def make_ecoli_df():
Ls = []
Ls_adj = []
ns = []
sigmas = []
labels = []
motif_ics = []
motif_ics_per_base = []
for tf in Escherichia_coli.tfs:
sites = getattr(Escherichia_coli, tf)
L = len(sites[0])
n = len(sites)
ns.append(n)
L_adj = len(sites[0]) + log2(n)
sigma = mean((map(sd, make_pssm(sites))))
Ls.append(L)
Ls_adj.append(L_adj)
motif_ics.append(motif_ic(sites))
motif_ics_per_base.append(motif_ic(sites) / float(L))
sigmas.append(sigma)
df = pd.DataFrame(
{
"L": Ls,
"n": ns,
"sigma": sigmas,
"motif_ic": motif_ics,
"info_density": motif_ics_per_base
},
index=Escherichia_coli.tfs)
return df
def match_ic_mi(N,
L,
des_ic,
des_mi,
iterations=50000,
take_stock=None,
eta=0.01,
alpha=1,
beta=0):
if take_stock is None:
take_stock = int((N * L) * log(N * L))
x = random_motif(L, N)
xs = [None] * iterations
ics = [0.0] * iterations
mis = [0.0] * iterations
alphas = [0.0] * iterations
betas = [0.0] * iterations
ic = motif_ic(x)
mi = total_motif_mi(x)
accepts = 0
for i in xrange(iterations):
# if i == iterations/2:
# eta *= 0.1
xp = mutate_motif(x)
icp = motif_ic(xp)
mip = total_motif_mi(xp)
log_y = (alpha * ic + beta * mi)
log_yp = (alpha * icp + beta * mip)
if log(random.random()) < log_yp - log_y:
accepts += 1
x = xp
ic = icp
mi = mip
ics[i] = (ic)
mis[i] = (mi)
xs[i] = (x)
#print sum(site.count("A") for site in x)
alphas[i] = (alpha)
betas[i] = (beta)
if i > 0 and i % take_stock == 0:
if i < iterations / 10:
mean_ic = mean(ics[i - take_stock:i])
mean_mi = mean(mis[i - take_stock:i])
alpha += eta * (des_ic - mean_ic) * exp(
-i / (10 * float(iterations)))
beta += eta * (des_mi - mean_mi) * exp(
-i / (10 * float(iterations)))
else:
mean_ic = mean(ics[i - take_stock:i])
mean_mi = mean(mis[i - take_stock:i])
alpha = poly1d(polyfit(ics[:i], alphas[:i], 1))(des_ic)
beta = poly1d(polyfit(mis[:i], betas[:i], 1))(des_mi)
fmt_string = (
"mean ic: % 1.2f, mean mi: % 1.2f, alpha: % 1.2f, beta: % 1.2f"
% (mean_ic, mean_mi, alpha, beta))
print i, "AR:", accepts / (i + 1.0), fmt_string
return xs, ics, mis, alphas, betas
def spoof_pmotifs(motif, num_motifs=10, trials=1):
n = len(motif)
L = len(motif[0])
des_ic = motif_ic(motif)
f = lambda p: -mean(
motif_ic(pmotif(n, L, p)) - des_ic for i in range(trials))
lb = 0
ub = 0.75
xs = np.linspace(lb, ub, 100)
ys = map(f, xs)
fhat = kde_regress(xs, ys)
p = bisect_interval(fhat, lb, ub, verbose=False, tolerance=10**-3)
return [pmotif(n, L, p) or _ in xrange(num_motifs)]
def flux_prob(motif, a, b, trials=10000):
"""determine probability of mutation pushing motif out of interval [a,b]"""
ic = motif_ic(motif)
lesser = 0
same = 0
greater = 0
for i in trange(trials):
icp = motif_ic(mutate_motif(motif))
if icp < a:
lesser += 1
elif a <= icp < b:
same += 1
else:
greater += 1
return lesser, same, greater
def spoof_motif_cftp(motif, num_motifs=10, trials=1, sigma=None,Ne_tol=10**-2,verbose=False):
n = len(motif)
L = len(motif[0])
copies = 10*n
if sigma is None: sigma = sigma_from_matrix(pssm_from_motif(motif,pc=1))
print "sigma:", sigma
bio_ic = motif_ic(motif)
matrix = sample_matrix(L, sigma)
mu = approx_mu(matrix, copies=10*n, G=5*10**6)
print "mu:", mu
def f(Ne):
motifs = [sample_motif_cftp(matrix, mu, Ne, n, verbose=verbose)
for i in trange(trials)]
return mean(map(motif_ic,motifs)) - bio_ic
# lb = 1
# ub = 10
# while f(ub) < 0:
# ub *= 2
# print ub
x0s = [2,10]#(lb + ub)/2.0
# print "choosing starting seed for Ne"
# fs = map(lambda x:abs(f(x)),x0s)
# print "starting values:",x0s,fs
# x0 = x0s[argmin(fs)]
# print "chose:",x0
# Ne = bisect_interval_noisy_ref(f,x0,lb=1,verbose=True)
Ne = log_regress_spec2(f,x0s,tol=Ne_tol)
print "Ne:",Ne
return [sample_motif_cftp(matrix, mu, Ne, n) for _ in trange(num_motifs)]
def interpret_main_experiment(results_dict,named_fs=None):
if named_fs is None:
named_fs = [(fitness,"fitness"),(lambda org:motif_ic(extract_sites(org)),"Motif IC"),
(lambda org:total_motif_mi(extract_sites(org)),"Motif MI")]
rec_muts,site_muts = map(lambda x:sorted(set(x)),transpose(results_dict.keys()))
fs,names = transpose(named_fs)
subplot_dimension = ceil(sqrt(len(fs)))
