def reward_value_constrained(v_log_counts_future, v_log_counts_old,\
KQ_f_new, KQ_r_new, E_Regulation_new, E_Regulation_old):
final_reward = 0.0
reward_s = reward_intermediate(v_log_counts_future, v_log_counts_old)
#originally, does nothing, but turns to penalty value when regulating a new reaction
psi = 1.0
#reward_s = e_val_old-e_val_future
num_regulated_new = np.sum(E_Regulation_new == 1)
num_regulated_old = np.sum(E_Regulation_old == 1)
if (num_regulated_new != num_regulated_old):
#then you regulated a new reaction:
psi = penalty_reward_scalar
if ((reward_s < 0.0)):
final_reward = penalty_exclusion_reward
if (reward_s >= 0.0):
final_reward = psi * reward_s
#if negative (-0.01) -> take fastest path
#if positive (0.01) -> take slowest path
if ((np.max(v_log_counts_future - target_v_log_counts) <= 0.0)):
#The final reward is meant to maximize the EPR value. However, there was some residual error in ds_metab
#that must be taken into account. We therefore add the last reward_s to the EPR value.
epr_future = max_entropy_functions.entropy_production_rate(
KQ_f_new, KQ_r_new, E_Regulation_new)
final_reward = (1.0) * epr_future + psi * reward_s
return final_reward
def reward_value(v_log_counts_future, v_log_counts_old,\
KQ_f_new, KQ_r_new, E_Regulation_new, E_Regulation_old):
final_reward=0.0
#here we use the mean for the scaling. The logic is as follows:
#https://www.xarg.org/2016/06/the-log-sum-exp-trick-in-machine-learning/
scale_old_max = np.max(v_log_counts_old - target_v_log_counts)
scale_old_min = np.min(v_log_counts_old - target_v_log_counts)
scale_old = (scale_old_max + scale_old_min)/2.0
e_val_old = np.exp(v_log_counts_old - target_v_log_counts - scale_old)
e_val_old = scale_old + np.log(np.sum(e_val_old))
scale_future_max = np.max(v_log_counts_future - target_v_log_counts)
scale_future_min = np.min(v_log_counts_future - target_v_log_counts)
scale_future = (scale_future_max + scale_future_min)/2.0
e_val_future = np.exp(v_log_counts_future - target_v_log_counts - scale_future)
e_val_future = scale_future + np.log(np.sum(e_val_future))
reward_s = (e_val_old - e_val_future)
final_reward=reward_s
if (( scale_future_max <=0.0)):
#The final reward is meant to maximize the EPR value. However, there was some residual error
#that must be taken into account. We therefore add the last reward_s to the EPR value.
epr_future = max_entropy_functions.entropy_production_rate(KQ_f_new, KQ_r_new, E_Regulation_new)
final_reward = 1.0 * epr_future + reward_s
return final_reward
def reward_value(v_log_counts_future, v_log_counts_old,\
KQ_f_new, KQ_r_new, E_Regulation_new, E_Regulation_old):
final_reward = 0.0
reward_s = reward_intermediate(v_log_counts_future, v_log_counts_old)
final_reward = reward_s
if ((np.max(v_log_counts_future - target_v_log_counts) <= 0.0)):
#The final reward is meant to maximize the EPR value. However, there was some residual error in ds_metab
#that must be taken into account. We therefore add the last reward_s to the EPR value.
epr_future = max_entropy_functions.entropy_production_rate(
KQ_f_new, KQ_r_new, E_Regulation_new)
final_reward = (1.0) * epr_future + reward_s
return final_reward
def sarsa_n(nn_model, loss_fn, optimizer, scheduler, state_sample, n_back_step,
epsilon_greedy):
total_time_cpu = 0
total_time_nn = 0
#reset for each episode. policy will add
random_steps_taken = 0
nn_steps_taken = 0
final_state = []
final_KQ_f = []
final_KQ_r = []
reached_terminal_state = False
average_loss = []
final_reward = 0
sum_reward_episode = 0
end_of_path = 5000 #this is the maximum length a path can take
KQ_f_matrix = np.zeros(shape=(num_rxns, end_of_path + 1))
KQ_r_matrix = np.zeros(shape=(num_rxns, end_of_path + 1))
states_matrix = np.zeros(shape=(num_rxns, end_of_path + 1))
delta_S_metab_matrix = np.zeros(shape=(nvar, end_of_path + 1))
v_log_counts_matrix = np.zeros(shape=(nvar, end_of_path + 1))
states_matrix[:, 0] = state_sample
res_lsq = least_squares(max_entropy_functions.derivatives,
v_log_counts_static,
method='lm',
xtol=1e-15,
args=(f_log_counts, mu0, S_mat, R_back_mat, P_mat,
delta_increment_for_small_concs,
Keq_constant, states_matrix[:, 0]))
v_log_counts_matrix[:, 0] = res_lsq.x.copy()
log_metabolites = np.append(v_log_counts_matrix[:, 0], f_log_counts)
rxn_flux_init = max_entropy_functions.oddsDiff(
v_log_counts_matrix[:, 0], f_log_counts, mu0, S_mat, R_back_mat, P_mat,
delta_increment_for_small_concs, Keq_constant, states_matrix[:, 0])
KQ_f_matrix[:, 0] = max_entropy_functions.odds(
log_metabolites, mu0, S_mat, R_back_mat, P_mat,
delta_increment_for_small_concs, Keq_constant)
Keq_inverse = np.power(Keq_constant, -1)
KQ_r_matrix[:, 0] = max_entropy_functions.odds(
log_metabolites, mu0, -S_mat, P_mat, R_back_mat,
delta_increment_for_small_concs, Keq_inverse, -1)
delta_S_metab_matrix[:, 0] = max_entropy_functions.calc_deltaS_metab(
v_log_counts_matrix[:, 0], target_v_log_counts)
reward_vec = np.zeros(end_of_path + 1)
reward_vec[0] = 0.0
rxn_flux_path = rxn_flux_init.copy()
for t in range(0, end_of_path):
if (t < end_of_path):
#This represents the choice from the current policy.
[React_Choice,reward_vec[t+1],\
KQ_f_matrix[:,t+1], KQ_r_matrix[:,t+1],\
v_log_counts_matrix[:,t+1],\
states_matrix[:,t+1],\
delta_S_metab_matrix[:,t+1],\
used_random_step,time_cpu,time_nn] = policy_function(nn_model, states_matrix[:,t], v_log_counts_matrix[:,t], epsilon_greedy)#regulate each reaction.
total_time_cpu += time_cpu
total_time_nn += time_nn
if (used_random_step):
random_steps_taken += 1
else:
nn_steps_taken += 1
if (React_Choice == -1):
print("bad reaction choice, using action = -1")
break
rxn_flux_path = max_entropy_functions.oddsDiff(
v_log_counts_matrix[:, t + 1], f_log_counts, mu0, S_mat,
R_back_mat, P_mat, delta_increment_for_small_concs,
Keq_constant, states_matrix[:, t + 1])
if (np.max(rxn_flux_path) < 1.0):
print("draining flux")
break
epr_path = max_entropy_functions.entropy_production_rate(
KQ_f_matrix[:, t + 1], KQ_r_matrix[:, t + 1],
states_matrix[:, t + 1])
sum_reward_episode += reward_vec[t + 1]
current_state = states_matrix[:, t + 1].copy()
#We stop the path if we have no more positive loss function values, or if we revisit a state.
if ((delta_S_metab_matrix[:, t + 1] <= 0.0).all()):
end_of_path = t + 1 #stops simulation at step t+1
reached_terminal_state = True
final_state = states_matrix[:, t + 1].copy()
final_KQ_f = KQ_f_matrix[:, t + 1].copy()
final_KQ_r = KQ_r_matrix[:, t + 1].copy()
final_reward = epr_path
print(
"**************************************Path Length ds<0******************************************"
)
print(end_of_path)
print("Final STATE")
print(states_matrix[:, t + 1])
print(rxn_flux_path)
print("original epr")
print(epr_path)
print("all rewards")
print(reward_vec[0:t + 1])
##BEGIN LEARNING
tau = t - n_back_step + 1
if (tau >= 0):
#breakpoint()
estimate_value = torch.zeros(1, device=device)
for i in range(tau + 1, min(tau + n_back_step, end_of_path) + 1):
estimate_value += (gamma**(i - tau - 1)) * reward_vec[i]
if ((tau + n_back_step) < end_of_path):
begin_nn = time.time()
value_tau_n = state_value(
nn_model,
torch.from_numpy(
states_matrix[:,
tau + n_back_step]).float().to(device))
end_nn = time.time()
total_time_nn += end_nn - begin_nn
estimate_value += (gamma**(n_back_step)) * value_tau_n
begin_nn = time.time()
value_tau = state_value(
nn_model,
torch.from_numpy(states_matrix[:, tau]).float().to(device))
end_nn = time.time()
total_time_nn += end_nn - begin_nn
if (value_tau.requires_grad == False):
breakpoint()
if (estimate_value.requires_grad == True):
estimate_value.detach_()
#WARNING
#loss ordering should be input with requires_grad == True,
#followed by target with requires_grad == False
#breakpoint()
begin_nn = time.time()
loss = loss_fn(value_tau, estimate_value) #MSE
optimizer.zero_grad()
loss.backward()
clipping_value = 1.0
torch.nn.utils.clip_grad_norm_(nn_model.parameters(),
clipping_value)
optimizer.step()
end_nn = time.time()
total_time_nn += end_nn - begin_nn
average_loss.append(loss.item())
if (tau >= (end_of_path - 1)):
break
#after episode is finished, take average loss
average_loss_episode = np.mean(average_loss)
print("index of max error on path")
print(average_loss.index(max(average_loss)))
return [sum_reward_episode, average_loss_episode,max(average_loss),final_reward, final_state, final_KQ_f,final_KQ_r,\
reached_terminal_state, random_steps_taken,nn_steps_taken]
#make calculations to regulate
rxn_flux = max_entropy_functions.oddsDiff(v_log_counts, f_log_counts, mu0,
S_mat, R_back_mat, P_mat,
delta_increment_for_small_concs,
Keq_constant, E_regulation)
KQ_f = max_entropy_functions.odds(log_metabolites, mu0, S_mat, R_back_mat,
P_mat, delta_increment_for_small_concs,
Keq_constant)
Keq_inverse = np.power(Keq_constant, -1)
KQ_r = max_entropy_functions.odds(log_metabolites, mu0, -S_mat, P_mat,
R_back_mat,
delta_increment_for_small_concs,
Keq_inverse, -1)
epr = max_entropy_functions.entropy_production_rate(
KQ_f, KQ_r, E_regulation)
delta_S_metab = max_entropy_functions.calc_deltaS_metab(
v_log_counts, target_v_log_counts)
delta_S = max_entropy_functions.calc_deltaS(v_log_counts,
target_v_log_counts,
f_log_counts, S_mat, KQ_f)
[RR,
Jac] = max_entropy_functions.calc_Jac2(v_log_counts, f_log_counts, S_mat,
delta_increment_for_small_concs,
KQ_f, KQ_r, E_regulation)
A = max_entropy_functions.calc_A(v_log_counts, f_log_counts, S_mat, Jac,
E_regulation)
def sarsa_n(nn_model, loss_fn, optimizer, scheduler, state_sample, n_back_step,
epsilon_greedy):
#reset for each episode. policy will add
random_steps_taken = 0
nn_steps_taken = 0
maximum_predicted_value = 0
layer_weight = torch.zeros(1, device=device)
final_state = []
final_KQ_f = []
final_KQ_r = []
reached_terminal_state = False
average_loss = []
final_reward = 0
sum_reward_episode = 0
end_of_path = 1000 #this is the maximum length a path can take
states_matrix = np.zeros(shape=(num_rxns, end_of_path + 1))
states_matrix[:, 0] = state_sample
res_lsq = least_squares(max_entropy_functions.derivatives,
v_log_counts_static,
method=Method1,
bounds=(-500, 500),
xtol=1e-15,
args=(f_log_counts, mu0, S_mat, R_back_mat, P_mat,
delta_increment_for_small_concs,
Keq_constant, states_matrix[:, 0]))
if (res_lsq.success == False):
res_lsq = least_squares(max_entropy_functions.derivatives,
v_log_counts_static,
method=Method2,
xtol=1e-15,
args=(f_log_counts, mu0, S_mat, R_back_mat,
P_mat, delta_increment_for_small_concs,
Keq_constant, states_matrix[:, 0]))
if (res_lsq.success == False):
res_lsq = least_squares(max_entropy_functions.derivatives,
v_log_counts_static,
method=Method3,
xtol=1e-15,
args=(f_log_counts, mu0, S_mat, R_back_mat,
P_mat,
delta_increment_for_small_concs,
Keq_constant, states_matrix[:, 0]))
v_log_counts_current = res_lsq.x.copy()
log_metabolites = np.append(v_log_counts_current, f_log_counts)
rxn_flux_init = max_entropy_functions.oddsDiff(
v_log_counts_current, f_log_counts, mu0, S_mat, R_back_mat, P_mat,
delta_increment_for_small_concs, Keq_constant, states_matrix[:, 0])
KQ_f_current = max_entropy_functions.odds(log_metabolites, mu0, S_mat,
R_back_mat, P_mat,
delta_increment_for_small_concs,
Keq_constant)
Keq_inverse = np.power(Keq_constant, -1)
KQ_r_current = max_entropy_functions.odds(log_metabolites, mu0, -S_mat,
P_mat, R_back_mat,
delta_increment_for_small_concs,
Keq_inverse, -1)
delta_S_metab_current = max_entropy_functions.calc_deltaS_metab(
v_log_counts_current, target_v_log_counts)
#[ccc,fcc] = max_entropy_functions.conc_flux_control_coeff(nvar, A_init, S_mat, rxn_flux_init, RR)
reward_vec = np.zeros(end_of_path + 1)
reward_vec[0] = 0.0
rxn_flux_path = rxn_flux_init.copy()
#A_path = A_init.copy()
for t in range(0, end_of_path):
if (t < end_of_path):
#This represents the choice from the current policy.
[React_Choice,reward_vec[t+1],\
KQ_f_current, KQ_r_current,\
v_log_counts_current,\
states_matrix[:,t+1],\
delta_S_metab_current,\
used_random_step] = policy_function(nn_model, states_matrix[:,t], v_log_counts_current, epsilon_greedy)#regulate each reaction.
if (used_random_step):
random_steps_taken += 1
else:
nn_steps_taken += 1
if (React_Choice == -1):
print("out of rewards, final state")
print(states_matrix[:, t + 1])
break
rxn_flux_path = max_entropy_functions.oddsDiff(
v_log_counts_current, f_log_counts, mu0, S_mat, R_back_mat,
P_mat, delta_increment_for_small_concs, Keq_constant,
states_matrix[:, t + 1])
epr_path = max_entropy_functions.entropy_production_rate(
KQ_f_current, KQ_r_current, states_matrix[:, t + 1])
sum_reward_episode += reward_vec[t + 1]
final_state = states_matrix[:, t + 1].copy()
#We stop the path if we have no more positive loss function values, or if we revisit a state.
if ((delta_S_metab_current <= 0.0).all()):
end_of_path = t + 1 #stops simulation at step t+1
reached_terminal_state = True
final_state = states_matrix[:, t + 1].copy()
final_KQ_f = KQ_f_current.copy()
final_KQ_r = KQ_r_current.copy()
final_reward = epr_path
#breakpoint()
print(
"**************************************Path Length ds<0******************************************"
)
print(end_of_path)
print("Final STATE")
print(states_matrix[:, t + 1])
print(rxn_flux_path)
print("original epr")
print(epr_path)
print("all rewards:")
#print(reward_vec[0:t+1])
tau = t - n_back_step + 1
if (tau >= 0):
#THIS IS THE FORWARD
estimate_value = torch.zeros(1, device=device)
for i in range(tau + 1, min(tau + n_back_step, end_of_path) + 1):
estimate_value += (gamma**(i - tau - 1)) * reward_vec[i]
if ((tau + n_back_step) < end_of_path):
value_tau_n = state_value(
nn_model,
torch.from_numpy(
states_matrix[:,
tau + n_back_step]).float().to(device))
estimate_value += (gamma**(n_back_step)) * value_tau_n
value_tau = state_value(
nn_model,
torch.from_numpy(states_matrix[:, tau]).float().to(device))
if (value_tau.requires_grad == False):
print('value tau broken')
if (estimate_value.requires_grad == True):
estimate_value.detach_()
#THIS IS THE END OF FORWARD
#WARNING
#loss ordering should be input with requires_grad == True,
#followed by target with requires_grad == False
optimizer.zero_grad()
loss = (loss_fn(value_tau, estimate_value)) #currently MSE
loss.backward()
clipping_value = 1.0
#torch.nn.utils.clip_grad_value_(nn_model.parameters(), clipping_value)
torch.nn.utils.clip_grad_norm_(nn_model.parameters(),
clipping_value)
optimizer.step()
average_loss.append(loss.item())
if (tau >= (end_of_path - 1)):
break
#after episode is finished, take average loss
average_loss_episode = np.mean(average_loss)
#print(average_loss)
print("index of max error on path")
print(average_loss.index(max(average_loss)))
#print("All rewards")
#print(reward_vec[0:t+1])
return [sum_reward_episode, average_loss_episode,max(average_loss),final_reward, final_state, final_KQ_f,final_KQ_r,\
reached_terminal_state, random_steps_taken,nn_steps_taken]
