.savefig("../Results/Disp/F_inferred_"+str(temperature)+"_"\
+cell+'.pdf')
except:
pass
plt.show()
plt.close()
theta_domain = theta_var_coupled.domain
amplitude_domain = amplitude_var.domain
background_domain = background_var.domain
if pi is None:
print("No pi recorded, uniform distribution used")
pi_theta = theta_var_coupled.pi
pi_amplitude = amplitude_var.pi
pi_background = background_var.pi
else:
pi_theta = np.sum(pi, axis = (1,2))
pi_amplitude = np.sum(pi, axis = (0,2))
pi_background = np.sum(pi, axis = (0,1))
plt.plot(theta_domain, pi_theta)
plt.xlabel(r'$\theta$')
plt.ylabel(r'$pi(\theta)$')
plt.title('Initial circadian phase distribution')
plt.show()
plt.close()
plt.plot(amplitude_domain, pi_amplitude)
plt.xlabel(r'$A$')
plt.ylabel(r'$pi(A)$')
plt.title('Initial amplitude distribution')
plt.show()
plt.close()
plt.plot(background_domain, pi_background)
plt.xlabel(r'$B$')
plt.ylabel(r'$pi(B)$')
plt.title('Initial background distribution')
plt.show()
plt.close()
def compute_phase_for_phase_delay(path=None, temperature=None):
"""
Compute phase of cells treated with various cell-cycle inhibitors and
write results in a text file to be analyzed with R.
Parameters
----------
path : string
Data path (if no temperature is given)
temperature : integer
Temperature condition (if no path is given)
"""
if path is None and temperature is None:
print('A PATH OR A TEMPERATURE MUST BE SPECIFIED')
##################### LOAD OPTIMIZED PARAMETERS ##################
path_par = '../Parameters/Real/opt_parameters_div_'+str(temperature)\
+'_NIH3T3.p'
with open(path_par, 'rb') as f:
l_parameters = [
dt, sigma_em_circadian, W, pi, N_theta, std_theta, period_theta,
l_boundaries_theta, w_theta, N_phi, std_phi, period_phi,
l_boundaries_phi, w_phi, N_amplitude_theta, mu_amplitude_theta,
std_amplitude_theta, gamma_amplitude_theta,
l_boundaries_amplitude_theta, N_background_theta,
mu_background_theta, std_background_theta, gamma_background_theta,
l_boundaries_background_theta, F
] = pickle.load(f)
##################### LOAD COLORMAP ##################
c = mcolors.ColorConverter().to_rgb
bwr = make_colormap(
[c('blue'),
c('white'), 0.48,
c('white'), 0.52,
c('white'),
c('red')])
##################### DISPLAY PARAMETERS ##################
display_parameters_from_file(path_par, show=True)
##################### LOAD DATA ##################
if temperature is not None:
path = "../Data/NIH3T3.ALL.2017-04-04/ALL_TRACES_INFORMATION.p"
dataClass = LoadData(path,
100000,
temperature=temperature,
division=True,
several_cell_cycles=False,
remove_odd_traces=True)
(ll_area, ll_signal, ll_nan_circadian_factor, ll_obs_phi, ll_peak,
ll_idx_cell_cycle_start, T_theta, T_phi)\
= dataClass.load(period_phi = None, load_annotation = True)
ll_idx_peak = [[idx for idx, v in enumerate(l_peak) if v>0] \
for l_peak in ll_peak]
print(len(ll_signal), " traces kept")
l_idx_trace = list(range(len(ll_area)))
else:
from os import listdir
from os.path import isfile, join
l_files = [f for f in listdir(path) if isfile(join(path, f))]
ll_t = []
ll_signal = []
ll_area = []
ll_peak = []
ll_neb = []
ll_cc_start = []
ll_nan_circadian_factor = []
ll_idx_cell_cycle_start = []
l_idx_trace = []
for file in l_files:
l_t = []
l_signal = []
l_area = []
l_peak = []
l_neb = []
l_cc_start = []
with open(path + '/' + file, 'r') as f:
for idx, line in enumerate(f):
if idx == 0: continue
t, signal, area, peak, cc_start, neb = line.split()
l_signal.append(float(signal))
l_area.append(float(area))
l_t.append(float(t))
l_peak.append(int(peak))
l_cc_start.append(int(cc_start))
l_neb.append(int(neb))
l_signal = np.array(l_signal) - np.percentile(l_signal, 5)
l_signal = l_signal / np.percentile(l_signal, 95)
garbage, idx_trace, garbage = file.split('.')
if np.sum(l_cc_start) >= 2:
l_idx_trace.append(int(idx_trace))
ll_t.append(l_t)
ll_signal.append(l_signal)
ll_area.append(l_area)
ll_peak.append(l_peak)
ll_neb.append(l_neb)
ll_cc_start.append(l_cc_start)
ll_peak.append(l_peak)
### NaN FOR CIRCADIAN SIGNAL ###
for l_mitosis_start, l_cell_start, l_peak in zip(
ll_neb, ll_cc_start, ll_peak):
l_temp = [False] * len(l_mitosis_start)
NaN = False
for ind, (m, c) in enumerate(zip(l_mitosis_start, l_cell_start)):
if m == 1:
NaN = True
if c == 1:
NaN = False
if NaN:
try:
l_temp[ind - 1] = True #TO BE REMOVED POTENTIALLY
except:
pass
try:
l_temp[ind + 1] = True
except:
pass
l_temp[ind] = True
ll_nan_circadian_factor.append(l_temp)
### COMPUTE IDX PHI ###
zp = zip(enumerate(ll_neb), ll_cc_start)
for (idx, l_mitosis_start), l_cell_cycle_start in zp:
l_idx_cell_cycle_start = \
[idx for idx, i in enumerate(l_cell_cycle_start) if i==1]
ll_idx_cell_cycle_start.append(l_idx_cell_cycle_start)
### GET PHI OBS ###
ll_obs_phi = []
for l_signal, l_idx_cell_cycle_start in zip(ll_signal,
ll_idx_cell_cycle_start):
l_obs_phi = [-1] * l_idx_cell_cycle_start[0]
first = True
for idx_div_1, idx_div_2 in zip(l_idx_cell_cycle_start[:-1],
l_idx_cell_cycle_start[1:]):
if not first:
del l_obs_phi[-1]
l_obs_phi.extend([i%(2*np.pi) for i \
in np.linspace(0,2*np.pi,idx_div_2-idx_div_1+1)])
first = False
l_obs_phi.extend( [-1] * \
(len(l_signal)-l_idx_cell_cycle_start[-1]-1))
ll_obs_phi.append(l_obs_phi)
ll_idx_peak = [[idx for idx, v in enumerate(l_peak) if v>0] \
for l_peak in ll_peak]
##################### CREATE HIDDEN VARIABLES ##################
theta_var_coupled, amplitude_var, background_var = \
create_hidden_variables(l_parameters = l_parameters)
l_var = [theta_var_coupled, amplitude_var, background_var]
##################### CREATE AND RUN HMM ##################
hmm = HMM_SemiCoupled(l_var,
ll_signal,
sigma_em_circadian,
ll_obs_phi,
waveform=W,
ll_nan_factor=ll_nan_circadian_factor,
pi=pi,
crop=True)
l_gamma_div, l_logP_div = hmm.run(project=False)
##################### CROP SIGNALS FOR PLOTTING ##################
l_first = [[it for it, obj in enumerate(l_obs_phi) \
if obj!=-1][0] for l_obs_phi in ll_obs_phi]
l_last = [[len(l_obs_phi)-it-1 for it, obj \
in enumerate(l_obs_phi[::-1]) if obj!=-1][0] for l_obs_phi in ll_obs_phi]
ll_signal = [l_signal[first:last+1] for l_signal, first, last \
in zip(ll_signal, l_first, l_last)]
ll_area = [l_area[first:last+1] for l_area, first, last \
in zip(ll_area, l_first, l_last)]
ll_obs_phi = [l_obs_phi[first:last+1] for l_obs_phi, first, last \
in zip(ll_obs_phi, l_first, l_last)]
ll_idx_cell_cycle_start = [ [v for v in l_idx_cell_cycle_start \
if v>=first and v<=last ] for l_idx_cell_cycle_start, first, last \
in zip(ll_idx_cell_cycle_start, l_first, l_last)]
ll_idx_peak = [ [v for v in l_idx_peak if v>=first and v<=last ] \
for l_idx_peak, first, last in zip(ll_idx_peak, l_first, l_last)]
##################### CREATE ll_idx_obs_phi and ll_val_phi##################
ll_idx_obs_phi = []
for l_obs in ll_obs_phi:
l_idx_obs_phi = []
for obs in l_obs:
l_idx_obs_phi.append( int(round(obs/(2*np.pi) * \
len(theta_var_coupled.codomain )))\
%len(theta_var_coupled.codomain ) )
ll_idx_obs_phi.append(l_idx_obs_phi)
##################### PLOT FITS ##################
ll_esp_theta = []
for ((idx, signal), gamma, logP, area, l_obs_phi, l_idx_cell_cycle_start,
l_idx_peak) in zip(enumerate(ll_signal), l_gamma_div, l_logP_div,
ll_area, ll_obs_phi, ll_idx_cell_cycle_start,
ll_idx_peak):
plt_result = PlotResults(gamma,
l_var,
signal_model,
signal,
waveform=W,
logP=logP,
temperature=temperature,
cell='NIH3T3')
try:
E_model, E_theta, E_A, E_B \
= plt_result.plotEverythingEsperance(False, idx)
ll_esp_theta.append(E_theta)
except:
ll_esp_theta.append([-1] * len(signal))
('Trace ' + str(idx) + ' skipped !')
##################### RECORD INFERRED PHASES IN A TXT FILE ##################
longest_trace = np.max([len(trace) for trace in ll_signal])
print([len(trace) for trace in ll_signal])
print(longest_trace)
if temperature is None:
appendix = path.split('/')[-1]
else:
appendix = str(temperature)
with open('../Results/RawPhases/traces_theta_inferred_'\
+appendix+'.txt', 'w') as f_theta:
with open('../Results/RawPhases/traces_phi_inferred_'\
+appendix+'.txt', 'w') as f_phi:
zp = zip(l_idx_trace, ll_signal, ll_esp_theta, ll_obs_phi)
for idx, signal, l_esp_theta, l_obs_phi in zp:
f_theta.write(str(idx))
f_phi.write(str(idx))
for s in np.concatenate(
(l_esp_theta, [-1] * (longest_trace - len(signal)))):
if s != -1:
f_theta.write('\t' + str(s * 2 * np.pi))
else:
f_theta.write('\t' + str(s))
for s in np.concatenate(
(l_obs_phi, [-1] * (longest_trace - len(signal)))):
f_phi.write('\t' + str(s))
f_theta.write('\n')
f_phi.write('\n')
def F_by_cell_cell_cycle_period(cell = 'NIH3T3', nb_traces = 10000,
size_block = 100, nb_iter = 15):
"""
Optimize and plot the coupling function and phase-space density at
different temperatures, but for a fixed distribution of cell-cycle periods.
Parameters
----------
cell : string
Cell condition.
nb_traces : int
How many traces to run the experiment on.
size_block : integer
Size of the traces chunks (to save memory).
nb_iter : int
Number of EM iterations.
