def circular(param, sequence, N):
g_stack = param[3]
g_base_pair = gm.generator(sequence, param[0], param[1], param[2], N)
Q = np.zeros((N,N))
for m in range(N):
Q[m,m-1] = 1.0
Qb = np.zeros((N,N))
Qs = np.zeros((N,N))
exp_neg_gloop_over_RT = np.exp(-g_loop*invRT)
exp_neg_gstack_gloop_over_RT = np.exp(-(g_stack-g_loop)*invRT)
for l in range(1, N+1): #length of subsequence
for i in range(0, N-l+1): # start of subsequence
j = i + l - 1
if j - i > 3 and (i + N) - j > 3 and g_base_pair[i,j]: # checking that base pair can form and bases are at least 4 positions apart on both sides
Qb[i,j] = Q_hairpin(g_base_pair[i,j])
else: # hairpin not possible
Qb[i,j] = 0.0
for d in range(i+1,j-4):
for e in range(d+4,j):
interior_loop_type = ''
if j - i > 3 and (i + N) - j > 3 and (d + N) - e > 3: #checking that the bases in each base pair are at least 4 positions apart
if g_base_pair[i,j] and g_base_pair[d,e]: # interior loop possible
if i+1 == d and e+1 == j: #stacked
interior_loop_type = 's' #g_interior = g_base_pair[i,j] + g_stack
else: #loop
interior_loop_type = 'l' #g_interior = g_base_pair[i,j] + g_loop
Qb[i,j] += Qb[d,e] * Q_interior(g_base_pair[i,j], g_stack, interior_loop_type)
else: # interior loop not possible
pass
else:
pass
# Qs recursion
for d in range(i+4, j+1): # iterate over all rightmost pairs with base i (beginning of subsequence)
Qs[i,j] += Qb[i,d]
Q[i,j] = 1.0
if i == 0 and j == N-1: # closing chain
for d in range(0, N-4):
if d == 0:
Q[i,j] += Qs[0,j]*exp_neg_gloop_over_RT
else:
if Qb[0,d-1] and Qb[d,N-1]: # to account for stacked pair forming when chain is closed
Q[i,j] += (Q[0,d-1] + Qs[0,d-1]*(exp_neg_gstack_gloop_over_RT - 1))*Qs[d,N-1]*exp_neg_gloop_over_RT
else: # to account for interior loop forming when chain is closed
Q[i,j] += Q[i,d-1]*Qs[d,j]*exp_neg_gloop_over_RT
else:
for d in range(i,j-3):
if d == 0:
Q[i,j] += Qs[d,j]
else:
Q[i,j] += Q[i,d-1]*Qs[d,j]
return Q[0,N-1]
def circular(param, sequence, N):
g_stack = param[3]
g_base_pair = gm.generator(sequence, param[0], param[1], param[2])
# initializing general partition matrix
Q = [[[0] for i in range(N)] for i in range(N)] # stores a,b,c, etc in exp(a) + exp(b) + ...
# initializing bound partition matrix
Qb = [[[] for i in range(N)] for i in range(N)]
Qs = [[[] for i in range(N)] for i in range(N)]
g_loop_over_RT = g_loop * invRT
g_stack_over_RT = g_stack * invRT
# calculation of partition function
for l in range(1,N+1): # iterating over all subsequence lengths
for i in range(0,N-l+1): # iterating over all starting positions for subsequences
j = i + l - 1 # ending position for subsequence
# Qb recursion
if j - i > 3 and (i + N) - j > 3 and g_base_pair[i,j]: # checking that base pair can form and bases are at least 4 positions apart on both sides
Qb[i][j].append(-(g_base_pair[i,j] + g_loop) * invRT)
for d in xrange(i+1,j-4): # iterate over all possible rightmost pairs
for e in xrange(d+4,j): # i < d < e < j and d,e must be at least 4 positions apart
interior_loop_type = ''
if j - i > 3 and (i + N) - j > 3 and (d + N) - e > 3: #checking that the bases in each base pair are at least 4 positions apart
if g_base_pair[i,j] and g_base_pair[d,e]: # interior loop possible
if i+1 == d and e+1 == j: #stacked
interior_loop_type = 's' #g_interior = g_base_pair[i,j] + g_stack
else: #loop
interior_loop_type = 'l' #g_interior = g_base_pair[i,j] + g_loop
Qb[i][j] += [ qb - g_interior(g_base_pair[i,j], g_stack, interior_loop_type)*invRT for qb in Qb[d][e] ]
for d in range(i+4, j+1):
Qs[i][j] += Qb[d][j]
# Q recursion
if i == 0 and j == N-1: # closing chain
for d in xrange(0, N-4):
if d == 0:
Q[i][j] += [ qs - g_loop_over_RT for qs in Qs[d][j] ]
else:
if len(Qb[0][d-1]) and len(Qb[d][N-1]): # to account for stacked pair forming when chain is closed
Q[i][j] += [ qs_k + q_m - g_loop_over_RT for qs_k in Qs[d][N-1] for q_m in Q[0][d-1] ]
for qs_k in Qs[d][N-1]:
for qs_w in Qs[0][d-1]:
g_partial = qs_k + qs_w
if (g_partial - g_loop*invRT) in Q[i][j]:
Q[i][j].remove(g_partial - g_loop_over_RT) # removing single instance; acting as subtracting a term
Q[i][j].append(g_partial - g_stack_over_RT)
else: # to account for interior loop forming when chain is closed
Q[i][j] += [ q + qs for q in Q[i][d-1] for qs in Qs[d][j] ]
else:
for d in xrange(i,j-3): # iterating over all possible rightmost pairs
if d == 0: # to deal with issue of wrapping around in the last iteration
Q[i][j] += Qs[d][j]
else:
Q[i][j] += [ qs + q for q in Q[i][d-1] for qs in Qs[d][j] ]
return sm.logsumexp(Q[0][N-1])
def linear(param, sequence, N):
g_stack = param[3]
g_base_pair = gm.generator(sequence, param[0], param[1], param[2], N)
# initializing general partition matrix
Q = np.zeros((N,N))
for m in range(N):
Q[m,m-1] = 1.0
# initializing bound partition matrix
Qb = np.zeros((N,N))
Qs = np.zeros((N,N))
# calculation of partition function
for ll in range(1,N+1): # iterating over all subsequence lengths
for ii in range(0,N-ll+1): # iterating over all starting positions for subsequences
jj = ii + ll - 1 # ending position for subsequence
# Qb recursion
if jj-ii > 3 and g_base_pair[ii,jj]: # if possible hairpin: at least 4 positions apart and able to form a base pair
Qb[ii,jj] = Q_hairpin(g_base_pair[ii,jj])
else: # no hairpin possible
Qb[ii,jj] = 0.0
for dd in range(ii+1,jj-4): # iterate over all possible rightmost pairs
for ee in range(dd+4,jj): # i < d < e < j and d,e must be at least 4 positions apart
interior_loop_type = ''
if g_base_pair[ii,jj] and g_base_pair[dd,ee]: # possible for both base pairs to form
if ii+1 == dd and ee+1 == jj: # if stacked
interior_loop_type = 's'
else: # if loop
interior_loop_type = 'l'
Qb[ii,jj] += Qb[dd,ee] * Q_interior(g_base_pair[ii,jj], g_stack, interior_loop_type)
else: # no interior loop possible (one or both base pairs can't form)
pass
# Qs recursion
for dd in range(ii+4, jj+1): # iterate over all rightmost pairs with base i (beginning of subsequence)
Qs[ii,jj] += Qb[ii,dd]
# Q recursion
Q[ii,jj] = 1.0
for dd in range(ii,jj-3): # iterating over all possible rightmost pairs
if dd == 0: # to deal with issue of wrapping around in the last iteration
Q[ii,jj] += Qs[dd,jj]
else:
Q[ii,jj] += Q[ii,dd-1]*Qs[dd,jj]
return Q[0,N-1]
def linear(param, sequence, N):
g_stack = param[3]
g_base_pair = gm.generator(sequence, param[0], param[1], param[2], N)
# initializing general partition matrix
Q = [[[0] for _ in range(N)] for _ in range(N)] # stores a,b,c, etc in exp(a) + exp(b) + ...
# initializing bound partition matrix
Qb = [[[] for _ in range(N)] for _ in range(N)]
Qs = [[[] for _ in range(N)] for _ in range(N)]
# calculation of partition function
for l in range(1,N+1): # iterating over all subsequence lengths
for i in range(0,N-l+1): # iterating over all starting positions for subsequences
j = i + l - 1 # ending position for subsequence
# Qb recursion
if j-i > 3 and g_base_pair[i,j]: # if possible hairpin: at least 4 positions apart and able to form a base pair
Qb[i][j].append(-(g_base_pair[i,j] + g_loop)*invRT)
for d in range(i+1,j-4): # iterate over all possible rightmost pairs
for e in range(d+4,j): # i < d < e < j and d,e must be at least 4 positions apart
interior_loop_type = ''
if g_base_pair[i,j] and g_base_pair[d,e]: # possible for both base pairs to form
if i+1 == d and e+1 == j: # if stacked
interior_loop_type = 's'
else: # if loop
interior_loop_type = 'l'
Qb[i][j] += [ qb - (g_interior(g_base_pair[i,j], g_stack, interior_loop_type)*invRT) for qb in Qb[d][e] ]
for d in range(i+4, j+1):
Qs[i][j] += Qb[d][j]
# Q recursion
for d in range(i,j-3): # iterating over all possible rightmost pairs
if d == 0: # to deal with issue of wrapping around in the last iteration
Q[i][j] += Qs[d][j]
else:
Q[i][j] += [ qs + q for qs in Qs[d][j] for q in Q[i][d-1] ]
return sm.logsumexp(Q[0][N-1]) #np.sum(np.exp(Q[0][N-1]))
def linear_derivatives(param, sequence, N, g): # g: energy parameter differentiating w.r.t.
g_stack = param[3]
g_base_pair = gm.generator(sequence, param[0], param[1], param[2], N)
# initializing general partition matrix
Q = np.zeros((N,N))
for m in range(N):
Q[m,m-1] = 1.0
dQ = np.zeros((N,N)) # stores derivatives
# initializing bound partition matrix
Qb = np.zeros((N,N))
dQb = np.zeros((N,N)) # stores bound derivatives
Qs = np.zeros((N,N))
dQs = np.zeros((N,N))
# LINEAR SEQUENCE calculation of partition function and its derivative
for ll in range(1,N+1): # iterating over all subsequence lengths
for ii in range(0,N-ll+1): # iterating over all starting positions for subsequences
jj = ii + ll - 1 # ending position for subsequence
# Qb recursion
if jj-ii > 3 and g_base_pair[ii,jj]: # if possible hairpin: at least 4 positions apart and able to form a base pair
q_hairpin_ij = Q_hairpin(g_base_pair[ii,jj])
Qb[ii,jj] = q_hairpin_ij
if g == g_base_pair[ii,jj]: # differentiating wrt current base pair parameter
dQb[ii,jj] = -q_hairpin_ij * invRT #(Q_hairpin(g_base_pair[i,j] + h, g_loop) - q_hairpin_ij)/h
else: # no hairpin possible
Qb[ii,jj] = 0.0
dQb[ii,jj] = 0.0
for dd in range(ii+1,jj-4): # iterate over all possible rightmost pairs
for ee in range(dd+4,jj): # i < d < e < j and d,e must be at least 4 positions apart
interior_loop_type = '' #g_interior = 0.0
