- Author:
- Shelley Fong <s.fong@auckland.ac.nz>
- Date:
- 2021-12-06 08:25:06+13:00
- Desc:
- Adding units submodule manually
- Permanent Source URI:
- https://staging.physiomeproject.org/workspace/705/rawfile/9f1753b7ba6c67dc1d2964813a1ed5f3322a73ce/parameter_finder/find_BG_parameters_composite.py
# find bond-graph parameters for a system with multiple modules
# require separate folders within this directory containing each module's kinetic_parameters.py file and data files
# write out cellml file in text form
# prints out error between given kinetic parameters, and parameters found back-transforming the bond-graph parameters
import os
import sys
import importlib
import json
import csv
import math
import numpy as np
from scipy.linalg import null_space
import sympy
from sympy import Matrix, S, nsimplify
from fractions import Fraction
def read_IDs(path):
data = []
with open(path,'r') as f:
reader = csv.reader(f)
for row in reader:
data.append(row[0])
f.close()
return data
def load_matrix(stoich_path):
matrix = []
with open(stoich_path,'r') as f:
reader = csv.reader(f,delimiter=',')
for row in reader:
matrix.append([int(r) for r in row])
f.close()
return matrix
# def rational_nullspace(A, max_denom = 10):
# v = null_space(A)
# vFrac = [[Fraction(num).limit_denominator(max_denominator=max_denom) for num in row] for row in v]
# vRat = [] #np.zeros([len(vFrac),len(vFrac[0])])
# if not v.any():
# return []
# for row in vFrac:
# largest_denom = max([res.denominator for res in row])
# vRat.append( [vi.numerator for vi in row] )
# return vRat
def calcT(I_vec,num_rows):
num_cols = len(I_vec)
T = np.zeros([num_rows,num_cols])
for i in range(num_cols):
T[I_vec[i]][i] = 1
return T
if __name__ == "__main__":
# Set directories
current_dir = os.getcwd()
main_dir = os.path.dirname(current_dir)
output_dir = current_dir + '\output'
whole_name = main_dir.split('\\')[-1]
if not os.path.exists(output_dir):
os.mkdir(output_dir)
## Define volumes (unit pL)
V_myo = 34.4
V_e = 5.182 # external volume
V_SR = V_myo*0.035 # SR volume
V_di = V_myo*0.0539 # diadic volume
V = dict()
V['V_myo'] = V_myo
V['V_SR'] = V_SR
V['V_di'] = V_di
V['V_e'] = V_e
## Load stoichiometric matrices and kinetic rate constants
subsystem_names = ['cAMP','GPCR_B1AR_reduced','GPCR_M2_reduced']
# subsystem_names = ['cAMP','GsProtein','LRGbinding_B1AR','GiProtein','LRGbinding_M2'] #['cAMP', 'LRGbinding_B1AR', 'B1AR', 'PKA', 'PLB', 'Inhib1', 'GsProtein']
num_subsystems = len(subsystem_names)
sys_struct = {c:{} for c in subsystem_names}
rxnIDs = []
Knames = []
Kname_modules = dict()
for i_system in range(num_subsystems):
sys_name = subsystem_names[i_system]
sys_dir = main_dir + '\\' + sys_name +'\parameter_finder\\'
os.chdir(sys_dir)
forward_mat_path = 'data\\all_forward_matrix.txt'
reverse_mat_path = 'data\\all_reverse_matrix.txt'
N_f = load_matrix(forward_mat_path)
N_r = load_matrix(reverse_mat_path)
sys_struct[sys_name]['N_f'] = N_f