"""
temperature = None
##################### LOAD COLORMAP ##################
c = mcolors.ColorConverter().to_rgb
bwr = make_colormap( [c('blue'), c('white'), 0.48, c('white'),
0.52,c('white'), c('red')])
##################### LOAD OPTIMIZED PARAMETERS ##################
path = '../Parameters/Real/opt_parameters_nodiv_'+str(temperature)\
+"_"+cell+'.p'
with open(path , 'rb') as f:
l_parameters = [dt, sigma_em_circadian, W, pi,
N_theta, std_theta, period_theta, l_boundaries_theta, w_theta,
N_phi, std_phi, period_phi, l_boundaries_phi, w_phi,
N_amplitude_theta, mu_amplitude_theta, std_amplitude_theta,
gamma_amplitude_theta, l_boundaries_amplitude_theta,
N_background_theta, mu_background_theta, std_background_theta,
gamma_background_theta, l_boundaries_background_theta,
F] = pickle.load(f)
##################### DISPLAY PARAMETERS ##################
display_parameters_from_file(path, show = False)
##################### LOAD TRACES ##################
dic_traces = {34:{}, 37:{}, 40:{}}
cell_cycle_space = list(range(12,40))
for T_cell_cycle in cell_cycle_space:
for temperature in [34,37,40]:
##################### LOAD DATA ##################
if cell == 'NIH3T3':
path = "../Data/NIH3T3.ALL.2017-04-04/ALL_TRACES_INFORMATION.p"
else:
path = "../Data/U2OS-2017-03-20/"\
+"ALL_TRACES_INFORMATION_march_2017.p"
dataClass=LoadData(path, nb_traces, temperature = temperature,
division = True, several_cell_cycles = False,
remove_odd_traces = True)
(ll_area_tot_flat, ll_signal_tot_flat,
ll_nan_circadian_factor_tot_flat, ll_obs_phi_tot_flat, ll_peak,
ll_idx_cell_cycle_start, T_theta, std_T_theta, T_phi, std_T_phi)\
= dataClass.load(period_phi = T_cell_cycle,
load_annotation = True,
force_temperature = True)
dic_traces[temperature][T_cell_cycle] = [ll_area_tot_flat,
ll_signal_tot_flat,
ll_nan_circadian_factor_tot_flat,
ll_obs_phi_tot_flat, ll_peak,
ll_idx_cell_cycle_start, T_theta,
std_T_theta, T_phi, std_T_phi]
#check that there is the same number of traces for a given temperature and
#given cell-cycle
for T_cell_cycle in cell_cycle_space:
max_nb = min(len(dic_traces[34][T_cell_cycle][0]),
len(dic_traces[37][T_cell_cycle][0]),
len(dic_traces[40][T_cell_cycle][0]))
dic_traces[34][T_cell_cycle] = [l[:max_nb] \
if type(l)==list else l for l in dic_traces[34][T_cell_cycle]]
dic_traces[37][T_cell_cycle] = [l[:max_nb] \
if type(l)==list else l for l in dic_traces[37][T_cell_cycle]]
dic_traces[40][T_cell_cycle] = [l[:max_nb] \
if type(l)==list else l for l in dic_traces[40][T_cell_cycle]]
print(len(dic_traces[34][T_cell_cycle][0]),
len(dic_traces[37][T_cell_cycle][0]),
len(dic_traces[40][T_cell_cycle][0]))
#merge all traces for a given temperature
for temperature in [34,37,40]:
print("Temperature : ", temperature)
(ll_area_tot_flat, ll_signal_tot_flat, ll_nan_circadian_factor_tot_flat,
ll_obs_phi_tot_flat, ll_peak, ll_idx_cell_cycle_start) \
= [], [], [], [], [], []
for T_cell_cycle in cell_cycle_space:
ll_area_tot_flat.extend(dic_traces[temperature][T_cell_cycle][0])
ll_signal_tot_flat.extend(dic_traces[temperature][T_cell_cycle][1])
ll_nan_circadian_factor_tot_flat.extend(
dic_traces[temperature][T_cell_cycle][2])
ll_obs_phi_tot_flat.extend(dic_traces[temperature][T_cell_cycle][3])
ll_peak.extend(dic_traces[temperature][T_cell_cycle][4])
ll_idx_cell_cycle_start.extend(
dic_traces[temperature][T_cell_cycle][5])
##################### SPECIFY F OPTIMIZATION CONDITIONS ##################
#makes algorithm go faster
only_F_and_pi = True
#we don't know the inital condiion when traces divide
pi = None
#we start with a random empty F
F = (np.random.rand( N_theta, N_phi)-0.5)*0.01
#regularization
lambda_parameter = 2*10e-6
lambda_2_parameter = 0.005
##################### CORRECT INFERENCE BIAS ##################
try:
F_no_coupling = pickle.load(open("../Parameters/Misc/F_no_coupling_"\
+str(37)+"_"+cell+'.p', "rb" ) )
for idx_theta in range(N_theta):
F_no_coupling[idx_theta,:] = np.mean(F_no_coupling[idx_theta,:])
except:
print("F_no_coupling not found, no bias correction applied")
F_no_coupling = None
##################### CORRECT PARAMETERS ACCORDINGLY ##################
l_parameters = [dt, sigma_em_circadian, W, pi,
N_theta, std_theta, period_theta, l_boundaries_theta, w_theta,
N_phi, std_phi, period_phi, l_boundaries_phi, w_phi,
N_amplitude_theta, mu_amplitude_theta, std_amplitude_theta,
gamma_amplitude_theta, l_boundaries_amplitude_theta,
N_background_theta, mu_background_theta, std_background_theta,
gamma_background_theta, l_boundaries_background_theta,
F]
##################### CREATE HIDDEN VARIABLES ##################
theta_var_coupled, amplitude_var, background_var = \
create_hidden_variables(l_parameters = l_parameters)
##################### CREATE BLOCK OF TRACES ##################
ll_area_tot = []
ll_signal_tot = []
ll_nan_circadian_factor_tot = []
ll_obs_phi_tot = []
first= True
zp = enumerate(zip(ll_area_tot_flat, ll_signal_tot_flat,
ll_nan_circadian_factor_tot_flat,
ll_obs_phi_tot_flat))
for index, (l_area, l_signal, l_nan_circadian_factor, l_obs_phi) in zp:
if index%size_block==0:
if not first:
ll_area_tot.append(ll_area)
ll_signal_tot.append(ll_signal)
ll_nan_circadian_factor_tot.append(ll_nan_circadian_factor)
ll_obs_phi_tot.append(ll_obs_phi)
else:
first = False
ll_area = [l_area]
ll_signal = [l_signal]
ll_nan_circadian_factor = [l_nan_circadian_factor]
ll_obs_phi = [l_obs_phi]
else:
ll_area.append(l_area)
ll_signal.append(l_signal)
ll_nan_circadian_factor.append(l_nan_circadian_factor)
ll_obs_phi.append(l_obs_phi)
#get remaining trace
ll_area_tot.append(ll_area)
ll_signal_tot.append(ll_signal)
ll_nan_circadian_factor_tot.append(ll_nan_circadian_factor)
ll_obs_phi_tot.append(ll_obs_phi)
##################### OPTIMIZATION ##################
def buildObsPhiFromIndex(ll_index):
ll_obs_phi = []
for l_index in ll_index:
l_obs_phi = []
for index in l_index:
if index==-1:
l_obs_phi.append(-1)
else:
l_obs_phi.append(index/N_theta*2*np.pi)
ll_obs_phi.append(l_obs_phi)
return ll_obs_phi
lP=0
l_lP=[]
l_idx_to_remove = []
for it in range(nb_iter):
print("Iteration :", it)
l_jP_phase = []
l_jP_amplitude = []
l_jP_background = []
l_gamma = []
l_gamma_0 = []
l_logP = []
ll_signal_hmm = []
ll_idx_phi_hmm = []
ll_nan_circadian_factor_hmm = []
### CLEAN TRACES AFTER FIRST ITERATION ###
if it==1:
ll_signal_tot_flat = ll_signal_hmm_clean
ll_idx_phi_tot_flat = ll_idx_phi_hmm_clean
ll_nan_circadian_factor_tot_flat = \
ll_nan_circadian_factor_hmm_clean
print("nb traces apres 1ere iteration : ",
len(ll_signal_tot_flat))
ll_signal_tot = []
ll_idx_phi_tot = []
ll_nan_circadian_factor_tot = []
ll_obs_phi_tot = []
first= True
zp = zip(enumerate(ll_signal_tot_flat),
ll_idx_phi_tot_flat,
ll_nan_circadian_factor_tot_flat)
for (index, l_signal), l_idx_phi, l_nan_circadian_factor in zp:
if index%size_block==0:
if not first:
ll_signal_tot.append(ll_signal)
ll_idx_phi_tot.append(ll_idx_phi)
ll_nan_circadian_factor_tot.append(
ll_nan_circadian_factor)
ll_obs_phi_tot.append(
buildObsPhiFromIndex(ll_idx_phi))
else:
first = False
ll_signal = [l_signal]
ll_idx_phi = [l_idx_phi]
ll_nan_circadian_factor = [l_nan_circadian_factor]
else:
ll_signal.append(l_signal)
ll_idx_phi.append(l_idx_phi)
ll_nan_circadian_factor.append(l_nan_circadian_factor)
#get remaining trace
ll_signal_tot.append(ll_signal)
ll_idx_phi_tot.append(ll_idx_phi)
ll_nan_circadian_factor_tot.append(ll_nan_circadian_factor)
ll_obs_phi_tot.append( buildObsPhiFromIndex(ll_idx_phi) )
zp = zip(ll_signal_tot, ll_obs_phi_tot, ll_nan_circadian_factor_tot)
for ll_signal, ll_obs_phi, ll_nan_circadian_factor in zp:
### INITIALIZE AND RUN HMM ###
l_var = [theta_var_coupled, amplitude_var, background_var]
hmm = HMM_SemiCoupled(l_var, ll_signal, sigma_em_circadian,
ll_val_phi = ll_obs_phi, waveform = W ,
ll_nan_factor = ll_nan_circadian_factor,
pi = pi, crop = True )
(l_gamma_0_temp, l_gamma_temp ,l_logP_temp, ll_alpha, ll_beta,
l_E, ll_cnorm, ll_idx_phi_hmm_temp, ll_signal_hmm_temp,
ll_nan_circadian_factor_hmm_temp) = hmm.run_em()
#crop and create ll_mat_TR
ll_signal_hmm_cropped_temp = [[s for s, idx in zip(l_s, l_idx) \
if idx>-1]\
for l_s, l_idx \
in zip(ll_signal_hmm_temp,
ll_idx_phi_hmm_temp)]
ll_idx_phi_hmm_cropped_temp = [[idx for idx in l_idx if idx>-1]\
for l_idx in ll_idx_phi_hmm_temp]
ll_mat_TR = [np.array( [theta_var_coupled.TR[:,idx_phi,:] \
for idx_phi in l_idx_obs_phi]) for l_idx_obs_phi \
in ll_idx_phi_hmm_cropped_temp]
l_jP_phase_temp, l_jP_amplitude_temp,l_jP_background_temp \
= EM.compute_jP_by_block(ll_alpha, l_E, ll_beta, ll_mat_TR,
amplitude_var.TR, background_var.TR,
N_theta, N_amplitude_theta,
N_background_theta, only_F_and_pi)
l_jP_phase.extend(l_jP_phase_temp)
l_jP_amplitude.extend(l_jP_amplitude_temp)
l_jP_background.extend(l_jP_background_temp)
l_gamma.extend(l_gamma_temp)
l_logP.extend(l_logP_temp)
l_gamma_0.extend(l_gamma_0_temp)
ll_signal_hmm.extend(ll_signal_hmm_temp)
ll_idx_phi_hmm.extend(ll_idx_phi_hmm_temp)
ll_nan_circadian_factor_hmm.extend(
ll_nan_circadian_factor_hmm_temp)
t_l_jP = (l_jP_phase, l_jP_amplitude,l_jP_background)
### REMOVE BAD TRACES IF FIRST ITERATION###
if it==0:
Plim = np.percentile(l_logP, 10)
#Plim = -10000
for idx_trace, P in enumerate(l_logP):
if P<=Plim:
l_idx_to_remove.append(idx_trace)
for index in sorted(l_idx_to_remove, reverse=True):
del t_l_jP[0][index]
del t_l_jP[1][index]
del t_l_jP[2][index]
del l_gamma[index]
del l_logP[index]
del l_gamma_0[index]
del ll_signal_hmm[index]
del ll_idx_phi_hmm[index]
del ll_nan_circadian_factor_hmm[index]
ll_signal_hmm_clean = copy.deepcopy(ll_signal_hmm)
ll_idx_phi_hmm_clean = copy.deepcopy(ll_idx_phi_hmm)
ll_nan_circadian_factor_hmm_clean \
= copy.deepcopy(ll_nan_circadian_factor_hmm)
### PARAMETERS UPDATE ###
[F_up, pi_up, std_theta_up, sigma_em_circadian_up, ll_coef,
std_amplitude_theta_up, std_background_theta_up, mu_amplitude_theta_up,
mu_background_theta_up, W_up] = EM.run_EM(l_gamma_0, l_gamma,
t_l_jP, theta_var_coupled, ll_idx_phi_hmm,
F, ll_signal_hmm, amplitude_var,
background_var, W,
ll_idx_coef = F_no_coupling,
only_F_and_pi = only_F_and_pi,
lambd_parameter = lambda_parameter,
lambd_2_parameter = lambda_2_parameter)
if np.mean(l_logP)-lP<10**-9:
print("diff:", np.mean(l_logP)-lP)
print(print("average lopP:", np.mean(l_logP)))
break
else:
lP = np.mean(l_logP)
print("average lopP:", lP)
l_lP.append(lP)
### CHOOSE NEW PARAMETERS ###
F = F_up
pi_up = pi
l_parameters = [dt, sigma_em_circadian, W, pi,
N_theta, std_theta, period_theta, l_boundaries_theta, w_theta,
N_phi, std_phi, period_phi, l_boundaries_phi, w_phi,
N_amplitude_theta, mu_amplitude_theta, std_amplitude_theta,
gamma_amplitude_theta, l_boundaries_amplitude_theta,
N_background_theta, mu_background_theta, std_background_theta,
gamma_background_theta, l_boundaries_background_theta,
F]
theta_var_coupled, amplitude_var, background_var = \
create_hidden_variables(l_parameters = l_parameters)
### PLOT COUPLING FUNCTION ###
plt.pcolormesh(theta_var_coupled.domain, theta_var_coupled.codomain,
F.T, cmap=bwr, vmin=-0.3, vmax=0.3)
plt.xlim([0, 2*np.pi])
plt.ylim([0, 2*np.pi])
plt.colorbar()
plt.xlabel("theta")
plt.ylabel("phi")
plt.show()
plt.close()
plt.plot(l_lP)
#plt.savefig("../Parameters/Real/opt_parameters_div_"+str(temperature)
#+"_"+cell+'_'+str(T_cell_cycle)+'.pdf')
plt.show()
plt.close()
##################### PLOT FINAL COUPLING ##################
def add_colorbar(im, aspect=20, pad_fraction=0.5, **kwargs):
###Add a vertical color bar to an image plot.###
divider = axes_grid1.make_axes_locatable(im.axes)
width = axes_grid1.axes_size.AxesY(im.axes, aspect=1./aspect)
pad = axes_grid1.axes_size.Fraction(pad_fraction, width)
current_ax = plt.gca()
cax = divider.append_axes("right", size=width, pad=pad)
plt.sca(current_ax)
return im.axes.figure.colorbar(im, cax=cax, **kwargs)
plt.figure(figsize=(5*1.2,5*1.2))
im = plt.imshow(F.T, cmap=bwr, vmin=-0.3, vmax=0.3,
interpolation='spline16', origin='lower',
extent=[0, 2*np.pi,0, 2*np.pi])
add_colorbar(im, label = r'Acceleration ($rad.h^{-1}$)')
plt.xlabel(r'Circadian phase $\theta$')
plt.ylabel(r'Cell-cycle phase $\phi$')
#plt.colorbar()
plt.xlabel(r'$\theta$')
plt.ylabel(r'$\phi$')
plt.title('T = ' + str(temperature))
plt.tight_layout()
plt.savefig("../Results/PhaseSpace/Coupling_"+str(temperature)\
+"_"+cell+'_demoind.pdf')
plt.close()
##################### PLOT PHASE SPACE DENSITY ##################
plot_phase_space_density(l_var, l_gamma, ll_idx_phi_tot_flat,
F_superimpose = None, save = True, cmap = bwr,
temperature = temperature, cell = cell,
period = T_cell_cycle,
folder = '../Results/PhaseSpace/' )
path = "../Results/PhaseSpace/Coupling_"+str(temperature)+"_"\
+cell+'_demoind.p'
with open(path, 'wb') as f:
pickle.dump(F, f)
def test_correlations(cell='NIH3T3', temperature=37, nb_traces=500):
"""
Compute and plot the correlation between the model variabels : phase, noise,
amplitude and background.