if g_base_pair[ii,jj] and g_base_pair[dd,ee]: # possible for both base pairs to form
if ii+1 == dd and ee+1 == jj: # if stacked
interior_loop_type = 's' #g_interior = g_base_pair[i,j] + g_stack # avoids double counting free energy from base pair formation
else: # if loop
interior_loop_type = 'l' #g_interior = g_base_pair[i,j] + g_loop
q_int_ij = Q_interior(g_base_pair[ii,jj], g_stack, interior_loop_type)
Qb[ii,jj] += Qb[dd,ee] * q_int_ij
dQ_int = 0.0 # derivative of Q_interior
if g == g_base_pair[ii,jj]:
dQ_int = -q_int_ij * invRT #(Q_interior(g_base_pair[i,j] + h, g_loop, g_stack, interior_loop_type) - q_int_ij)/h
elif g == g_stack and interior_loop_type == 's':
dQ_int = -q_int_ij * invRT #(Q_interior(g_base_pair[i,j], g_loop, g_stack + h, interior_loop_type) - q_int_ij)/h
dQb[ii,jj] += dQ_int * Qb[dd,ee] + q_int_ij * dQb[dd,ee]
else: # no interior loop possible (one or both base pairs can't form)
pass
# Qs recursion
for dd in range(ii+4, jj+1): # iterate over all rightmost pairs with base i (beginning of subsequence)
Qs[ii,jj] += Qb[ii,dd]
dQs[ii,jj] += dQb[ii,dd]
# Q recursion
Q[ii,jj] = 1.0
for dd in range(ii,jj-3): # iterating over all possible rightmost pairs
if dd == 0: # to deal with issue of wrapping around in the last iteration
Q[ii,jj] += Qs[dd,jj]
dQ[ii,jj] += dQs[dd,jj]
else:
Q[ii,jj] += Q[ii,dd-1]*Qs[dd,jj]
dQ[ii,jj] += dQ[ii,dd-1]*Qs[dd,jj] + Q[ii,dd-1]*dQs[dd,jj]
return dQ[0,N-1]
def circular_derivatives_over_val(param, sequence, N, g):
g_stack = param[3]
g_base_pair = gm.generator(sequence, param[0], param[1], param[2], N)
Q = np.zeros((N,N))
for m in range(N):
Q[m,m-1] = 1.0
dQ = np.zeros((N,N))
Qb = np.zeros((N,N))
dQb = np.zeros((N,N))
Qs = np.zeros((N,N))
dQs = np.zeros((N,N))
exp_neg_gstack_gloop_over_RT = np.exp(-(g_stack-g_loop)*invRT)
for l in range(1, N+1): #length of subsequence
for i in range(0, N-l+1): # start of subsequence
j = i + l - 1
if j - i > 3 and (i + N) - j > 3 and g_base_pair[i,j]: # checking that base pair can form and bases are at least 4 positions apart on both sides
q_hairpin_ij = Q_hairpin(g_base_pair[i,j])
Qb[i,j] = q_hairpin_ij
if g == g_base_pair[i,j]:
dQb[i,j] = -q_hairpin_ij * invRT #(Q_hairpin(g_base_pair[i,j] + h, g_loop) - q_hairpin_ij)/h
else: # hairpin not possible
Qb[i,j] = 0.0
for d in range(i+1,j-4):
for e in range(d+4,j):
interior_loop_type = ''
if j - i > 3 and (i + N) - j > 3 and (d + N) - e > 3: #checking that the bases in each base pair are at least 4 positions apart
if g_base_pair[i,j] and g_base_pair[d,e]: # interior loop possible
if i+1 == d and e+1 == j: #stacked
interior_loop_type = 's' #g_interior = g_base_pair[i,j] + g_stack
else: #loop
interior_loop_type = 'l' #g_interior = g_base_pair[i,j] + g_loop
q_int_ij = Q_interior(g_base_pair[i,j], g_stack, interior_loop_type)
Qb[i,j] += Qb[d,e] * q_int_ij
dQ_int = 0.0
if g == g_base_pair[i,j]:
dQ_int = -q_int_ij * invRT #(Q_interior(g_base_pair[i,j] + h, g_loop, g_stack, interior_loop_type) - q_int_ij)/h
elif g == g_stack and interior_loop_type == 's':
dQ_int = -q_int_ij * invRT #(Q_interior(g_base_pair[i,j], g_loop, g_stack + h, interior_loop_type) - q_int_ij)/h
dQb[i,j] += dQ_int * Qb[d,e] + q_int_ij * dQb[d,e]
else: # interior loop not possible
pass
else:
pass
for d in range(i+4, j+1): # iterate over all rightmost pairs with base i (beginning of subsequence)
Qs[i,j] += Qb[i,d]
dQs[i,j] += dQb[i,d]
Q[i,j] = 1.0
if i == 0 and j == N-1: # closing chain
for d in range(0, N-4):
exp_neg_gloop_over_RT = np.exp(-g_loop*invRT)
if d == 0:
Q[i,j] += Qs[0,j]* exp_neg_gloop_over_RT
dQ[i,j] += dQs[0,j] * exp_neg_gloop_over_RT
else:
if Qb[0,d-1] and Qb[d,N-1]: # to account for stacked pair forming when chain is closed
Q[i,j] += (Q[0,d-1] + Qs[0,d-1]*(exp_neg_gstack_gloop_over_RT - 1))*Qs[d,N-1]*exp_neg_gloop_over_RT
if g == g_stack:
dQ[i,j] += (dQ[0,d-1] + dQs[0,d-1]*(exp_neg_gstack_gloop_over_RT -1) + Qs[0,d-1]*(-exp_neg_gstack_gloop_over_RT)*Qs[d,N-1]*exp_neg_gloop_over_RT)
dQ[i,j] += (Q[0,d-1] + Qs[0,d-1]*(exp_neg_gstack_gloop_over_RT - 1))*dQs[d,N-1]*exp_neg_gloop_over_RT
else:
dQ[i,j] += (dQ[0,d-1] + dQs[0,d-1]*(exp_neg_gstack_gloop_over_RT -1))*Qs[d,N-1]*exp_neg_gloop_over_RT
dQ[i,j] += (Q[0,d-1] + Qs[0,d-1]*(exp_neg_gstack_gloop_over_RT - 1))*dQs[d,N-1]*exp_neg_gloop_over_RT
else: # to account for interior loop forming when chain is closed
Q[i,j] += Q[i,d-1]*Qs[d,j]*exp_neg_gloop_over_RT
dQ[i,j] += dQ[i,d-1]*Qs[d,j]*exp_neg_gloop_over_RT + Q[i,d-1]*dQs[d,j]*exp_neg_gloop_over_RT
else:
for d in range(i,j-3):
if d == 0: # to deal with issue of wrapping around in the last iteration
Q[i,j] += Qs[d,j]
dQ[i,j] += dQs[d,j]
else:
Q[i,j] += Q[i,d-1]*Qs[d,j]
dQ[i,j] += dQ[i,d-1]*Qs[d,j] + Q[i,d-1]*dQs[d,j]
return dQ[0,N-1]/Q[0,N-1]
def circular_gradient(param, sequence, N):
g_stack = param[3]
g_base_pair = gm.generator(sequence, param[0], param[1], param[2], N)
# initializing general partition matrix
Q = np.zeros((N,N))
for m in range(N):
Q[m,m-1] = 1.0
dQ = np.zeros((N,N,4)) # stores gradients
# initializing bound partition matrix
Qb = np.zeros((N,N))
dQb = np.zeros((N,N,4)) # stores bound derivatives
Qs = np.zeros((N,N))
dQs = np.zeros((N,N,4))
# CIRCULAR SEQUENCE calculation of partition function and its derivative
for l in range(1,N+1): # iterating over all subsequence lengths
for i in range(0,N-l+1): # iterating over all starting positions for subsequences
j = i + l - 1 # ending position for subsequence
# Qb recursion
energy_index, = np.where(param == g_base_pair[i,j])
if j - i > 3 and (i + N) - j > 3 and g_base_pair[i,j]: # checking that base pair can form and bases are at least 4 positions apart on both sides
q_hairpin_ij = Q_hairpin(g_base_pair[i,j])
Qb[i,j] = q_hairpin_ij
dQb[i,j, energy_index] = -q_hairpin_ij * invRT #(Q_hairpin(g_base_pair[i,j] + h, g_loop) - q_hairpin_ij)/h
else: # no hairpin possible
pass
for d in range(i+1,j-4): # iterate over all possible rightmost pairs
for e in range(d+4,j): # i < d < e < j and d,e must be at least 4 positions apart
interior_loop_type = '' #g_interior = 0.0
if j - i > 3 and (i + N) - j > 3 and (d + N) - e > 3: #checking that the bases in each base pair are at least 4 positions apart
if g_base_pair[i,j] and g_base_pair[d,e]: # possible for both base pairs to form
if i+1 == d and e+1 == j: # if stacked
interior_loop_type = 's' #g_interior = g_base_pair[i,j] + g_stack # avoids double counting free energy from base pair formation
else: # if loop
interior_loop_type = 'l' #g_interior = g_base_pair[i,j] + g_loop
q_int_ij = Q_interior(g_base_pair[i,j], g_stack, interior_loop_type)
Qb[i,j] += Qb[d,e] * q_int_ij
dQ_int = np.zeros(4) # derivative of Q_interior
dQ_int[energy_index] = -q_int_ij * invRT #(Q_interior(g_base_pair[i,j] + h, g_loop, g_stack, interior_loop_type) - q_int_ij)/h
if interior_loop_type == 's':
dQ_int[3] = -q_int_ij * invRT #(Q_interior(g_base_pair[i,j], g_loop, g_stack + h, interior_loop_type) - q_int_ij)/h
dQb[i,j] += dQ_int * Qb[d,e] + q_int_ij * dQb[d,e]
else: # no interior loop possible (one or both base pairs can't form)
pass
else:
pass
# Qs recursion
for d in range(i+4, j+1): # iterate over all rightmost pairs with base i (beginning of subsequence)
Qs[i,j] += Qb[i,d]
dQs[i,j] += dQb[i,d]
# Q recursion
Q[i,j] = 1.0
if i == 0 and j == N-1: # closing chain
for d in range(0, N-4):
exp_neg_gloop_over_RT = np.exp(-g_loop*invRT)
if d == 0:
Q[i,j] += Qs[0,j]* exp_neg_gloop_over_RT
dQ[i,j] += dQs[0,j] * exp_neg_gloop_over_RT
else:
if Qb[0,d-1] and Qb[d,N-1]: # to account for stacked pair forming when chain is closed
Q[i,j] += (Q[0,d-1] + Qs[0,d-1]*(exp_neg_gstack_gloop_over_RT - 1))*Qs[d,N-1]*exp_neg_gloop_over_RT
dQ[i,j] += (Q[0,d-1] + Qs[0,d-1]*(exp_neg_gstack_gloop_over_RT - 1))*dQs[d,N-1]*exp_neg_gloop_over_RT
dQ[i,j] += (dQ[0,d-1] + dQs[0,d-1]*(exp_neg_gstack_gloop_over_RT -1))*Qs[d,N-1]*exp_neg_gloop_over_RT
dQ[i,j,3] += Qs[0,d-1]*(-exp_neg_gstack_gloop_over_RT)*Qs[d,N-1]*exp_neg_gloop_over_RT
else: # to account for interior loop forming when chain is closed
Q[i,j] += Q[i,d-1]*Qs[d,j]*exp_neg_gloop_over_RT
dQ[i,j] += dQ[i,d-1]*Qs[d,j]*exp_neg_gloop_over_RT + Q[i,d-1]*dQs[d,j]*exp_neg_gloop_over_RT
else:
for d in range(i,j-3):
if d == 0: # to deal with issue of wrapping around in the last iteration
Q[i,j] += Qs[d,j]
dQ[i,j] += dQs[d,j]
else:
Q[i,j] += Q[i,d-1]*Qs[d,j]
dQ[i,j] += dQ[i,d-1]*Qs[d,j] + Q[i,d-1]*dQs[d,j]
return dQ[0,N-1]