sys_struct[sys_name]['N_r'] = N_r
# print(subsystem_names[i_system])
dims = dict()
dims['num_rows'] = len(N_f)
dims['num_cols'] = len(N_f[0])
I = np.identity(dims['num_cols'])
M = np.append(np.append(I, np.transpose(N_f),1), np.append(I, np.transpose(N_r),1),0)
sys.path.append(sys_dir)
globals()['kp_' + sys_name] = importlib.import_module('kinetic_parameters_' + sys_name)
[k_kinetic, N_cT, K_C, W] = globals()['kp_' + sys_name].kinetic_parameters(M, True, dims, V)
sys_struct[sys_name]['kfkr'] = k_kinetic
# the below Kc and NcT are not used in this composite model:
sys_struct[sys_name]['Kc'] = K_C
sys_struct[sys_name]['N_cT'] = N_cT
rxnID = read_IDs('data\\rxnID.txt')
rxnIDs.extend(rxnID)
sys_struct[sys_name]['rxnID'] = rxnID
Kname = read_IDs('data\\Kname.txt')
Knames.extend(Kname)
sys_struct[sys_name]['Kname'] = Kname
Kunique = []
for ik in Knames:
# if ~any(strcmp(Kunique,ik)):
if ik not in Kunique:
Kunique.append(ik)
os.chdir(current_dir)
# relations between submodule to whole module
for name in subsystem_names:
ids = [Kunique.index(kid) for kid in sys_struct[name]['Kname']]
sys_struct[name]['I_vec'] = ids
num_rows = max(sys_struct[subsystem_names[-1]]['I_vec'])+1
N_f = []
N_r = []
for sys_name in subsystem_names:
# print(sys_name)
T = calcT(sys_struct[sys_name]['I_vec'],num_rows)
sys_struct[sys_name]['T'] = T
new_f = np.matmul(T,sys_struct[sys_name]['N_f'])
new_r = np.matmul(T,sys_struct[sys_name]['N_r'])
if not len(N_f):
N_f = new_f
N_r = new_r
else:
N_f = np.append(N_f, new_f,1)
N_r = np.append(N_r, new_r,1)
N_fT = np.transpose(N_f)
N_rT = np.transpose(N_r)
N = N_r - N_f
N_T = N_rT - N_fT
num_cols = len(N[0])
I = np.identity(num_cols)
M = np.append(np.append(I, N_fT,1), np.append(I, N_rT,1),0)
M_rref = sympy.Matrix(M).rref()
## Set up the vectors for kinetic rate constants
kf = []
kr = []
for sys_name in subsystem_names:
nrx = int(len(sys_struct[sys_name]['kfkr'])/2)
kf.extend(sys_struct[sys_name]['kfkr'][:nrx])
kr.extend(sys_struct[sys_name]['kfkr'][nrx:])
k_kinetic = kf +kr
W = list(np.append([1]*len(N[0]), [V_myo]*num_rows))
lambda_expo = np.matmul(np.linalg.pinv(M), [math.log(k) for k in k_kinetic])
lambdaW = [math.exp(l) for l in lambda_expo]
lambdak = [lambdaW[i]/W[i] for i in range(len(W))]
kappa = lambdak[:len(N[0])]
K = lambdak[len(N[0]):]
file = open(output_dir + '/all_parameters_out.json', 'w')
data = { "K": K, "kappa": kappa, "k_kinetic": k_kinetic }
json.dump(data, file)
# Checks
N_rref = sympy.Matrix(N).rref()
R = nsimplify(Matrix(N), rational=True).nullspace() #rational_nullspace(N, max_denom=len(N[0]))
if R:
R = np.transpose(np.array(R).astype(np.float64))[0]
# Check that there is a detailed balance constraint
Z = nsimplify(Matrix(M), rational=True).nullspace() #rational_nullspace(M, 2)
if Z:
Z = np.transpose(np.array(Z).astype(np.float64))[0]
k_est = np.matmul(M,[math.log(k) for k in lambdaW])
k_est = [math.exp(k) for k in k_est]
diff = [(k_kinetic[i] - k_est[i])/k_kinetic[i] for i in range(len(k_kinetic))]
error = np.sum([abs(d) for d in diff])
K_eq = [kf[i]/kr[i] for i in range(len(kr))]
try:
zero_est = np.matmul(np.transpose(R),K_eq)
zero_est_log = np.matmul(np.transpose(R),[math.log(k) for k in K_eq])
except:
print('undefined R nullspace')
# ### print outputs ###
for ik in range(len(kappa)):
print('var kappa_%s: fmol_per_sec {init: %g, pub: out};' %(rxnIDs[ik],kappa[ik]))
for ik in range(len(Kunique)):
print('var K_%s: per_fmol {init: %g, pub: out};' %(Kunique[ik],K[ik]))
print('error = ', error)
# initialise struct for storing modules contributing to a given K
for ik in range(len(Kunique)):
Kname_modules[Kunique[ik]] = []
for sys_name in subsystem_names:
modKname = sys_struct[sys_name]['Kname']
for ik in range(len(modKname)):
Kname_modules[modKname[ik]].append(sys_name)
# write out CellML code
if True:
cellmlfilepath = output_dir + '\\TEMP.cellml.txt'
with open(cellmlfilepath, 'w') as cid:
cid.write('def model %s as\n def import using "units_and_constants/units_BG.cellml" for\n\
unit mM using unit mM;\nunit fmol using unit fmol;\nunit per_fmol using unit per_fmol;\n\
unit J_per_mol using unit J_per_mol;\nunit fmol_per_sec using unit fmol_per_sec;\n\
unit C_per_mol using unit C_per_mol;\n unit J_per_C using unit J_per_C;\n\
unit microm3 using unit microm3;\n unit fF using unit fF;\n\
unit fC using unit fC;\n unit fA using unit fA;\n\
unit per_second using unit per_second;\n unit millivolt using unit millivolt;\n\
unit per_sec using unit per_sec;\n unit J_per_K_per_mol using unit J_per_K_per_mol;\n\
unit fmol_per_L using unit fmol_per_L;\n unit fmol_per_L_per_sec using unit fmol_per_L_per_sec;\n\
unit per_sec_per_fmol_per_L using unit per_sec_per_fmol_per_L;\n unit uM using unit uM;\n\
unit mM_per_sec using unit mM_per_sec;\n unit uM_per_sec using unit uM_per_sec;\n\
unit pL using unit pL;\n unit m_to_u using unit m_to_u;\n enddef;\n' %(whole_name))
cid.write('def import using "units_and_constants/constants_BG.cellml" for\n\
comp constants using comp constants;\nenddef;\n\n')
for module in subsystem_names:
cid.write('def import using "%s/BG_%s.cellml" for\ncomp %s using comp %s;\nenddef;\n' % (
module, module, module, module))
cid.write('\ndef comp BG_parameters as\n')
for ik in range(len(kappa)):
cid.write('var kappa_%s: fmol_per_sec {init: %g, pub: out};\n' % (rxnIDs[ik], kappa[ik]))
for ik in range(len(Kunique)):
cid.write('var K_%s: per_fmol {init: %g, pub: out};\n' % (Kunique[ik], K[ik]))
cid.write('enddef;\n')
cid.write(' def comp environment as\n\
var time: second {pub: out};\n\
var vol_myo: pL {init: 34.4, pub: out};\n\
var freq: dimensionless {init: 500};\n\
// stimulus\n\
// ramp UP and ramp DOWN\n\
var stimSt1: second {init: 3.5e-4};\n\
var stimDur1: second {init: 0.25e-4};\n\
var tRamp1: second {init: 1.8e-4};\n\
var stimMag1: fmol {init: 1e1};\n\
var stimHolding1: fmol {init: 1e-5};\n\
var m1: fmol_per_sec;\n\
m1 = stimMag1/tRamp1;\n\
q_LB1_init = sel\n\
case (time < stimSt1) and (time > stimSt1-tRamp1): \n\
stimHolding1+m1*(time-stimSt1+tRamp1);\n\
case (time >= stimSt1) and (time < stimSt1+stimDur1): \n\
stimMag1+stimHolding1;\n\
case (time < stimSt1+tRamp1+stimDur1) and (time >= stimSt1+stimDur1): \n\
stimHolding1+-m1*(time-stimSt1-tRamp1-stimDur1);\n\
otherwise: \n\
stimHolding1;\n\
endsel;\n\
var stimSt2: second {init: 7e-4};\n\
var stimDur2: second {init: 0.25e-4};\n\
var tRamp2: second {init: 1.8e-4};\n\
var stimMag2: fmol {init: 1e1};\n\
var stimHolding2: fmol {init: 1e-5};\n\
var m2: fmol_per_sec;\n\
m2 = stimMag2/tRamp2;\n\
q_LM2_init = sel\n\
case (time < stimSt2) and (time > stimSt2-tRamp2): \n\
stimHolding2+m2*(time-stimSt2+tRamp2);\n\
case (time >= stimSt2) and (time < stimSt2+stimDur2): \n\
stimMag2+stimHolding2;\n\
case (time < stimSt2+tRamp2+stimDur2) and (time >= stimSt2+stimDur2): \n\
stimHolding2+-m2*(time-stimSt2-tRamp2-stimDur2);\n\
otherwise: \n\
stimHolding2;\n\
endsel;\n')
for j in range(len(K)):
cid.write('var q_%s_init: fmol {init: 1e-888};\n' % Kunique[j])
cid.write('\n// mass conservation checks\n')
cid.write(' var LB1_T: fmol;\n\
var RB1_T: fmol;\n\
var Gs_T: fmol;\n\
var adenosine_T: fmol;\n\
LB1_T = q_L_RB1_inactive+q_LB1+q_L_RB1_Gs+q_L_RB1+q_L_RB1_tag+q_L_RB1_GRKArr;\n\
RB1_T = q_RB1_inactive+q_L_RB1_inactive+q_RB1+q_RB1_Gs+q_L_RB1+q_L_RB1_Gs +q_RB1_tag+q_L_RB1_tag+q_RB1_GRKArr+q_L_RB1_GRKArr;\n\
Gs_T = q_Gs+q_RB1_Gs+q_L_RB1_Gs+q_Gsa_GTP+q_Gsa_GDP;\n\
adenosine_T = q_cAMP+q_PDE_cAMP+q_five_AMP+q_ATP+q_AC_ATP+q_Gsa_GTP_AC_ATP+q_FSK_AC_ATP;\n');
cid.write('\n// Global value\n')
for j in range(len(K)):
cid.write('var q_%s: fmol {pub: out};\n' % Kunique[j])
for module in subsystem_names:
modKname = sys_struct[module]['Kname']
cid.write('\n// %s imports\n' % module)
for j in modKname:
cid.write('var q_%s_m%s: fmol {pub: in};\n' % (j, module))
cid.write('\n')
cid.write('\n')
for kun in Kunique:
cid.write('q_%s = q_%s_init' % (kun, kun))
for mod in Kname_modules[kun]:
cid.write(' + q_%s_m%s ' % (kun, mod))
cid.write(';\n')
cid.write('enddef;\n')
cid.write('\n')
for module in subsystem_names:
modKname = sys_struct[module]['Kname']
cid.write('def map between environment and %s for\n' % module)
cid.write('vars time and time;\n')
for mod in modKname:
cid.write('vars q_%s_m%s and q_%s;\n' % (mod, module, mod))
cid.write('vars q_%s and q_%s_global;\n' % (mod, mod))
cid.write('enddef;\n\n')
for module in subsystem_names:
modKname = sys_struct[module]['Kname']
modrxnID = sys_struct[module]['rxnID']
cid.write('def map between BG_parameters and %s for\n' % (module))
for ik in modrxnID:
cid.write('vars kappa_%s and kappa_%s;\n' % (ik, ik))
for mod in modKname:
cid.write('vars K_%s and K_%s;\n' % (mod, mod))
cid.write('enddef;\n')
cid.write('\n')
for module in subsystem_names:
cid.write('def map between constants and %s for\n' % (module))
cid.write('\tvars R and R;\n\tvars T and T;\nenddef;\n')
cid.write('\nenddef;\n')
cid.close()