Parameters
----------
cell : string
Cell condition.
temperature : integer
Temperature condition.
nb_traces : integer
How many traces to run the experiment on.
"""
##################### LOAD OPTIMIZED PARAMETERS ##################
path = '../Parameters/Real/opt_parameters_div_'+str(temperature)\
+"_"+cell+'.p'
with open(path, 'rb') as f:
l_parameters = [
dt, sigma_em_circadian, W, pi, N_theta, std_theta, period_theta,
l_boundaries_theta, w_theta, N_phi, std_phi, period_phi,
l_boundaries_phi, w_phi, N_amplitude_theta, mu_amplitude_theta,
std_amplitude_theta, gamma_amplitude_theta,
l_boundaries_amplitude_theta, N_background_theta,
mu_background_theta, std_background_theta, gamma_background_theta,
l_boundaries_background_theta, F
] = pickle.load(f)
'''
gamma = 0.005
std_amplitude_theta = std_amplitude_theta \
* (gamma/gamma_amplitude_theta)**0.5
std_background_theta = std_background_theta \
* (gamma/gamma_background_theta)**0.5
gamma_amplitude_theta = gamma
gamma_background_theta = gamma
l_parameters = [dt, sigma_em_circadian, W, pi,
N_theta, std_theta, period_theta, l_boundaries_theta, w_theta,
N_phi, std_phi, period_phi, l_boundaries_phi, w_phi,
N_amplitude_theta, mu_amplitude_theta, std_amplitude_theta,
gamma_amplitude_theta, l_boundaries_amplitude_theta,
N_background_theta, mu_background_theta, std_background_theta,
gamma_background_theta, l_boundaries_background_theta,
F]
'''
##################### DISPLAY PARAMETERS ##################
display_parameters_from_file(path, show=True)
##################### LOAD DATA ##################
if cell == 'NIH3T3':
path = "../Data/NIH3T3.ALL.2017-04-04/ALL_TRACES_INFORMATION.p"
else:
path = "../Data/U2OS-2017-03-20/ALL_TRACES_INFORMATION_march_2017.p"
dataClass = LoadData(path,
nb_traces,
temperature=temperature,
division=True,
several_cell_cycles=False,
remove_odd_traces=True)
(ll_area, ll_signal, ll_nan_circadian_factor, ll_obs_phi, ll_peak,
ll_idx_cell_cycle_start, T_theta, T_phi) \
= dataClass.load(load_annotation = True)
ll_idx_peak = [[idx for idx, v in enumerate(l_peak) if v>0] \
for l_peak in ll_peak]
print(len(ll_signal), " traces kept")
##################### CREATE HIDDEN VARIABLES ##################
theta_var_coupled, amplitude_var, background_var \
= create_hidden_variables(l_parameters = l_parameters )
l_var = [theta_var_coupled, amplitude_var, background_var]
##################### CREATE AND RUN HMM ##################
hmm = HMM_SemiCoupled(l_var,
ll_signal,
sigma_em_circadian,
ll_obs_phi,
waveform=W,
ll_nan_factor=ll_nan_circadian_factor,
pi=pi,
crop=True)
l_gamma_div, l_logP_div = hmm.run(project=False)
##################### REMOVE BAD TRACES #####################
Plim = np.percentile(l_logP_div, 10)
idx_to_keep = [i for i, logP in enumerate(l_logP_div) if logP > Plim]
l_gamma_div = [l_gamma_div[i] for i in idx_to_keep]
ll_signal = [ll_signal[i] for i in idx_to_keep]
ll_area = [ll_area[i] for i in idx_to_keep]
l_logP_div = [l_logP_div[i] for i in idx_to_keep]
ll_obs_phi = [ll_obs_phi[i] for i in idx_to_keep]
ll_idx_cell_cycle_start = [ll_idx_cell_cycle_start[i] for i in idx_to_keep]
ll_idx_peak = [ll_idx_peak[i] for i in idx_to_keep]
print("Kept traces with div: ", len(idx_to_keep))
##################### CROP SIGNALS FOR PLOTTING ##################
l_first = [[it for it, obj in enumerate(l_obs_phi) \
if obj!=-1][0] for l_obs_phi in ll_obs_phi]
l_last = [[len(l_obs_phi)-it-1 for it, obj in enumerate(l_obs_phi[::-1]) \
if obj!=-1][0] for l_obs_phi in ll_obs_phi]
ll_signal = [l_signal[first:last+1] for l_signal, first, last \
in zip(ll_signal, l_first, l_last)]
ll_area = [l_area[first:last+1] for l_area, first, last \
in zip(ll_area, l_first, l_last)]
ll_obs_phi = [l_obs_phi[first:last+1] for l_obs_phi, first, last \
in zip(ll_obs_phi, l_first, l_last)]
ll_idx_cell_cycle_start = [ [v for v in l_idx_cell_cycle_start \
if v>=first and v<=last ] for l_idx_cell_cycle_start, first, last \
in zip(ll_idx_cell_cycle_start, l_first, l_last)]
ll_idx_peak = [ [v for v in l_idx_peak if v>=first and v<=last ] \
for l_idx_peak, first, last in zip(ll_idx_peak, l_first, l_last)]
##################### CREATE ll_idx_obs_phi and ll_val_phi##################
ll_idx_obs_phi = []
for l_obs in ll_obs_phi:
l_idx_obs_phi = []
for obs in l_obs:
l_idx_obs_phi.append( int(round(obs/(2*np.pi)\
*len(theta_var_coupled.codomain )))\
%len(theta_var_coupled.codomain))
ll_idx_obs_phi.append(l_idx_obs_phi)
##################### COMPUTE EXPECTED VALUE OF THE SIGNAL #################
ll_model = []
ll_phase = []
ll_amplitude = []
ll_background = []
zp = zip(enumerate(ll_signal), l_gamma_div, l_logP_div, ll_area,
ll_obs_phi, ll_idx_cell_cycle_start, ll_idx_peak)
for ((idx, signal), gamma, logP, area, l_obs_phi, l_idx_cell_cycle_start,
l_idx_peak) in zp:
plt_result = PlotResults(gamma,
l_var,
signal_model,
signal,
waveform=W,
logP=logP,
temperature=temperature,
cell=cell)
E_model, E_theta, E_A, E_B \
= plt_result.plotEverythingEsperance(False, idx)
ll_model.append(E_model)
ll_phase.append(E_theta)
ll_amplitude.append(E_A)
ll_background.append(E_B)
##################### COMPUTE AND PLOT RESIDUALS ##################
domain = list(range(N_theta))
dic_phase_res = {}
for phase in domain:
dic_phase_res[phase] = []
for (idx, l_signal), l_E_model, l_E_phase, in zip(enumerate(ll_signal),
ll_model, ll_phase):
for signal, E_model, E_phase in zip(l_signal, l_E_model, l_E_phase):
phase = int(round(E_phase * N_theta))
if phase == N_theta:
phase = 0
dic_phase_res[phase].append(E_model - signal)
l_mean = []
l_std = []
for phase in domain:
l_mean.append(np.mean(dic_phase_res[phase]))
l_std.append(np.std(dic_phase_res[phase]))
plt.close()
plt.errorbar(np.array(domain) / len(domain), l_mean, yerr=l_std, fmt='o')
plt.xlabel(r"Circadian phase $\theta$")
plt.ylabel(r"Residuals $S_t-O_t$")
plt.tight_layout()
plt.savefig('../Results/Correlation/Residuals_'+cell+'_'\
+str(temperature)+'.pdf')
plt.show()
plt.close()
##################### COMPUTE AND PLOT PHASE/AMP CORRELATION ###############
dic_phase_amp = {}
for phase in domain:
dic_phase_amp[phase] = []
for (idx, l_signal), l_E_amp, l_E_phase, in zip(enumerate(ll_signal),
ll_amplitude, ll_phase):
for signal, E_amp, E_phase in zip(l_signal, l_E_amp, l_E_phase):
phase = int(round(E_phase * N_theta))
if phase == N_theta:
phase = 0
dic_phase_amp[phase].append(E_amp)
l_mean = []
l_std = []
for phase in domain:
l_mean.append(np.mean(dic_phase_amp[phase]))
l_std.append(np.std(dic_phase_amp[phase]))
plt.errorbar(np.array(domain) / len(domain), l_mean, yerr=l_std, fmt='o')
plt.xlabel(r"Circadian phase $\theta$")
plt.ylabel(r"Amplitude Process $A_t$")
plt.tight_layout()
plt.savefig('../Results/Correlation/Amplitude_'+cell+'_'\
+str(temperature)+'.pdf')
plt.show()
plt.close()
##################### COMPUTE AND PLOT PHASE/BACK CORRELATION ##############
dic_phase_bac = {}
for phase in domain:
dic_phase_bac[phase] = []
for (idx, l_signal), l_E_bac, l_E_phase, in zip(enumerate(ll_signal),
ll_background, ll_phase):
for signal, E_bac, E_phase in zip(l_signal, l_E_bac, l_E_phase):
phase = int(round(E_phase * N_theta))
if phase == N_theta:
phase = 0
dic_phase_bac[phase].append(E_bac)
l_mean = []
l_std = []
for phase in domain:
l_mean.append(np.mean(dic_phase_bac[phase]))
l_std.append(np.std(dic_phase_bac[phase]))
plt.errorbar(np.array(domain) / len(domain), l_mean, yerr=l_std, fmt='o')
plt.xlabel(r"Circadian phase $\theta$")
plt.ylabel(r"Background Process $B_t$")
plt.tight_layout()
plt.savefig('../Results/Correlation/Background_'+cell+'_'\
+str(temperature)+'.pdf')
plt.show()
plt.close()
def before_after_opti(cell='NIH3T3',
temperature=37,
nb_traces=500,
size_block=100):
"""
Plot a trace fit before and after optimization of the parameters.
Parameters
----------
cell : string
Cell condition.
temperature : integer
Temperature condition.
nb_traces : integer
Number of traces from which the inference is made.
size_block : integer
Size of the traces chunks (to save memory).
"""
path = 'Parameters/Real/opt_parameters_div_' + str(
temperature) + "_" + cell + '.p'
"""""" """""" """""" """ LOAD OPTIMIZED PARAMETERS """ """""" """""" ""
with open(path, 'rb') as f:
l_parameters = [
dt, sigma_em_circadian, W, pi, N_theta, std_theta, period_theta,
l_boundaries_theta, w_theta, N_phi, std_phi, period_phi,
l_boundaries_phi, w_phi, N_amplitude_theta, mu_amplitude_theta,
std_amplitude_theta, gamma_amplitude_theta,
l_boundaries_amplitude_theta, N_background_theta,
mu_background_theta, std_background_theta, gamma_background_theta,
l_boundaries_background_theta, F
] = pickle.load(f)
"""""" """""" """""" """ DISPLAY PARAMETERS """ """""" """""" ""
display_parameters_from_file(path, show=False)
"""""" """""" """""" """ LOAD DATA """ """""" """""" ""
if cell == 'NIH3T3':
path = "Data/NIH3T3.ALL.2017-04-04/ALL_TRACES_INFORMATION.p"
else:
path = "Data/U2OS-2017-03-20/ALL_TRACES_INFORMATION_march_2017.p"
dataClass = LoadData(path,
nb_traces,
temperature=temperature,
division=True,
several_cell_cycles=False,
remove_odd_traces=True)
(ll_area, ll_signal, ll_nan_circadian_factor, ll_obs_phi, ll_peak,
ll_idx_cell_cycle_start, T_theta, T_phi) \
= dataClass.load(period_phi = None, load_annotation = True)
ll_idx_peak = [[idx for idx, v in enumerate(l_peak) if v>0] for \
l_peak in ll_peak]
print(len(ll_signal), " traces kept")
"""""" """""" """""" """ CREATE HIDDEN VARIABLES """ """""" """""" ""
theta_var_coupled, amplitude_var, background_var = \
create_hidden_variables(l_parameters = l_parameters)
l_var = [theta_var_coupled, amplitude_var, background_var]
"""""" """""" """""" """ CREATE AND RUN HMM WITH OPTI """ """""" """""" ""
hmm = HMM_SemiCoupled(l_var,
ll_signal,
sigma_em_circadian,
ll_obs_phi,
waveform=W,
ll_nan_factor=ll_nan_circadian_factor,
pi=pi,
crop=True)
l_gamma_div_1, l_logP_div_1 = hmm.run(project=False)
"""""" """""" """""" """ SET F TO 0 """ """""" """""" ""
l_parameters[-1] = np.zeros((N_theta, N_phi))
"""""" """""" """""" """ RECREATE HIDDEN VARIABLES """ """""" """""" ""
theta_var_coupled, amplitude_var, background_var = \
create_hidden_variables(l_parameters = l_parameters)
l_var = [theta_var_coupled, amplitude_var, background_var]
"""""" """""" """""" """ CREATE AND RUN HMM WITHOUT OPTI """ """""" """""" ""
hmm = HMM_SemiCoupled(l_var,
ll_signal,
sigma_em_circadian,
ll_obs_phi,
waveform=W,
ll_nan_factor=ll_nan_circadian_factor,
pi=pi,
crop=True)
l_gamma_div_2, l_logP_div_2 = hmm.run(project=False)
"""""" """""" """""" """ CROP SIGNALS FOR PLOTTING """ """""" """""" ""
l_first = [[it for it, obj in enumerate(l_obs_phi) if obj!=-1][0] \
for l_obs_phi in ll_obs_phi]
l_last = [[len(l_obs_phi)-it-1 for it, obj in enumerate(l_obs_phi[::-1]) \
if obj!=-1][0] for l_obs_phi in ll_obs_phi]
ll_signal = [l_signal[first:last+1] for l_signal, first, last \
in zip(ll_signal, l_first, l_last)]
ll_area = [l_area[first:last+1] for l_area, first, last \
in zip(ll_area, l_first, l_last)]
ll_obs_phi = [l_obs_phi[first:last+1] for l_obs_phi, first, last \
in zip(ll_obs_phi, l_first, l_last)]
ll_idx_cell_cycle_start = [ [v for v in l_idx_cell_cycle_start \
if v>=first and v<=last ] for l_idx_cell_cycle_start, first, last \
in zip(ll_idx_cell_cycle_start, l_first, l_last)]
ll_idx_peak = [ [v for v in l_idx_peak if v>=first and v<=last ] \
for l_idx_peak, first, last in zip(ll_idx_peak, l_first, l_last)]
"""""" """""" """""" """ PLOT FITS WITH """ """""" """""" ""
idx2 = 0
vmax = 0
imax = 0
zp = zip(enumerate(ll_signal), ll_area, ll_obs_phi,
ll_idx_cell_cycle_start, ll_idx_peak)
for (idx,
signal), area, l_obs_phi, l_idx_cell_cycle_start, l_idx_peak in zp:
plt_result = PlotResults(l_gamma_div_2[idx],
l_var,
signal_model,
signal,
waveform=W,
logP=l_logP_div_2[idx],
temperature=temperature,
cell=cell)
E_model1, E_theta, E_A, E_B = plt_result.plotEverythingEsperance(
True, idx2)
plt_result = PlotResults(l_gamma_div_1[idx],
l_var,
signal_model,
signal,
waveform=W,
logP=l_logP_div_1[idx],
temperature=temperature,
cell=cell)
E_model2, E_theta, E_A, E_B = plt_result.plotEverythingEsperance(
True, idx2 + 1)
vcur = np.sum(np.abs(np.array(E_model1)\
-np.array(E_model2)))/len(E_model1)
if vcur > vmax:
vmax = vcur
imax = idx
idx2 += 2
print(vmax, imax)
def load_F_by_cell_cycle(cell, nb_traces = 100, period = 22):
"""
Load the previously computed coupling function, recompute density and
superimpose determinstic attractor.
Parameters
----------
cell : string
Cell condition.
nb_traces : int
How many traces to run the experiment on.
period : int
Cell-cycle period used to simulate attractor.
"""
##################### LOAD COLORMAP ##################
c = mcolors.ColorConverter().to_rgb
bwr = make_colormap( [c('blue'), c('white'), 0.48, c('white'),
0.52,c('white'), c('red')])
##################### DISPLAY PARAMETERS ##################
#display_parameters_from_file(path, show = True)
dic_traces = {34:{}, 37:{}, 40:{}}
cell_cycle_space = list(range(12,40))
for T_cell_cycle in cell_cycle_space:
for temperature in [34,37,40]:
##################### LOAD DATA ##################
if cell == 'NIH3T3':
path = "../Data/NIH3T3.ALL.2017-04-04/ALL_TRACES_INFORMATION.p"
else:
path = "../Data/U2OS-2017-03-20/"\
+"ALL_TRACES_INFORMATION_march_2017.p"
dataClass=LoadData(path, nb_traces, temperature = temperature,
division = True, several_cell_cycles = False,
remove_odd_traces = True)
(ll_area_tot_flat, ll_signal_tot_flat,
ll_nan_circadian_factor_tot_flat, ll_obs_phi_tot_flat, ll_peak,
ll_idx_cell_cycle_start, T_theta, std_T_theta, T_phi, std_T_phi)\
= dataClass.load(period_phi = T_cell_cycle,
load_annotation = True,
force_temperature = True)
dic_traces[temperature][T_cell_cycle] = [ll_area_tot_flat,
ll_signal_tot_flat,
ll_nan_circadian_factor_tot_flat,
ll_obs_phi_tot_flat, ll_peak,
ll_idx_cell_cycle_start, T_theta,
std_T_theta, T_phi, std_T_phi]
#check that there is the same number of traces for a given temperature
#and given cell-cycle
for T_cell_cycle in cell_cycle_space:
max_nb = min(len(dic_traces[34][T_cell_cycle][0]),
len(dic_traces[37][T_cell_cycle][0]),
len(dic_traces[40][T_cell_cycle][0]))
dic_traces[34][T_cell_cycle] = [l[:max_nb] if type(l)==list \
else l for l in dic_traces[34][T_cell_cycle]]
dic_traces[37][T_cell_cycle] = [l[:max_nb] if type(l)==list \
else l for l in dic_traces[37][T_cell_cycle]]
dic_traces[40][T_cell_cycle] = [l[:max_nb] if type(l)==list \
else l for l in dic_traces[40][T_cell_cycle]]
print(len(dic_traces[34][T_cell_cycle][0]),
len(dic_traces[37][T_cell_cycle][0]),
len(dic_traces[40][T_cell_cycle][0]))
#merge all traces for a given temperature
for temperature in [34,37,40]:
print("Temperature : ", temperature)
(ll_area_tot_flat, ll_signal_tot_flat, ll_nan_circadian_factor_tot_flat,
ll_obs_phi_tot_flat, ll_peak, ll_idx_cell_cycle_start)\
= [], [], [], [], [], []
for T_cell_cycle in cell_cycle_space:
ll_area_tot_flat.extend(dic_traces[temperature][T_cell_cycle][0])
ll_signal_tot_flat.extend(dic_traces[temperature][T_cell_cycle][1])
ll_nan_circadian_factor_tot_flat.extend(
dic_traces[temperature][T_cell_cycle][2])
ll_obs_phi_tot_flat.extend(dic_traces[temperature][T_cell_cycle][3])
ll_peak.extend(dic_traces[temperature][T_cell_cycle][4])
ll_idx_cell_cycle_start.extend(
dic_traces[temperature][T_cell_cycle][5])
with open("../Results/PhaseSpace/Coupling_"+str(temperature)\
+"_"+cell+'_demoind.p', 'rb') as f:
F = pickle.load(f)
##################### PLOT FINAL COUPLING ##################
def add_colorbar(im, aspect=20, pad_fraction=0.5, **kwargs):
###Add a vertical color bar to an image plot.###
divider = axes_grid1.make_axes_locatable(im.axes)
width = axes_grid1.axes_size.AxesY(im.axes, aspect=1./aspect)
pad = axes_grid1.axes_size.Fraction(pad_fraction, width)
current_ax = plt.gca()
cax = divider.append_axes("right", size=width, pad=pad)
plt.sca(current_ax)
return im.axes.figure.colorbar(im, cax=cax, **kwargs)
plt.figure(figsize=(5*1.2,5*1.2))
im = plt.imshow(F.T, cmap=bwr, vmin=-0.3, vmax=0.3,
interpolation='spline16', origin='lower',
extent=[0, 1,0, 1])
add_colorbar(im, label = r'Acceleration ($rad.h^{-1}$)')
plt.xlabel(r'Circadian phase $\theta$')
plt.ylabel(r'Cell-cycle phase $\phi$')
#plt.colorbar()
plt.title('T = ' + str(temperature))
plt.tight_layout()
plt.savefig("../Results/PhaseSpace/Coupling_"+str(temperature)+"_"\
+cell+'_demoind.pdf')
plt.close()
##################### LOAD OPTIMIZED PARAMETERS ##################
path = '../Parameters/Real/opt_parameters_div_'+str(temperature)\
+"_"+cell+'.p'
with open(path, 'rb') as f:
l_parameters = [dt, sigma_em_circadian, W, pi,
N_theta, std_theta, period_theta, l_boundaries_theta, w_theta,
N_phi, std_phi, period_phi, l_boundaries_phi, w_phi,
N_amplitude_theta, mu_amplitude_theta, std_amplitude_theta,
gamma_amplitude_theta, l_boundaries_amplitude_theta,
N_background_theta, mu_background_theta, std_background_theta,
gamma_background_theta, l_boundaries_background_theta,
Ft] = pickle.load(f)
l_parameters[-1] = F
##################### CREATE HIDDEN VARIABLES ##################
theta_var_coupled, amplitude_var, background_var = \
create_hidden_variables(l_parameters = l_parameters)
l_var = [theta_var_coupled, amplitude_var, background_var]
##################### CREATE AND RUN HMM ##################
hmm=HMM_SemiCoupled(l_var, ll_signal_tot_flat, sigma_em_circadian,
ll_obs_phi_tot_flat, waveform = W,
ll_nan_factor = ll_nan_circadian_factor_tot_flat,
pi = pi, crop = True )
l_gamma_div, l_logP_div = hmm.run(project = False)
##################### REMOVE BAD TRACES #####################
Plim = np.percentile(l_logP_div, 1)
idx_to_keep = [i for i, logP in enumerate(l_logP_div) if logP>Plim ]
l_gamma_div = [l_gamma_div[i] for i in idx_to_keep]
ll_signal_tot_flat = [ll_signal_tot_flat[i] for i in idx_to_keep]
ll_area_tot_flat = [ll_area_tot_flat[i] for i in idx_to_keep]
ll_obs_phi_tot_flat = [ll_obs_phi_tot_flat[i] for i in idx_to_keep]
ll_idx_cell_cycle_start = [ll_idx_cell_cycle_start[i] \
for i in idx_to_keep]
print("Kept traces with div: ", len(idx_to_keep))
##################### CROP SIGNALS FOR PLOTTING ##################
l_first = [[it for it, obj in enumerate(l_obs_phi) if obj!=-1][0] \
for l_obs_phi in ll_obs_phi_tot_flat]
l_last = [[len(l_obs_phi)-it-1 for it, obj \
in enumerate(l_obs_phi[::-1]) if obj!=-1][0] \
for l_obs_phi in ll_obs_phi_tot_flat]
ll_signal = [l_signal[first:last+1] for l_signal, first, last \
in zip(ll_signal_tot_flat, l_first, l_last)]
ll_area = [l_area[first:last+1] for l_area, first, last \
in zip(ll_area_tot_flat, l_first, l_last)]
ll_obs_phi = [l_obs_phi[first:last+1] for l_obs_phi, first, last \
in zip(ll_obs_phi_tot_flat, l_first, l_last)]
ll_idx_cell_cycle_start = [[v for v in l_idx_cell_cycle_start \
if v>=first and v<=last ] \
for l_idx_cell_cycle_start, first, last \
in zip(ll_idx_cell_cycle_start, l_first, l_last)]
##################### CREATE ll_idx_obs_phi and ll_val_phi##################
ll_idx_obs_phi = []
for l_obs in ll_obs_phi:
l_idx_obs_phi = []
for obs in l_obs:
l_idx_obs_phi.append(int(round(obs/(2*np.pi) * \
len(theta_var_coupled.codomain )))\
%len(theta_var_coupled.codomain ))
ll_idx_obs_phi.append(l_idx_obs_phi)
##################### COMPUTE DETERMINISTIC ATTRACTOR ##################
#l_parameters[6] = T_theta
if period is not None:
l_parameters[11] = period
l_parameters[13] = 2*np.pi/period
#print(T_theta, T_phi)
detSim = DetSim(l_parameters, cell, temperature)
l_theta, l_phi = detSim.plot_trajectory(ti = 2500, tf = 3000,
rand = True, save = False )
print(T_phi)
##################### PLOT COUPLING AND PHASE SPACE DENSITY ############
plot_phase_space_density(l_var, l_gamma_div, ll_idx_obs_phi,
F_superimpose = F, save = True, cmap = bwr,
temperature = temperature, cell = cell,
period = T_phi, attractor = (l_theta, l_phi ),
folder = '../Results/PhaseSpace/' )
def phase_delay(cell='NIH3T3', temperature=37, nb_traces=500, size_block=100):
"""
Compute and plot how phase-delay evolves with the difference of intrinsic
periods between the two oscillators.
