In [1]:
# PyABC imports
from pyabc import (ABCSMC, Distribution, RV,
History, MedianEpsilon)
from pyabc.populationstrategy import ConstantPopulationSize, AdaptivePopulationSize
from pyabc.epsilon import MedianEpsilon
from pyabc.sampler import MulticoreEvalParallelSampler
In [2]:
# Custom imports
from ionchannelABC import (ion_channel_sum_stats_calculator,
IonChannelAcceptor,
IonChannelDistance,
EfficientMultivariateNormalTransition,
plot_parameter_sensitivity,
plot_parameters_kde,
plot_sim_results,
plot_distance_weights)
In [3]:
# Other necessary imports
import numpy as np
import subprocess
import pandas as pd
import io
import os
import tempfile
In [4]:
# Plotting imports
import seaborn as sns
import matplotlib.pyplot as plt
%matplotlib inline
%config Inline.Backend.figure_format = 'retina'
In [5]:
from channels.ikr import ikr as model
#model.sample({})
In [6]:
measurements = model.get_experiment_data()
obs = measurements.to_dict()['y']
exp = measurements.to_dict()['exp']
errs = measurements.to_dict()['errs']
In [7]:
limits = dict(g_Kr=(0, 1),
p1=(0, 1),
p2=(0, 1),
p3=(0, 1),
p4=(0, 1),
p5=(-1, 1),
p6=(-1, 1),
q1=(0, 1),
q2=(-1, 1),
q3=(0, 1.0),
q4=(-0.5, 0.5),
q5=(0, 0.01),
q6=(-0.1, 0),
k_f=(0, 1.0),
k_b=(0, 1.0))
prior = Distribution(**{key: RV("uniform", a, b - a)
for key, (a,b) in limits.items()})
In [9]:
parameters = ['ikr.'+k for k in limits.keys()]
In [10]:
distance_fn=IonChannelDistance(
obs=obs,
exp_map=exp,
err_bars=errs,
err_th=0.1)
In [11]:
sns.set_context('talk')
g = plot_distance_weights(model, distance_fn)
In [12]:
g.savefig('results/ikr/dist_weights.pdf')
In [14]:
grid1, grid2 = plot_parameter_sensitivity(
model,
parameters,
distance_fn,
sigma=0.1,
n_samples=1000,
plot_cutoff=0.05)
In [15]:
grid1.savefig('results/ikr/sensitivity.pdf')
grid2.savefig('results/ikr/sensitivity_fit.pdf')
In [16]:
limits = dict(g_Kr=(0, 1),
p3=(0, 1),
p4=(0, 1),
p5=(-1, 1),
p6=(-1, 1),
q3=(0, 1.0),
q4=(-0.5, 0.5),
q5=(0, 0.01),
q6=(-0.1, 0),
k_f=(0, 1.0),
k_b=(0, 1.0))
prior = Distribution(**{key: RV("uniform", a, b - a)
for key, (a,b) in limits.items()})
In [17]:
db_path = ('sqlite:///' +
os.path.join(tempfile.gettempdir(), "hl-1_ikr.db"))
print(db_path)
In [18]:
# Let's log all the sh!t
import logging
logging.basicConfig()
abc_logger = logging.getLogger('ABC')
abc_logger.setLevel(logging.DEBUG)
eps_logger = logging.getLogger('Epsilon')
eps_logger.setLevel(logging.DEBUG)
In [19]:
abc = ABCSMC(models=model,
parameter_priors=prior,
distance_function=IonChannelDistance(
obs=obs,
exp_map=exp,
err_bars=errs,
err_th=0.1),
population_size=AdaptivePopulationSize(
start_nr_particles=5000,
mean_cv=0.4,
max_population_size=5000,
min_population_size=2500),
summary_statistics=ion_channel_sum_stats_calculator,
transitions=EfficientMultivariateNormalTransition(),
eps=MedianEpsilon(),
sampler=MulticoreEvalParallelSampler(n_procs=12),
acceptor=IonChannelAcceptor())
In [20]:
abc_id = abc.new(db_path, obs)
In [33]:
history = abc.run(minimum_epsilon=0.05, max_nr_populations=10, min_acceptance_rate=0.005)
In [69]:
db_path = 'sqlite:////scratch/cph211/tmp/hl-1_ikr.db'
history = History(db_path)
history.all_runs()
Out[69]:
In [70]:
history.id = 5
In [34]:
sns.set_context('talk')
evolution = history.get_all_populations()
grid = sns.relplot(x='t', y='epsilon', size='samples', data=evolution[evolution.t>=0])
grid.savefig('results/ikr/eps_evolution.pdf')
In [35]:
df, w = history.get_distribution(m=0)
In [43]:
g = plot_parameters_kde(df, w, limits, aspect=5, height=1.1)
In [44]:
g.savefig('results/ikr/parameters_kde.pdf')
In [37]:
# Generate parameter samples
n_samples = 100
df, w = history.get_distribution(m=0)
th_samples = df.sample(n=n_samples, weights=w, replace=True).to_dict(orient='records')
In [38]:
# Generate sim results samples
samples = pd.DataFrame({})
for i, th in enumerate(th_samples):
output = model.sample(pars=th, n_x=50)
output['sample'] = i
output['distribution'] = 'post'
samples = samples.append(output, ignore_index=True)
In [40]:
from ionchannelABC import plot_sim_results
sns.set_context('talk')
g = plot_sim_results(samples, obs=measurements)
# Set axis labels
xlabels = ["voltage, mV", "voltage, mV", "voltage, mV", "time, ms"]
ylabels = ["current density, pA/pF", "activation", "inactivation"]
for ax, xl in zip(g.axes.flatten(), xlabels):
ax.set_xlabel(xl)
for ax, yl in zip(g.axes.flatten(), ylabels):
ax.set_ylabel(yl)
In [41]:
g.savefig('results/ikr/ikr_sim_results.pdf')
In [45]:
# Activation fit to Boltzmann equation
from scipy.optimize import curve_fit
grouped = samples[samples['exp']==1].groupby('sample')
def fit_boltzmann(group):
def boltzmann(V, Vhalf, K):
return 1/(1+np.exp((Vhalf-V)/K))
guess = (-30, 10)
popt, _ = curve_fit(boltzmann, group.x, group.y)
return popt
output = grouped.apply(fit_boltzmann).apply(pd.Series)
In [47]:
import scipy.stats as st
Vhalf = output[0].tolist()
rv = st.rv_discrete(values=(Vhalf, [1/len(Vhalf),]*len(Vhalf)))
print("median: {}".format(rv.median()))
print("95% CI: {}".format(rv.interval(0.95)))
In [49]:
slope = output[1].tolist()
rv = st.rv_discrete(values=(slope, [1/len(slope),]*len(slope)))
print("median: {}".format(rv.median()))
print("95% CI: {}".format(rv.interval(0.95)))
In [54]:
# Inactivation fit to Boltzmann equation
from scipy.optimize import curve_fit
grouped = samples[samples['exp']==2].groupby('sample')
def fit_boltzmann(group):
def boltzmann(V, Vhalf, K):
return 1-1/(1+np.exp((Vhalf-V)/K))
guess = (-40, 30)
popt, _ = curve_fit(boltzmann, group.x, group.y)
return popt
output = grouped.apply(fit_boltzmann).apply(pd.Series)
In [58]:
Vhalf = output[0].tolist()
rv = st.rv_discrete(values=(Vhalf, [1/len(Vhalf),]*len(Vhalf)))
print("median: {}".format(rv.median()))
print("95% CI: {}".format(rv.interval(0.95)))
In [59]:
slope = output[1].tolist()
rv = st.rv_discrete(values=(slope, [1/len(slope),]*len(slope)))
print("median: {}".format(rv.median()))
print("95% CI: {}".format(rv.interval(0.95)))
In [ ]: