- Author:
- Shelley Fong <s.fong@auckland.ac.nz>
- Date:
- 2021-10-27 11:22:54+13:00
- Desc:
- Adding GEF stuff
- Permanent Source URI:
- https://models.cellml.org/workspace/700/rawfile/fcefc10a7dd7e17af448dbb9d7bab2ee8a2746f1/parameter_finder/find_BG_parameters_M2.m
% find bond-graph parameters whole whole cell with multiple modules
% present:
% {'cAMP','LRGbinding_B1AR','LRGbinding_M2','GsProtein','GiProtein'}
% based on Pan cardiac AP 2018 code
% find kf and kr through a single file that accounts for potential closed
% loops in the new composite model
clear;
clc;
close all;
%% Set directories
current_dir = cd;
Idx_backslash = find(current_dir == filesep);
parent_dir = current_dir(1:Idx_backslash(end-1));
main_dir = current_dir(1:Idx_backslash(end));
output_dir = [current_dir filesep 'output' filesep];
%% Define constants
R = 8.314; % unit J/mol/K
T = 310;
F = 96485;
N_A = 6.022e23;
combined_kinetic_parameters = false; % all listed modules must be present
noLRG = false;
%% 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 = struct();
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
if false
% order of modules is not guaranteed
d = dir(main_dir);
isub = [d(:).isdir]; %# returns logical vector
array_names = {d(isub).name}';
array_names(ismember(array_names,{'.','..','.git','MATLAB','units_and_constants'})) = [];
disp('Modules are:');
disp(array_names);
else
array_names = {'LRGbinding_M2','GiProtein'};
end
num_subsystems = length(array_names);
sys_struct = cell(num_subsystems,1);
rxnIDs = {};
Knames = {};
Kname_modules = struct();
for i_system = 1:num_subsystems
sys_name = array_names{i_system};
sys_struct{i_system}.name = sys_name;
sys_dir = [main_dir sys_name '\parameter_finder\'];
cd(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{i_system}.N_f = N_f;
sys_struct{i_system}.N_r = N_r;
% disp(array_names{i_system});
dims = struct();
dims.num_rows = size(N_f,1);
dims.num_cols = size(N_f,2);
I = eye(dims.num_cols);
M = [I transpose(N_f); I transpose(N_r)];
if ~combined_kinetic_parameters
[k_kinetic, N_cT, K_C, W] = kinetic_parameters(M, true, dims, V);
sys_struct{i_system}.kfkr = k_kinetic;
sys_struct{i_system}.Kc = K_C;
sys_struct{i_system}.N_cT = N_cT;
end
% sys_struct{i_system}.W = W(dims.num_cols+1:end);
fID = fopen('data\rxnID.txt', 'r');
rxnID = textscan(fID,'%s', 'delimiter','\n');
fclose(fID);
rxnIDs = [rxnIDs; rxnID{1}];
sys_struct{i_system}.rxnID = rxnID{1};
fID = fopen('data\Kname.txt', 'r');
Kname = textscan(fID,'%s', 'delimiter','\n');
fclose(fID);
Knames = [Knames; Kname{1}];
sys_struct{i_system}.Kname = Kname{1};
end
Kunique = {};
for ik=1:length(Knames)
if ~any(strcmp(Kunique,Knames{ik}))
Kunique = [Kunique; Knames{ik}];
end
end
cd(current_dir)
% relations between submodule to whole module
% {{'LRGbinding_M2','GiProtein'}}
for j = 1:length(array_names)
ids = [];
for id = 1:length(sys_struct{j}.Kname)
ids = [ids, find(strcmp(Kunique, sys_struct{j}.Kname{id}))];
end
sys_struct{j}.I_vec = ids;
end
num_rows = max(sys_struct{size(sys_struct,1)}.I_vec);
N_f = [];
N_r = [];
for i_system = 1:num_subsystems
disp(array_names{i_system});
T = calcT(sys_struct{i_system}.I_vec,num_rows);
sys_struct{i_system}.T = T;
N_f = [N_f T*sys_struct{i_system}.N_f];
N_r = [N_r T*sys_struct{i_system}.N_r];
end
N_fT = transpose(N_f);
N_rT = transpose(N_r);
N = N_r - N_f;
N_T = N_rT - N_fT;
num_cols = size(N,2);
I = eye(num_cols);
M = [I N_fT; I N_rT];
M_rref = rref(M);
%% Set up the vectors for kinetic rate constants
% {'cAMP','LRGbinding_B1AR','LRGbinding_M2','B1AR','GsProtein','GiProtein'}
kf = [];
kr = [];
W = ones(size(N,2),1);
if combined_kinetic_parameters
[k_kinetic, N_cT, K_C, W] = grand_kinetic_parameters(M, true, dims, V, 0);
sys_struct{i_system}.kfkr = k_kinetic;
sys_struct{i_system}.Kc = K_C;
sys_struct{i_system}.N_cT = N_cT;
kf = k_kinetic(1:num_cols);
kr = k_kinetic(num_cols+1:end);
else
for i_system=1:num_subsystems
nrx = length(sys_struct{i_system}.kfkr)/2;
kf = [kf, sys_struct{i_system}.kfkr(1:nrx)'];
kr = [kr, sys_struct{i_system}.kfkr(nrx+1:end)'];
end
k_kinetic = [kf, kr]';
end
W = [ones(size(N,2),1);V_myo*ones(num_rows,1)];
lambdaW = exp(pinv(M)*log(k_kinetic));
lambda = lambdaW./W;
kappa = lambda(1:size(N,2));
K = lambda(size(N,2)+1:end);
save([output_dir 'FCU_adenylylCyclase_BG_parameters.mat'],'kappa','K','k_kinetic');
%% Checks
N_rref = rref(N);
R_mat = null(N,'r');
k_est = exp(M*log(lambdaW));
diff = (k_kinetic - k_est)./k_kinetic;
error = sum(abs(diff));
K_eq = kf./kr;
if ~combined_kinetic_parameters
K_eq = K_eq';
end
zero_est = R_mat'*(K_eq);
zero_est_log = R_mat'*log(K_eq);
%% print outputs
for ik=1:length(kappa)
fprintf('var kappa_%s: fmol_per_sec {init: %g, pub: out};\n',rxnIDs{ik},kappa(ik));
end
for ik = 1:length(Kunique)
fprintf('var K_%s: per_fmol {init: %g, pub: out};\n',Kunique{ik},K(ik));
end
% initialise struct for storing modules contributing to a given K
for ik=1:length(Kunique)
Kname_modules.(Kunique{ik}) = {};
end
for i_system = 1:num_subsystems
sys_name = array_names{i_system};
modKname = sys_struct{i_system}.Kname;
for ik=1:length(modKname)
Kname_modules.(modKname{ik}) = [Kname_modules.(modKname{ik}), sys_name];
end
end
%% write out CellML code
if true
cpath = main_dir(Idx_backslash(end-1):Idx_backslash(end));
cellmlfilepath = [cpath(2:end-1) 'TEMP.cellml.txt'];
cid = fopen(cellmlfilepath,'w');
fwrite(cid, [sprintf('def model FCU_composite as\n def import using "units_and_constants/units_BG.cellml" for\n') ...
,sprintf('unit mM using unit mM;\nunit fmol using unit fmol;\nunit per_fmol using unit per_fmol;\n') ...
,sprintf('unit J_per_mol using unit J_per_mol;\nunit fmol_per_sec using unit fmol_per_sec;\n')...
,sprintf('unit C_per_mol using unit C_per_mol;\n unit J_per_C using unit J_per_C;\n')...
,sprintf('unit microm3 using unit microm3;\n unit fF using unit fF;\n')...
,sprintf('unit fC using unit fC;\n unit fA using unit fA;\n')...
,sprintf('unit per_second using unit per_second;\n unit millivolt using unit millivolt;\n')...
,sprintf('unit per_sec using unit per_sec;\n unit J_per_K_per_mol using unit J_per_K_per_mol;\n')...
,sprintf('unit fmol_per_L using unit fmol_per_L;\n unit fmol_per_L_per_sec using unit fmol_per_L_per_sec;\n')...
,sprintf('unit per_sec_per_fmol_per_L using unit per_sec_per_fmol_per_L;\n unit uM using unit uM;\n')...
,sprintf('unit mM_per_sec using unit mM_per_sec;\n unit uM_per_sec using unit uM_per_sec;\n')...
,sprintf('unit pL using unit pL;\n unit m_to_u using unit m_to_u;\n enddef;\n')]);
fwrite(cid,[sprintf('def import using "units_and_constants/constants_BG.cellml" for\n')...
,sprintf('comp constants using comp constants;\nenddef;\n\n')]);
for im = 1:length(array_names)
module = array_names{im};
fwrite(cid,sprintf('def import using "%s/BG_%s.cellml" for\ncomp %s using comp %s;\nenddef;\n',module,module,module,module));
end
fwrite(cid,sprintf('\ndef comp BG_parameters as\n'));
for ik=1:length(kappa)
fwrite(cid,sprintf('var kappa_%s: fmol_per_sec {init: %g, pub: out};\n',rxnIDs{ik},kappa(ik)));
end
for ik = 1:length(Kunique)
fwrite(cid,sprintf('var K_%s: per_fmol {init: %g, pub: out};\n',Kunique{ik},K(ik)));
end
fwrite(cid,sprintf('enddef;\n'));
fwrite(cid,[sprintf(' def comp environment as\n')...
,sprintf('var time: second;\n')...
,sprintf('var vol_myo: pL {init: 34.4, pub: out};\n')...
,sprintf('var freq: dimensionless {init: 500};\n')...
,sprintf('// stimulus\n')...
,sprintf('q_L_B1_init = sel\n')...
,sprintf(' case sin(2{dimensionless}*freq*pi*time) > 0.5{dimensionless}:\n')...
,sprintf(' 1e-13{fmol};\n')...
,sprintf(' otherwise:\n')...
,sprintf(' 1e-15{fmol};\n')...
,sprintf('endsel;\n')...
,sprintf('q_L_M2_init = sel\n')...
,sprintf(' case cos(2{dimensionless}*freq*pi*time) > 0.5{dimensionless}:\n')...
,sprintf(' 1e-13{fmol};\n')...
,sprintf(' otherwise:\n')...
,sprintf(' 1e-15{fmol};\n')...
,sprintf('endsel;\n')]);
for j=1:length(K)
fwrite(cid,sprintf('var q_%s_init: fmol {init: 1e-888};\n',Kunique{j}));
end
fwrite(cid,sprintf('\n// Global value\n'));
for j=1:length(K)
fwrite(cid,sprintf('var q_%s: fmol {pub: out};\n',Kunique{j}));
end
for im = 1:length(array_names)
module = array_names{im};
modKname = sys_struct{im}.Kname;
fwrite(cid,sprintf('\n// %s imports\n',module));
for j=1:length(modKname)
fwrite(cid,sprintf('var q_%s_m%s: fmol {pub: in};\n',modKname{j}, module));
end
fwrite(cid,newline);
end
fwrite(cid,newline);
for j=1:length(Kunique)
fwrite(cid,sprintf('q_%s = q_%s_init',Kunique{j},Kunique{j}));
for imod=1:length(Kname_modules.(Kunique{j}))
fwrite(cid,sprintf(' + q_%s_m%s ',Kunique{j},Kname_modules.(Kunique{j}){imod}));
end
fwrite(cid,sprintf(';\n'));
end
fwrite(cid,sprintf('enddef;\n'));
if false % the below is for an individual module
disp(newline)
disp('// Input from global environment');
for j=1:length(K)
fprintf('var q_%s_global: fmol {pub: in};\n',Kunique{j});
end
disp('// Output to global environment');
for j=1:length(K)
fprintf('var q_%s: fmol {init: 1e-16, pub: out};\n',Kunique{j});
end
for j=1:length(K)
fprintf('mu_%s = R*T*ln(K_%s*q_%s_global);\n',Kunique{j},Kunique{j},Kunique{j});
end
end
fwrite(cid,newline);
for im = 1:length(array_names)
module = array_names{im};
modKname = sys_struct{im}.Kname;
fwrite(cid,sprintf('def map between environment and %s for\n',module));
fwrite(cid,sprintf('vars time and time;\n'));
for j=1:length(modKname)
fwrite(cid,sprintf('vars q_%s_m%s and q_%s;\n',modKname{j}, module,modKname{j}));
fwrite(cid,sprintf('vars q_%s and q_%s_global;\n',modKname{j}, modKname{j}));
end
fwrite(cid,sprintf('enddef;\n\n'));
end
for im = 1:length(array_names)
module = array_names{im};
modKname = sys_struct{im}.Kname;
modrxnID = sys_struct{im}.rxnID;
fwrite(cid,sprintf('def map between BG_parameters and %s for\n',module));
for ik=1:length(modrxnID)
fwrite(cid,sprintf('vars kappa_%s and kappa_%s;\n',modrxnID{ik},modrxnID{ik}));
end
for j=1:length(modKname)
fwrite(cid,sprintf('vars K_%s and K_%s;\n',modKname{j}, modKname{j}));
end
fwrite(cid,sprintf('enddef;\n'));
end
fwrite(cid,newline);
for im = 1:length(array_names)
module = array_names{im};
fwrite(cid,sprintf('def map between constants and %s for\n', module));
fwrite(cid,sprintf('\tvars R and R;\n\tvars T and T;\nenddef;\n'));
end
fwrite(cid,sprintf('\nenddef;\n'));
fclose(cid);
end
%% FUNCTION SCRIPTS
function matrix = load_matrix(stoich_path)
stoich_file_id = fopen(stoich_path,'r');
stoich_file_data = textscan(stoich_file_id,'%s','delimiter','\n');
fclose(stoich_file_id);
num_rows = length(stoich_file_data{1});
num_cols = sum(stoich_file_data{1}{1} == ',')+1;
matrix = zeros(num_rows,num_cols);
for i_row = 1:num_rows
line_str = stoich_file_data{1}{i_row};
line_split = regexp(line_str,',','split');
for i_col = 1:num_cols
matrix(i_row,i_col) = str2double(line_split{i_col});
end
end
end
function T = calcT(I_vec,num_rows)
num_cols = length(I_vec);
T = zeros(num_rows,num_cols);
for i = 1:num_cols
T(I_vec(i),i) = 1;
end
end