Parameters
----------
cell : string
Cell condition.
temperature : integer
Temperature condition.
nb_traces : integer
How many traces to run the experiment on.
size_block : integer
Size of the traces chunks (to save memory).
"""
l_delay = []
l_std_delay = []
l_T = [14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34]
l_real_T = []
l_real_std_T = []
#l_T = [20,22,24]
for period in l_T:
##################### LOAD OPTIMIZED PARAMETERS ##################
path = '../Parameters/Real/opt_parameters_div_'+str(temperature)\
+"_"+cell+'.p'
with open(path, 'rb') as f:
l_parameters = [
dt, sigma_em_circadian, W, pi, N_theta, std_theta,
period_theta, l_boundaries_theta, w_theta, N_phi, std_phi,
period_phi, l_boundaries_phi, w_phi, N_amplitude_theta,
mu_amplitude_theta, std_amplitude_theta, gamma_amplitude_theta,
l_boundaries_amplitude_theta, N_background_theta,
mu_background_theta, std_background_theta,
gamma_background_theta, l_boundaries_background_theta, F
] = pickle.load(f)
##################### DISPLAY PARAMETERS ##################
display_parameters_from_file(path, show=True)
##################### LOAD DATA ##################
if cell == 'NIH3T3':
path = "../Data/NIH3T3.ALL.2017-04-04/ALL_TRACES_INFORMATION.p"
else:
path = "../Data/U2OS-2017-03-20/ALL_TRACES_INFORMATION_march_2017.p"
dataClass = LoadData(path,
nb_traces,
temperature=temperature,
division=True,
several_cell_cycles=False,
remove_odd_traces=True)
(ll_area, ll_signal, ll_nan_circadian_factor, ll_obs_phi, ll_peak,
ll_idx_cell_cycle_start, T_theta, std_T_theta, T_phi, std_T_phi) = \
dataClass.load(period_phi = period, load_annotation = True)
l_real_T.append(24 - T_phi)
l_real_std_T.append(std_T_phi)
ll_idx_peak = [[idx for idx, v in enumerate(l_peak) if v>0] \
for l_peak in ll_peak]
print(len(ll_signal), " traces kept")
##################### CREATE HIDDEN VARIABLES ##################
theta_var_coupled, amplitude_var, background_var = \
create_hidden_variables(l_parameters = l_parameters)
l_var = [theta_var_coupled, amplitude_var, background_var]
##################### CREATE AND RUN HMM ##################
hmm = HMM_SemiCoupled(l_var,
ll_signal,
sigma_em_circadian,
ll_obs_phi,
waveform=W,
ll_nan_factor=ll_nan_circadian_factor,
pi=pi,
crop=True)
l_gamma_div, l_logP_div = hmm.run(project=False)
##################### REMOVE BAD TRACES #####################
Plim = np.percentile(l_logP_div, 10)
idx_to_keep = [i for i, logP in enumerate(l_logP_div) if logP > Plim]
l_gamma_div = [l_gamma_div[i] for i in idx_to_keep]
ll_signal = [ll_signal[i] for i in idx_to_keep]
ll_area = [ll_area[i] for i in idx_to_keep]
l_logP_div = [l_logP_div[i] for i in idx_to_keep]
ll_obs_phi = [ll_obs_phi[i] for i in idx_to_keep]
ll_idx_cell_cycle_start = [ll_idx_cell_cycle_start[i] \
for i in idx_to_keep]
ll_idx_peak = [ll_idx_peak[i] for i in idx_to_keep]
print("Kept traces with div: ", len(idx_to_keep))
##################### CROP SIGNALS FOR PLOTTING ##################
l_first = [[it for it, obj in enumerate(l_obs_phi) if obj!=-1][0] \
for l_obs_phi in ll_obs_phi]
l_last = [[len(l_obs_phi)-it-1 for it, obj in enumerate(l_obs_phi[::-1])\
if obj!=-1][0] for l_obs_phi in ll_obs_phi]
ll_signal = [l_signal[first:last+1] for l_signal, first, last \
in zip(ll_signal, l_first, l_last)]
ll_area = [l_area[first:last+1] for l_area, first, last \
in zip(ll_area, l_first, l_last)]
ll_obs_phi = [l_obs_phi[first:last+1] for l_obs_phi, first, last \
in zip(ll_obs_phi, l_first, l_last)]
ll_idx_cell_cycle_start = [ [v for v in l_idx_cell_cycle_start \
if v>=first and v<=last ] for l_idx_cell_cycle_start, first, last \
in zip(ll_idx_cell_cycle_start, l_first, l_last)]
ll_idx_peak = [ [v for v in l_idx_peak if v>=first and v<=last ] \
for l_idx_peak, first, last in zip(ll_idx_peak, l_first, l_last)]
##################### COMPUTE PHASE DELAY ##################
l_phase_delay = []
zp = zip(enumerate(ll_signal), l_gamma_div, l_logP_div, ll_area,
ll_obs_phi, ll_idx_cell_cycle_start, ll_idx_peak)
for ((idx, signal), gamma, logP, area, l_obs_phi,
l_idx_cell_cycle_start, l_idx_peak) in zp:
plt_result = PlotResults(gamma,
l_var,
signal_model,
signal,
waveform=W,
logP=logP,
temperature=temperature,
cell=cell)
l_E_model, l_E_theta, l_E_A, l_E_B \
= plt_result.plotEverythingEsperance(False, idx)
for phi, theta_unorm in zip(l_obs_phi, l_E_theta):
theta = theta_unorm * 2 * np.pi
if theta - phi > -np.pi and theta - phi < np.pi:
delay = theta - phi
elif theta - phi < -np.pi:
delay = theta + 2 * np.pi - phi
else:
delay = theta - phi - 2 * np.pi
l_phase_delay.append(delay)
l_delay.append(np.mean(l_phase_delay))
l_std_delay.append(np.std(l_phase_delay))
plt.errorbar(l_real_T,
l_delay,
xerr=l_real_std_T,
yerr=l_std_delay,
fmt='o')
plt.xlabel(r'$T_\theta-T_\phi$')
plt.ylabel("<" + r'$\theta$-$\phi$' + ">")
plt.savefig('../Results/PhaseBehavior/PhaseDelay_'+str(temperature)\
+"_" + cell+'.pdf')
plt.show()
plt.close()
def figure_1(cell='NIH3T3',
temperature=37,
nb_traces=1000,
size_block=100,
division=True):
"""
Create a nice plot to show data and fits.
Parameters
----------
cell : string
Cell condition.
temperature : integer
Temperature condition.
nb_traces : integer
How many traces to run the experiment on.
size_block : integer
Size of the traces chunks (to save memory).
division : bool
Plot dividing traces (True) or not (False).
"""
path = '../Parameters/Real/opt_parameters_div_'+str(temperature)+"_"\
+cell+'.p'
##################### LOAD OPTIMIZED PARAMETERS ##################
with open(path, 'rb') as f:
l_parameters = [
dt, sigma_em_circadian, W, pi, N_theta, std_theta, period_theta,
l_boundaries_theta, w_theta, N_phi, std_phi, period_phi,
l_boundaries_phi, w_phi, N_amplitude_theta, mu_amplitude_theta,
std_amplitude_theta, gamma_amplitude_theta,
l_boundaries_amplitude_theta, N_background_theta,
mu_background_theta, std_background_theta, gamma_background_theta,
l_boundaries_background_theta, F
] = pickle.load(f)
##################### DISPLAY PARAMETERS ##################
display_parameters_from_file(path, show=True)
##################### LOAD DATA ##################
if cell == 'NIH3T3':
path = "../Data/NIH3T3.ALL.2017-04-04/ALL_TRACES_INFORMATION.p"
else:
path = "../Data/U2OS-2017-03-20/ALL_TRACES_INFORMATION_march_2017.p"
dataClass = LoadData(path,
nb_traces,
temperature=temperature,
division=division,
several_cell_cycles=False,
remove_odd_traces=False)
(ll_area, ll_signal, ll_nan_circadian_factor, ll_obs_phi, ll_peak,
ll_idx_cell_cycle_start, T_theta, T_phi)\
= dataClass.load(period_phi = None, load_annotation = True)
print(len(ll_signal), " traces kept")
##################### CREATE HIDDEN VARIABLES ##################
theta_var_coupled, amplitude_var, background_var = \
create_hidden_variables(l_parameters = l_parameters)
l_var = [theta_var_coupled, amplitude_var, background_var]
##################### CREATE AND RUN HMM ##################
hmm = HMM_SemiCoupled(l_var,
ll_signal,
sigma_em_circadian,
ll_obs_phi,
waveform=W,
ll_nan_factor=ll_nan_circadian_factor,
pi=pi,
crop=False)
l_gamma_div, l_logP_div = hmm.run(project=False)
#keep only long traces
to_keep = [
i for i, l_signal in enumerate(ll_signal) if len(l_signal) > 100
]
ll_signal = [ll_signal[i][:100] for i in to_keep]
ll_area = [ll_area[i][:100] for i in to_keep]
if division:
ll_nan_circadian_factor =[ll_nan_circadian_factor[i][:100] \
for i in to_keep]
ll_obs_phi = [ll_obs_phi[i][:100] for i in to_keep]
ll_peak = [ll_peak[i][:100] for i in to_keep]
ll_idx_cell_cycle_start = [ [j for j in ll_idx_cell_cycle_start[i] \
if j<100] for i in to_keep]
ll_idx_peak = [[idx for idx, v in enumerate(l_peak) if v>0] \
for l_peak in ll_peak]
else:
ll_nan_circadian_factor = [[np.nan] * 100 for i in to_keep]
ll_obs_phi = [[np.nan] * 100 for i in to_keep]
ll_peak = [[np.nan] * 100 for i in to_keep]
ll_idx_cell_cycle_start = [[np.nan] for i in to_keep]
ll_idx_peak = [[np.nan] for l_peak in ll_peak]
l_gamma_div = [l_gamma_div[i][:100] for i in to_keep]
##################### PLOT #####################
waveform = interpolate.interp1d(
np.linspace(0, 2 * np.pi, len(W), endpoint=True), W)
current_palette = sn.color_palette()
for (idx, l_signal), l_nan_circadian_factor, l_idx_peak, l_idx_cc, gamma \
in zip(enumerate(ll_signal),
ll_nan_circadian_factor,
ll_idx_peak,
ll_idx_cell_cycle_start,
l_gamma_div):
if idx % 2 == 0:
plt.figure(figsize=(4, 3))
tspan = np.linspace(0, len(l_signal) / 2, len(l_signal))
plt.subplot(210 + idx % 2 + 1)
plt.plot(tspan, l_signal, '.', color = current_palette[0] \
if division else current_palette[1])
l_phase = []
l_A = []
l_B = []
l_model = []
for gamma_t in gamma:
phase = np.angle(
np.sum(
np.multiply(
np.sum(gamma_t, axis=(1, 2)),
np.exp(1j * np.array(theta_var_coupled.domain))))) % (
2 * np.pi)
A = np.sum(
np.multiply(np.sum(gamma_t, axis=(0, 2)),
amplitude_var.domain))
B = np.sum(
np.multiply(np.sum(gamma_t, axis=(0, 1)),
background_var.domain))
l_phase.append(phase)
l_A.append(A)
l_B.append(B)
l_model.append(signal_model([phase, A, B], waveform))
#plt.plot(tspan, [phase/(2*np.pi) for phase in l_phase], '--',
#color = 'grey')
#plt.plot(tspan, l_model, '-', color = current_palette[2])
for d in l_idx_cc:
plt.axvline(d / 2, color='black')
plt.ylim(-0.1, 1.1)
if idx % 2 == 1:
plt.tight_layout()
plt.savefig('../Results/Fits/GroupedFit_div_'+str(idx)+'_'\
+str(temperature)+"_"+cell+'.pdf' if division \
else '../Results/Fits/GroupedFit_nodiv_'+str(idx)\
+'_'+str(temperature)+"_"+cell+'.pdf')
plt.show()
plt.close()
'''
def stochastic_attractor_by_temperature(cell='NIH3T3',
nb_traces=500,
size_block=100,
expected=True):
"""
Compute and plot the evolution of the stochastic attractor with
temperature.
Parameters
----------
cell : string
Cell condition.
"""
ll_theta = []
ll_phi = []
l_temperature = [34, 37, 40]
l_color = ['lightblue', 'grey', 'orange']
for idx_t, temperature in enumerate(l_temperature):
##################### LOAD OPTIMIZED PARAMETERS ##################
path = '../Parameters/Real/opt_parameters_div_'+str(temperature)\
+"_"+cell+'.p'
with open(path, 'rb') as f:
l_parameters = [
dt, sigma_em_circadian, W, pi, N_theta, std_theta,
period_theta, l_boundaries_theta, w_theta, N_phi, std_phi,
period_phi, l_boundaries_phi, w_phi, N_amplitude_theta,
mu_amplitude_theta, std_amplitude_theta, gamma_amplitude_theta,
l_boundaries_amplitude_theta, N_background_theta,
mu_background_theta, std_background_theta,
gamma_background_theta, l_boundaries_background_theta, F
] = pickle.load(f)
##################### DISPLAY PARAMETERS ##################
display_parameters_from_file(path, show=False)
##################### LOAD DATA ##################
if cell == 'NIH3T3':
path = "../Data/NIH3T3.ALL.2017-04-04/ALL_TRACES_INFORMATION.p"
else:
path = "../Data/U2OS-2017-03-20/ALL_TRACES_INFORMATION_march_2017.p"
dataClass = LoadData(path,
nb_traces,
temperature=temperature,
division=True,
several_cell_cycles=True,
remove_odd_traces=True)
(ll_area, ll_signal, ll_nan_circadian_factor, ll_obs_phi, ll_peak,
ll_idx_cell_cycle_start, T_theta, T_phi) = \
dataClass.load(period_phi = None, load_annotation = True)
ll_idx_peak = [[idx for idx, v in enumerate(l_peak) if v>0] \
for l_peak in ll_peak]
print(len(ll_signal), " traces kept")
##################### CREATE HIDDEN VARIABLES ##################
theta_var_coupled, amplitude_var, background_var = \
create_hidden_variables(l_parameters = l_parameters)
l_var = [theta_var_coupled, amplitude_var, background_var]
##################### CREATE AND RUN HMM ##################
hmm = HMM_SemiCoupled(l_var,
ll_signal,
sigma_em_circadian,
ll_obs_phi,
waveform=W,
ll_nan_factor=ll_nan_circadian_factor,
pi=pi,
crop=True)
l_gamma_div, l_logP_div = hmm.run(project=False)
##################### REMOVE BAD TRACES #####################
Plim = np.percentile(l_logP_div, 10)
idx_to_keep = [i for i, logP in enumerate(l_logP_div) if logP > Plim]
l_gamma_div = [l_gamma_div[i] for i in idx_to_keep]
ll_signal = [ll_signal[i] for i in idx_to_keep]
ll_area = [ll_area[i] for i in idx_to_keep]
l_logP_div = [l_logP_div[i] for i in idx_to_keep]
ll_obs_phi = [ll_obs_phi[i] for i in idx_to_keep]
ll_idx_cell_cycle_start = [ll_idx_cell_cycle_start[i] for \
i in idx_to_keep]
ll_idx_peak = [ll_idx_peak[i] for i in idx_to_keep]
print("Kept traces with div: ", len(idx_to_keep))
##################### CROP SIGNALS FOR PLOTTING ##################
l_first = [[it for it, obj in enumerate(l_obs_phi) if obj!=-1][0] \
for l_obs_phi in ll_obs_phi]
l_last = [[len(l_obs_phi)-it-1 for it,obj in enumerate(l_obs_phi[::-1])\
if obj!=-1][0] for l_obs_phi in ll_obs_phi]
ll_signal = [l_signal[first:last+1] for l_signal, first, last \
in zip(ll_signal, l_first, l_last)]
ll_area = [l_area[first:last+1] for l_area, first, last \
in zip(ll_area, l_first, l_last)]
ll_obs_phi = [l_obs_phi[first:last+1] for l_obs_phi, first, last \
in zip(ll_obs_phi, l_first, l_last)]
ll_idx_cell_cycle_start = [ [v for v in l_idx_cell_cycle_start \
if v>=first and v<=last ] for l_idx_cell_cycle_start, first, last \
in zip(ll_idx_cell_cycle_start, l_first, l_last)]
ll_idx_peak = [ [v for v in l_idx_peak if v>=first and v<=last] \
for l_idx_peak, first, last in \
zip(ll_idx_peak, l_first, l_last)]
##################### CREATE ll_idx_obs_phi and ll_val_phi############
ll_idx_obs_phi = []
for l_obs in ll_obs_phi:
l_idx_obs_phi = []
for obs in l_obs:
l_idx_obs_phi.append( int(round(obs/(2*np.pi) \
* len(theta_var_coupled.codomain )))\
%len(theta_var_coupled.codomain ) )
ll_idx_obs_phi.append(l_idx_obs_phi)
if expected:
##################### GET EXPECTED PHASE ##################
M_at = plot_phase_space_density(l_var,
l_gamma_div,
ll_idx_obs_phi,
F_superimpose=F,
save=False)
l_theta = []
l_phi = []
for line, phi in zip(M_at.T, theta_var_coupled.domain):
l_theta.append( np.angle(
np.sum(
np.multiply(
line,np.exp(1j*\
np.array(theta_var_coupled.domain)
))))%(2*np.pi)
)
l_phi.append(phi)
else:
##################### GET MOST LIKELY PHASE ##################
M_at = plot_phase_space_density(l_var,
l_gamma_div,
ll_idx_obs_phi,
F_superimpose=F,
save=False)
l_theta = []
l_phi = []
for line, phi in zip(M_at.T, theta_var_coupled.domain):
idx_best_phase = np.argmax(line)
l_theta.append(theta_var_coupled.domain[idx_best_phase])
l_phi.append(phi)
######### REMOVE VERTICAL LINES AT BOUNDARIES #########
abs_d_data_x = np.abs(np.diff(l_theta))
mask_x = np.hstack([ abs_d_data_x > abs_d_data_x.mean()\
+3*abs_d_data_x.std(), [False]])
masked_l_theta = np.array([x if not m else np.nan \
for x,m in zip(l_theta, mask_x)])
abs_d_data_x = np.abs(np.diff(l_phi))
mask_x = np.hstack([ abs_d_data_x > abs_d_data_x.mean()\
+3*abs_d_data_x.std(), [False]])
masked_l_phi = np.array([x if not m else np.nan \
for x,m in zip(l_phi, mask_x) ])
ll_theta.append(masked_l_theta)
ll_phi.append(masked_l_phi)
######### COMPUTE IDENDITIY #########
#plot identity
x_domain = np.linspace(0, 2 * np.pi, 100)
f = (1.15 + np.linspace(0, 2 * np.pi, 100)) % (2 * np.pi)
abs_d_data_x = np.abs(np.diff(f))
mask_x = np.hstack([ abs_d_data_x > abs_d_data_x.mean()\
+3*abs_d_data_x.std(), [False]])
masked_identity = np.array([x if not m else np.nan \
for x, m in zip(f, mask_x)])
######### PLOT #########
plt.figure(figsize=(10, 10))
for idx_t, (l_phase_theta, l_phase_phi) in enumerate(zip(ll_theta,
ll_phi)):
plt.plot(l_phase_theta,
l_phase_phi,
color=l_color[idx_t],
label=str(l_temperature[idx_t]))
plt.plot(x_domain, masked_identity, '--')
plt.xlim(10**-2, 2 * np.pi - 10**-2)
plt.ylim(10**-2, 2 * np.pi - 10**-2)
plt.xlabel("Circadian phase")
plt.ylabel("Cell-cycle phase")
plt.legend()
plt.savefig('../Results/PhaseSpace/stochastic_attractor_by_temperature_' \
+str(expected)+'.pdf')
plt.show()
plt.close()
def test_coupling(cell='NIH3T3',
temperature=37,
test='cycle',
n_bins=15,
nb_traces=500):
"""
Compute the phase distribution of the cell-cycle/circadian clock for a given
circadian/cell-cycle phase, and compute the period distribution of the
cell-cycle/circadian clock for a given starting circadian/cell-cycle phase.
Parameters
----------
cell : string
Cell conditionself.
temperature : integer
Temperature condition.
test : string
'cycle' or clock, depending in which direction the coupling wants to be
test.
n_bins : int
How many bins to divide the phase domain in.
nb_traces : int
How many traces to run the experiment on.
"""
### LOAD DATA ###
if cell == 'NIH3T3':
path = "../Data/NIH3T3.ALL.2017-04-04/ALL_TRACES_INFORMATION.p"
else:
path = "../Data/U2OS-2017-03-20/ALL_TRACES_INFORMATION_march_2017.p"
dataClass = LoadData(path,
nb_traces,
temperature=temperature,
division=True,
several_cell_cycles=False)
(ll_area, ll_signal, ll_nan_circadian_factor, ll_obs_phi, ll_peak,
ll_idx_cell_cycle_start, T_theta, T_phi) = \
dataClass.load(load_annotation = True)
print(len(ll_signal), " traces in the dataset")
### KEEP ONLY REQUIRED TRACES ###
if test == 'cycle':
#print(ll_idx_cell_cycle_start[0])
to_keep = [idx for idx, l_idx_cc in enumerate(ll_idx_cell_cycle_start) \
if len(l_idx_cc)>=2 ]
elif test == 'clock':
l_first = [[it for it, obj in enumerate(l_obs_phi) if obj!=-1][0] \
for l_obs_phi in ll_obs_phi]
l_last =[[len(l_obs_phi)-it-1 for it, obj in enumerate(l_obs_phi[::-1])\
if obj!=-1][0] for l_obs_phi in ll_obs_phi]
ll_peak_after_crop =[[idx for idx, x in enumerate(l_peak[first:last+1])\
if x>0] for l_peak, first, last in zip(ll_peak, l_first, l_last)]
to_keep = [idx for idx, l_idx_cc in enumerate(ll_peak_after_crop) \
if len(l_idx_cc)>=2]
else:
print("Either clock or cycle can be tested")
ll_signal = [ll_signal[i] for i in to_keep]
ll_area = [ll_area[i] for i in to_keep]
ll_nan_circadian_factor = [ll_nan_circadian_factor[i] for i in to_keep]
ll_obs_phi = [ll_obs_phi[i] for i in to_keep]
ll_peak = [ll_peak[i] for i in to_keep]
ll_idx_cell_cycle_start = [ll_idx_cell_cycle_start[i] for i in to_keep]
ll_idx_peak = [[idx for idx, v in enumerate(l_peak) if v>0] \
for l_peak in ll_peak]
print(len(ll_signal), " traces kept")
### LOAD PARAMETERS ###
with open('../Parameters/Real/opt_parameters_nodiv_'+str(temperature)\
+"_"+cell+'.p', 'rb') as f:
l_parameters = [
dt, sigma_em_circadian, W, pi, N_theta, std_theta, period_theta,
l_boundaries_theta, w_theta, N_phi, std_phi, period_phi,
l_boundaries_phi, w_phi, N_amplitude_theta, mu_amplitude_theta,
std_amplitude_theta, gamma_amplitude_theta,
l_boundaries_amplitude_theta, N_background_theta,
mu_background_theta, std_background_theta, gamma_background_theta,
l_boundaries_background_theta, F
] = pickle.load(f)
##################### CREATE HIDDEN VARIABLES ###################
theta_var_coupled, amplitude_var, background_var = \
create_hidden_variables(l_parameters = l_parameters)
l_var = [theta_var_coupled, amplitude_var, background_var]
domain_theta = theta_var_coupled.domain
domain_phi = theta_var_coupled.codomain
##################### CREATE AND RUN HMM ###################
hmm = HMM_SemiCoupled(l_var,
ll_signal,
sigma_em_circadian,
ll_obs_phi,
waveform=W,
ll_nan_factor=ll_nan_circadian_factor,
pi=pi,
crop=True)
l_gamma_div, l_logP_div = hmm.run(project=False)
##################### REMOVE BAD TRACES ###################
Plim = np.percentile(l_logP_div, 10)
idx_to_keep = [i for i, logP in enumerate(l_logP_div) if logP > Plim]
l_gamma_div = [l_gamma_div[i] for i in idx_to_keep]
ll_signal = [ll_signal[i] for i in idx_to_keep]
ll_area = [ll_area[i] for i in idx_to_keep]
l_logP_div = [l_logP_div[i] for i in idx_to_keep]
ll_obs_phi = [ll_obs_phi[i] for i in idx_to_keep]
ll_idx_cell_cycle_start = [ll_idx_cell_cycle_start[i] for i in idx_to_keep]
print("Kept traces with div: ", len(idx_to_keep))
### CROP SIGNAL ###
l_first = [[it for it, obj in enumerate(l_obs_phi) if obj!=-1][0] \
for l_obs_phi in ll_obs_phi]
l_last = [[len(l_obs_phi)-it-1 for it, obj in enumerate(l_obs_phi[::-1]) \
if obj!=-1][0] for l_obs_phi in ll_obs_phi]
ll_signal = [l_signal[first:last+1] for l_signal, first, last \
in zip(ll_signal, l_first, l_last)]
ll_area = [l_area[first:last+1] for l_area, first, last \
in zip(ll_area, l_first, l_last)]
ll_obs_phi = [l_obs_phi[first:last+1] for l_obs_phi, first, last \
in zip(ll_obs_phi, l_first, l_last)]
ll_peak = [l_peak[first:last+1] for l_peak, first, last \
in zip(ll_peak, l_first, l_last)]
ll_idx_peak = [ [idx for idx, i in enumerate(l_peak) if i==1] \
for l_peak in ll_peak]
ll_idx_cc_start = [np.array(l_idx_cell_cycle_start)-first \
for l_idx_cell_cycle_start, first, last \
in zip(ll_idx_cell_cycle_start, l_first, l_last)]
### COMPUTE THE DISTRIBUTION OF CIRCADIAN PHASES AT PHI = 0 ###
ll_phase_clock = []
for gamma in l_gamma_div:
l_phase = []
for gamma_t in gamma:
p_phase = np.sum(gamma_t, axis=(1, 2))
phase = np.angle(
np.sum(np.multiply(p_phase, np.exp(
1j * domain_theta)))) % (2 * np.pi)
l_phase.append(phase)
ll_phase_clock.append(l_phase)
#keep only traces with at least a full cycle
if test == "cycle":
ll_idx = ll_idx_cc_start
ll_phase = ll_phase_clock
elif test == "clock":
ll_idx = ll_idx_peak
ll_phase = ll_obs_phi
else:
print("Either clock or cycle can be tested")
l_nb_cc = [(idx, len(l)) for idx, l in enumerate(ll_idx) if len(l) > 1]
#plot circadian ditribution at mitosis, or cycle distribution at peak
l_phase_mitosis = []
for idx_corr, (idx, nb_cc) in enumerate(l_nb_cc):
for i in range(nb_cc - 1):
l_phase_mitosis.append(ll_phase[idx][ll_idx[idx][i]])
df1 = pd.DataFrame({})
n, bins, patches = plt.hist(l_phase_mitosis,
bins=n_bins,
normed=False,
color='steelblue',
alpha=0.5)
df1['g1'] = pd.Series(l_phase_mitosis)
hist, edges = np.histogram(l_phase_mitosis)
max_val = max(hist)
plt.ylim([0, max_val])
plt.xlim([0, 2 * np.pi + 0.01])
#plt.title("N = " + str(len(l_phase_mitosis)))
if test == "cycle":
plt.xlabel('Circadian phase at mitosis')
plt.savefig('../Results/TestCoupling/'+cell+'_'\
+str(temperature)+'_circadian_phase_at_mitosis.pdf')
else:
plt.xlabel('Cell-cycle phase at circadian peak')
plt.savefig('../Results/TestCoupling/'+cell+'_'\
+str(temperature)+'_cell_phase_at_peak.pdf')
plt.ylabel('Frequency')
plt.show()
plt.close()
### ASSOCIATE EACH TRACE TO A GIVEN PHASE AT MITOSIS/PEAK ###
d_idx_traces_uniform = {b: [] for b in bins[:-1]}
for (idx, nb_cc) in l_nb_cc:
for i in range(nb_cc - 1):
for b1, b2 in zip(bins[:-1], bins[1:]):
c1 = ll_phase[idx][ll_idx[idx][i]] >= b1
c2 = ll_phase[idx][ll_idx[idx][i]] < b2
if c1 and c2:
d_idx_traces_uniform[b1].append((idx, i))
break
### COMPUTE DISTRIBUTION OF PERIODS DEPENDING ON THE INITIAL PHASE ###
l_mean = []
l_std = []
for b, l_idx_to_keep in d_idx_traces_uniform.items():
l_period = []
for idx, i in l_idx_to_keep:
l_period.append((ll_idx[idx][i + 1] - ll_idx[idx][i]) / 2)
l_mean.append(np.mean(l_period))
l_std.append(np.std(l_period))
objects = [
str(((b1 + b2) / 2) / (2 * np.pi))[:3]
for b1, b2 in zip(bins[:-1], bins[1:])
]
y_pos = range(len(objects)) #np.linspace(0,3,(len(objects)))
plt.bar(y_pos, l_mean, yerr=l_std, color='steelblue', alpha=0.5)
plt.xticks(y_pos, objects)
if test == 'cycle':
plt.ylabel('Cell-cycle period')
plt.xlabel('Circadian phase at mitosis')
plt.savefig('../Results/TestCoupling/'+cell+'_'+str(temperature)\
+'_Period_cycle_distribution_depending_on_circadian_phase.pdf')
else:
plt.ylabel('Circadian period')
plt.xlabel('Cell-cycle phase at previous circadian peak')
plt.savefig('../Results/TestCoupling/'+cell+'_'+str(temperature)\
+'_Period_clock_distribution_depending_on_cycle_phase.pdf')
plt.show()
plt.close()
def test_sigma_theta(cell='NIH3T3',
temperature=37,
nb_traces=500,
size_block=100):
"""
Compute how the diffusion coefficient (inferred) evolves with the phase.
Parameters
----------
cell : string
Cell condition.
temperature : integer
Temperature condition.
nb_traces : integer
How many traces to run the experiment on.
size_block : integer
Size of the traces chunks (to save memory).
"""
##################### LOAD OPTIMIZED PARAMETERS ##################
path = '../Parameters/Real/opt_parameters_div_'+str(temperature)+"_"\
+cell+'.p'
with open(path, 'rb') as f:
l_parameters = [
dt, sigma_em_circadian, W, pi, N_theta, std_theta, period_theta,
l_boundaries_theta, w_theta, N_phi, std_phi, period_phi,
l_boundaries_phi, w_phi, N_amplitude_theta, mu_amplitude_theta,
std_amplitude_theta, gamma_amplitude_theta,
l_boundaries_amplitude_theta, N_background_theta,
mu_background_theta, std_background_theta, gamma_background_theta,
l_boundaries_background_theta, F
] = pickle.load(f)
##################### DISPLAY PARAMETERS ##################
display_parameters_from_file(path, show=False)
##################### LOAD DATA ##################
if cell == 'NIH3T3':
path = "../Data/NIH3T3.ALL.2017-04-04/ALL_TRACES_INFORMATION.p"
else:
path = "../Data/U2OS-2017-03-20/ALL_TRACES_INFORMATION_march_2017.p"
dataClass = LoadData(path,
nb_traces,
temperature=None,
division=True,
several_cell_cycles=False,
remove_odd_traces=True)
(ll_area_tot_flat, ll_signal_tot_flat, ll_nan_circadian_factor_tot_flat,
ll_obs_phi_tot_flat, T_theta, T_phi) = dataClass.load()
print(len(ll_signal_tot_flat), " traces kept")
##################### SPECIFY F OPTIMIZATION CONDITIONS ##################
#makes algorithm go faster
only_F_and_pi = True
##################### CREATE HIDDEN VARIABLES ##################
theta_var_coupled, amplitude_var, background_var \
= create_hidden_variables(l_parameters = l_parameters)
##################### CREATE BLOCK OF TRACES ##################
ll_area_tot = []
ll_signal_tot = []
ll_nan_circadian_factor_tot = []
ll_obs_phi_tot = []
first = True
zp = enumerate(
zip(ll_area_tot_flat, ll_signal_tot_flat,
ll_nan_circadian_factor_tot_flat, ll_obs_phi_tot_flat))
for index, (l_area, l_signal, l_nan_circadian_factor, l_obs_phi) in zp:
if index % size_block == 0:
if not first:
ll_area_tot.append(ll_area)
ll_signal_tot.append(ll_signal)
ll_nan_circadian_factor_tot.append(ll_nan_circadian_factor)
ll_obs_phi_tot.append(ll_obs_phi)
else:
first = False
ll_area = [l_area]
ll_signal = [l_signal]
ll_nan_circadian_factor = [l_nan_circadian_factor]
ll_obs_phi = [l_obs_phi]
else:
ll_area.append(l_area)
ll_signal.append(l_signal)
ll_nan_circadian_factor.append(l_nan_circadian_factor)
ll_obs_phi.append(l_obs_phi)
#get remaining trace
ll_area_tot.append(ll_area)
ll_signal_tot.append(ll_signal)
ll_nan_circadian_factor_tot.append(ll_nan_circadian_factor)
ll_obs_phi_tot.append(ll_obs_phi)
##################### OPTIMIZATION ##################
l_jP_phase = []
l_jP_amplitude = []
l_jP_background = []
l_gamma = []
l_gamma_0 = []
l_logP = []
ll_signal_hmm = []
ll_idx_phi_hmm = []
ll_nan_circadian_factor_hmm = []
for ll_signal, ll_obs_phi, ll_nan_circadian_factor in zip(
ll_signal_tot, ll_obs_phi_tot, ll_nan_circadian_factor_tot):
### INITIALIZE AND RUN HMM ###
l_var = [theta_var_coupled, amplitude_var, background_var]
hmm = HMM_SemiCoupled(l_var,
ll_signal,
sigma_em_circadian,
ll_val_phi=ll_obs_phi,
waveform=W,
ll_nan_factor=ll_nan_circadian_factor,
pi=pi,
crop=True)
(l_gamma_0_temp, l_gamma_temp, l_logP_temp, ll_alpha, ll_beta, l_E,
ll_cnorm, ll_idx_phi_hmm_temp, ll_signal_hmm_temp,
ll_nan_circadian_factor_hmm_temp) = hmm.run_em()
#crop and create ll_mat_TR
ll_signal_hmm_cropped_temp =[[s for s, idx in zip(l_s, l_idx) if idx>-1]\
for l_s, l_idx in zip(ll_signal_hmm_temp ,ll_idx_phi_hmm_temp)]
ll_idx_phi_hmm_cropped_temp = [ [idx for idx in l_idx if idx>-1] \
for l_idx in ll_idx_phi_hmm_temp ]
ll_mat_TR = [np.array( [theta_var_coupled.TR[:,idx_phi,:] for idx_phi \
in l_idx_obs_phi]) for l_idx_obs_phi in ll_idx_phi_hmm_cropped_temp]
### PLOT TRACE EXAMPLE ###
zp = zip(enumerate(ll_signal_hmm_cropped_temp), l_gamma_temp,
l_logP_temp)
for (idx, signal), gamma, logP in zp:
plt_result = PlotResults(gamma,
l_var,
signal_model,
signal,
waveform=W,
logP=None,
temperature=temperature,
cell=cell)
plt_result.plotEverythingEsperance(False, idx)
if idx == 0:
break
l_jP_phase_temp, l_jP_amplitude_temp,l_jP_background_temp \
= EM.compute_jP_by_block(ll_alpha, l_E, ll_beta, ll_mat_TR,
amplitude_var.TR, background_var.TR,
N_theta, N_amplitude_theta,
N_background_theta, only_F_and_pi)
l_jP_phase.extend(l_jP_phase_temp)
l_jP_amplitude.extend(l_jP_amplitude_temp)
l_jP_background.extend(l_jP_background_temp)
l_gamma.extend(l_gamma_temp)
l_logP.extend(l_logP_temp)
l_gamma_0.extend(l_gamma_0_temp)
ll_signal_hmm.extend(ll_signal_hmm_temp)
ll_idx_phi_hmm.extend(ll_idx_phi_hmm_temp)
ll_nan_circadian_factor_hmm.extend(ll_nan_circadian_factor_hmm_temp)
##################### COMPUTE SIGMA(THETA) ##################
l_mean = []
l_std = []
dic_phase = {}
theta_domain = theta_var_coupled.domain
for idx_theta in range(N_theta):
dic_phase[idx_theta] = []
for jP, ll_idx_obs_phi_trace in zip(l_jP_phase, ll_idx_phi_hmm):
for t, jPt in enumerate(jP):
for idx_theta_i, theta_i in enumerate(theta_domain):
norm = np.sum(jPt[idx_theta_i])
if norm == 0:
continue
jPt_i_norm = jPt[idx_theta_i] / norm
theta_dest = theta_i + (
w_theta + F[idx_theta_i, ll_idx_obs_phi_trace[t]]) * dt
var = 0
for idx_theta_k, theta_k in enumerate(theta_domain):
var+= (min( abs( theta_dest - theta_k ),
abs( theta_dest - (theta_k+2*np.pi) ) ,
abs( theta_dest - (theta_k-2*np.pi) ) )**2) \
*jPt_i_norm[idx_theta_k]
dic_phase[idx_theta_i].append((var, norm))
for idx_theta in range(N_theta):
p_theta = np.sum([tupl[1] for tupl in dic_phase[idx_theta]])
sigma_theta = np.sum( [ (p_theta_t * sigma_theta_t)/p_theta \
for (p_theta_t, sigma_theta_t) in dic_phase[idx_theta] ])
var_sigma_theta = np.sum( [ (sigma_theta_t-sigma_theta)**2*p_theta_t \
/p_theta \
for (p_theta_t, sigma_theta_t) in dic_phase[idx_theta] ])
l_mean.append(sigma_theta)
l_std.append(var_sigma_theta**0.5)
plt.errorbar(theta_domain / (2 * np.pi), l_mean, yerr=l_std, fmt='o')
plt.xlabel(r"Circadian phase $\theta$")
plt.ylabel(r"Phase diffusion SD[$\theta$]")
plt.tight_layout()
plt.savefig('../Results/Correlation/Diffusion_'+cell+'_'\
+str(temperature)+'.pdf')
plt.show()
plt.close()
F_phase = np.angle(np.fft.fftshift(F_t))
F_t = np.fft.fftshift(F_t)
tenth = np.percentile(F_mag.flatten(), 99.2)
ll_idx_coef = [(i, j) for i in range(F_mag.shape[0])
for j in range(F_mag.shape[1]) if F_mag[i, j] < tenth]
print("remaining coef:", F_mag.shape[0] * F_mag.shape[1] - len(ll_idx_coef))
for (i, j) in ll_idx_coef:
F_t[i, j] = 0
F_mag[i, j] = 0
F_phase[i, j] = 0
Fp = np.fft.irfft2(np.fft.ifftshift(F_t))
"""""" """""" """""" """ CREATE HIDDEN VARIABLES """ """""" """""" """"""
theta_var_coupled, amplitude_var, background_var = create_hidden_variables(
l_parameters=l_parameters)
l_var = [theta_var_coupled, amplitude_var, background_var]
domain_theta = theta_var_coupled.domain
domain_phi = theta_var_coupled.codomain
"""""" """""" """""" """ SIMULATE TRACES """ """""" """""" """"""
sim = HMMsim(l_var,
signal_model,
sigma_em_circadian,
waveform=W,
dt=0.5 * dt,
uniform=True)
ll_t_l_xi, ll_t_obs = sim.simulate_n_traces(nb_traces=N_trajectories, tf=100)
"""""" """""" """""" """ REORDER VARIABLES """ """""" """""" ""
ll_obs_circadian = []
ll_obs_nucleus = []
lll_xi_circadian = []
def test_gamma(cell = 'NIH3T3', temperature = 37, nb_trace = 500,
size_block = 100, nb_iter = 15):
##################### LOAD COLORMAP ##################
c = mcolors.ColorConverter().to_rgb
bwr = ( [c('blue'), c('white'), 0.48, c('white'),
0.52,c('white'), c('red')])
### GUESS OR ESTIMATE PARAMETERS ON NON-DIVIDING TRACES ###
wd = os.getcwd()[:-21]
os.chdir(wd)
#remove potential previous results
path = 'Parameters/Real/init_parameters_nodiv_'+str(temperature)\
+"_"+cell+".p"
if os.path.isfile(path) :
os.remove(path)
#run script
print("1_wrap_initial_parameters launched")
os.system("python 1_wrap_initial_parameters.py " + cell + " "\
+ str(temperature) + \
' > TextOutputs/1_wrap_initial_parameters_'+cell\
+'_'+str(temperature)+'.txt')
#check if final result has been created
if os.path.isfile(path) :
print("Initial set of parameters successfully created")
else:
print("BUG, initial set of parameters not created")
for gamma_reg in [0.001, 0.005, 0.01, 0.05, 0.1, 0.5, 1]:
print("gamma =", gamma_reg, " started ")
### REPLACE GAMMA AND STD OU AND RECORD AS OPTIMIZED PARAMETERS NODIV###
gamma_A = gamma_reg
gamma_B = gamma_reg
mu_A, std_A, mu_B, std_B = estimate_OU_par(cell, temperature, \
gamma_A = gamma_A, gamma_B = gamma_B)
path = 'Parameters/Real/init_parameters_nodiv_'+str(temperature)\
+"_"+cell+".p"
with open(path, 'rb') as f:
[dt, sigma_em_circadian, W, pi,
N_theta, std_theta, period_theta, l_boundaries_theta, w_theta,
N_phi, std_phi, period_phi, l_boundaries_phi, w_phi,
N_amplitude_theta, mu_amplitude_theta, std_amplitude_theta,
gamma_amplitude_theta, l_boundaries_amplitude_theta,
N_background_theta, mu_background_theta, std_background_theta,
gamma_background_theta, l_boundaries_background_theta,
F] = pickle.load(f)
gamma_amplitude_theta = gamma_A
gamma_background_theta = gamma_B
std_amplitude_theta = std_A
std_background_theta = std_B
l_parameters = [dt, sigma_em_circadian, W, pi,
N_theta, std_theta, period_theta, l_boundaries_theta, w_theta,
N_phi, std_phi, period_phi, l_boundaries_phi, w_phi,
N_amplitude_theta, mu_amplitude_theta, std_amplitude_theta,
gamma_amplitude_theta, l_boundaries_amplitude_theta,
N_background_theta, mu_background_theta, std_background_theta,
gamma_background_theta, l_boundaries_background_theta,
F]
##################### WRAP PARAMETERS ##################
path = "Parameters/Real/opt_parameters_nodiv_"+str(temperature)\
+"_"+cell+".p"
pickle.dump( l_parameters, open( path, "wb" ) )
### COMPUTE WAVEFORM BIAS ###
#remove potential previous results
path = "Parameters/Misc/F_no_coupling_"+str(temperature)+"_"+cell+'.p'
if os.path.isfile(path) :
os.remove(path)
#run script
print("7_bias launched")
os.system("python 7_validate_inference_dividing.py " + str(nb_iter) \
+ " "+ str(nb_trace) + " "+ str(size_block) + " "+cell \
+ " "+ str(temperature) + " True"+ ' > TextOutputs/7_bias_'\
+cell+'_'+str(temperature)+'.txt')
#check if final result has been created
if os.path.isfile(path) :
print("Bias successfully computed")
else:
print("BUG, bias not computed")
### OPTIMIZE COUPLING ON DIVIDING TRACES ###
#remove potential previous results
path = "Parameters/Real/opt_parameters_div_"+str(temperature)+"_"\
+cell+".p"
if os.path.isfile(path) :
os.remove(path)
#run script
print("4_optimize_parameters_dividing launched")
os.system("python 4_optimize_parameters_dividing.py " + str(nb_iter) \
+ " "+ str(nb_trace) + " "+ str(size_block) + " "+cell \
+ " "+ str(temperature)\
+ ' > TextOutputs/4_optimize_parameters_dividing_'+cell\
+'_'+str(temperature)+'.txt')
#check if final result has been created
if os.path.isfile(path) :
print("Optimized set of parameters on dividing traces"\
+" successfully created")
else:
print("BUG, optimized set of parameters on"\
+" dividing traces not created")
### COMPLUTE/PLOT COUPLING AND PHASE DENSITY ###
##################### LOAD OPTIMIZED PARAMETERS ##################
path = 'Parameters/Real/opt_parameters_div_'+str(temperature)\
+"_"+cell+'.p'
with open(path, 'rb') as f:
l_parameters = [dt, sigma_em_circadian, W, pi,
N_theta, std_theta, period_theta, l_boundaries_theta, w_theta,
N_phi, std_phi, period_phi, l_boundaries_phi, w_phi,
N_amplitude_theta, mu_amplitude_theta, std_amplitude_theta,
gamma_amplitude_theta, l_boundaries_amplitude_theta,
N_background_theta, mu_background_theta, std_background_theta,
gamma_background_theta, l_boundaries_background_theta,
F] = pickle.load(f)
period = None
##################### LOAD DATA ##################
if cell == 'NIH3T3':
path = "Data/NIH3T3.ALL.2017-04-04/ALL_TRACES_INFORMATION.p"
else:
path = "Data/U2OS-2017-03-20/ALL_TRACES_INFORMATION_march_2017.p"
dataClass=LoadData(path, nb_trace, temperature = temperature,
division = True, several_cell_cycles = False,
remove_odd_traces = True)
if period is None:
(ll_area, ll_signal, ll_nan_circadian_factor, ll_obs_phi, ll_peak,
ll_idx_cell_cycle_start, T_theta, T_phi) \
= dataClass.load(period_phi = period, load_annotation = True)
else:
(ll_area, ll_signal, ll_nan_circadian_factor, ll_obs_phi, ll_peak,
ll_idx_cell_cycle_start, T_theta, std_T_theta, T_phi, std_T_phi) \
= dataClass.load(period_phi = period, load_annotation = True)
ll_idx_peak = [[idx for idx, v in enumerate(l_peak) if v>0] for \
l_peak in ll_peak]
print(len(ll_signal), " traces kept")
##################### CREATE HIDDEN VARIABLES ##################
theta_var_coupled, amplitude_var, background_var = \
create_hidden_variables(l_parameters = l_parameters)
l_var = [theta_var_coupled, amplitude_var, background_var]
##################### CREATE AND RUN HMM ##################
hmm=HMM_SemiCoupled(l_var, ll_signal, sigma_em_circadian, ll_obs_phi,
waveform = W,
ll_nan_factor = ll_nan_circadian_factor,
pi = pi, crop = True )
l_gamma_div, l_logP_div = hmm.run(project = False)
##################### REMOVE BAD TRACES #####################
Plim = np.percentile(l_logP_div, 10)
idx_to_keep = [i for i, logP in enumerate(l_logP_div) if logP>Plim ]
l_gamma_div = [l_gamma_div[i] for i in idx_to_keep]
ll_signal = [ll_signal[i] for i in idx_to_keep]
ll_area = [ll_area[i] for i in idx_to_keep]
l_logP_div = [l_logP_div[i] for i in idx_to_keep]
ll_obs_phi = [ll_obs_phi[i] for i in idx_to_keep]
ll_idx_cell_cycle_start = [ll_idx_cell_cycle_start[i] \
for i in idx_to_keep]
ll_idx_peak = [ll_idx_peak[i] for i in idx_to_keep]
print("Kept traces with div: ", len(idx_to_keep))
##################### CROP SIGNALS FOR PLOTTING ##################
l_first = [[it for it, obj in enumerate(l_obs_phi) \
if obj!=-1][0] for l_obs_phi in ll_obs_phi]
l_last = [[len(l_obs_phi)-it-1 for it, obj \
in enumerate(l_obs_phi[::-1]) if obj!=-1][0] \
for l_obs_phi in ll_obs_phi]
ll_signal = [l_signal[first:last+1] for l_signal, first, last \
in zip(ll_signal, l_first, l_last)]
ll_area = [l_area[first:last+1] for l_area, first, last \
in zip(ll_area, l_first, l_last)]
ll_obs_phi = [l_obs_phi[first:last+1] for l_obs_phi, first, last \
in zip(ll_obs_phi, l_first, l_last)]
ll_idx_cell_cycle_start = [ [v for v in l_idx_cell_cycle_start \
if v>=first and v<=last ] for l_idx_cell_cycle_start, first, last \
in zip(ll_idx_cell_cycle_start, l_first, l_last)]
ll_idx_peak = [ [v for v in l_idx_peak if v>=first and v<=last ] \
for l_idx_peak, first, last in zip(ll_idx_peak, l_first, l_last)]
##################### CREATE ll_idx_obs_phi and ll_val_phi###############
ll_idx_obs_phi = []
for l_obs in ll_obs_phi:
l_idx_obs_phi = []
for obs in l_obs:
l_idx_obs_phi.append( int(round(obs/(2*np.pi) *\
len(theta_var_coupled.codomain )))\
%len(theta_var_coupled.codomain ) )
ll_idx_obs_phi.append(l_idx_obs_phi)
##################### PLOT FITS ##################
zp = zip(enumerate(ll_signal),l_gamma_div, l_logP_div, ll_area,
ll_obs_phi, ll_idx_cell_cycle_start, ll_idx_peak)
for ((idx, signal), gamma, logP, area, l_obs_phi,
l_idx_cell_cycle_start, l_idx_peak) in zp:
plt_result = PlotResults(gamma, l_var, signal_model, signal,
waveform = W, logP = logP,
temperature = temperature, cell = cell)
E_model, E_theta, E_A, E_B = \
plt_result.plotEverythingEsperance( True, idx)
##################### PLOT COUPLING AND PHASE SPACE DENSITY ############
#plot phase density
plot_phase_space_density(l_var, l_gamma_div, ll_idx_obs_phi,
F_superimpose = F, save = True, cmap = bwr,
temperature = temperature, cell = cell,
period = gamma_reg,
folder = 'Results/TestGamma' )
#plot coupling
plt.imshow(F.T, cmap=bwr, vmin=-0.3, vmax=0.3,
interpolation='nearest', origin='lower',
extent=[0, 2*np.pi,0, 2*np.pi])
plt.colorbar()
plt.xlabel(r'$\theta$')
plt.ylabel(r'$\phi$')
plt.title('Coupling Function')
plt.savefig("Results/TestGamma/Coupling_"+str(temperature)+"_"\
+cell+'_'+str(gamma_reg)+'.pdf')
plt.close()