for idx,f in enumerate(fs):
mat = np.zeros((len(rec_muts),len(site_muts)))
for i,rec_mut in enumerate(sorted(rec_muts)):
for j,site_mut in enumerate(sorted(site_muts)):
pop,hist = results_dict[(rec_mut,site_mut)]
mat[i,j] = mean([f(x) for x,fit in pop])
print i,j,mat[i,j]
plt.subplot(subplot_dimension,subplot_dimension,idx)
plt.imshow(mat,interpolation='none')
plt.xticks(range(len(site_muts)),map(str,site_muts))
plt.yticks(range(len(rec_muts)),map(str,rec_muts))
#plt.yticks(rec_muts)
plt.xlabel("site mutation rate")
plt.ylabel("rec mutation rate")
plt.colorbar()
title = names[idx]
plt.title(title)
plt.show()
def Ne_scan(sigma, L, copies, trials=1, n=100, max_Ne=10, Ne_steps=100):
Ne_range = np.linspace(1, max_Ne, Ne_steps)
sigma = 1
plt.subplot(1, 4, 1)
obs_ics = map(
lambda Ne: mean(
motif_ic(sample_motif(sigma=sigma, Ne=Ne, L=L, n=n, copies=copies))
for _ in range(trials)), Ne_range)
pred_ics = map(lambda Ne: expected_ic(sigma, Ne, L, copies), Ne_range)
occs = map(lambda Ne: expected_occupancy(sigma, Ne, L, copies), Ne_range)
mismatches = map(lambda Ne: mismatch_probability(sigma, Ne, L, copies),
Ne_range)
plt.plot(Ne_range, obs_ics)
plt.plot(Ne_range, pred_ics)
plt.plot(Ne_range, occs)
plt.plot(Ne_range, mismatches)
plt.subplot(1, 4, 2)
plt.plot(mismatches, pred_ics)
plt.xlabel("Mismatches")
plt.ylabel("IC")
plt.subplot(1, 4, 3)
plt.plot(occs, pred_ics)
plt.xlabel("Occupancy")
plt.ylabel("IC")
plt.subplot(1, 4, 4)
plt.plot(mismatches, occs)
plt.xlabel("Mismatches")
plt.ylabel("Occs")
def sample_motif_cftp_param_study():
"""Examine dependence of IC on sigma, Ne"""
grid_points = 10
sigmas = np.linspace(0.5,10,grid_points)
Nes = np.linspace(1,10,grid_points)
trials = 3
n = 20
L = 10
def f(sigma, Ne):
matrix = sample_matrix(L, sigma)
mu = approx_mu(matrix, 10*n)
return motif_ic(sample_motif_cftp(matrix, mu, Ne, n))
ics = [[(mean(f(sigma, Ne) for _ in range(trials)))
for sigma in sigmas] for Ne in tqdm(Nes,desc="ic grid")]
plt.contourf(sigmas, Nes,ics)
plt.colorbar()
#bio_motifs = [getattr(Escherichia_coli,tf) for tf in Escherichia_coli.tfs]
bio_sigmas = [sigma_from_matrix(pssm_from_motif(motif,pc=1))
for motif in bio_motifs]
bio_ics = [motif_ic(motif) for motif in bio_motifs]
#griddata((sigmas,Nes),ics)
interp = interp2d(sigmas,Nes,ics)
bio_Nes = [bisect_interval(lambda Ne:interp(show(bio_sigma),Ne)-bio_ic,0,20)
for bio_sigma, bio_ic in zip(bio_sigmas,bio_ics)]
plt.scatter(sigm)
def interpret_main_experiment(results_dict, named_fs=None):
if named_fs is None:
named_fs = [(fitness, "fitness"),
(lambda org: motif_ic(extract_sites(org)), "Motif IC"),
(lambda org: total_motif_mi(extract_sites(org)),
"Motif MI")]
rec_muts, site_muts = map(lambda x: sorted(set(x)),
transpose(results_dict.keys()))
fs, names = transpose(named_fs)
subplot_dimension = ceil(sqrt(len(fs)))
for idx, f in enumerate(fs):
mat = np.zeros((len(rec_muts), len(site_muts)))
for i, rec_mut in enumerate(sorted(rec_muts)):
for j, site_mut in enumerate(sorted(site_muts)):
pop, hist = results_dict[(rec_mut, site_mut)]
mat[i, j] = mean([f(x) for x, fit in pop])
print i, j, mat[i, j]
plt.subplot(subplot_dimension, subplot_dimension, idx)
plt.imshow(mat, interpolation='none')
plt.xticks(range(len(site_muts)), map(str, site_muts))
plt.yticks(range(len(rec_muts)), map(str, rec_muts))
#plt.yticks(rec_muts)
plt.xlabel("site mutation rate")
plt.ylabel("rec mutation rate")
plt.colorbar()
title = names[idx]
plt.title(title)
plt.show()
def moran_process(N=1000,
turns=10000,
init=sample_species,
mutate=mutate,
fitness=fitness,
pop=None):
if pop is None:
pop = [(lambda spec: (spec, fitness(spec)))(sample_species())
for _ in trange(N)]
hist = []
for turn in xrange(turns):
fits = [f for (s, f) in pop]
#print fits
birth_idx = inverse_cdf_sample(range(N), fits, normalized=False)
death_idx = random.randrange(N)
#print birth_idx,death_idx
mother, f = pop[birth_idx]
daughter = mutate(mother)
#print "mutated"
pop[death_idx] = (daughter, fitness(daughter))
mean_fits = mean(fits)
hist.append((f, mean_fits))
if turn % 10 == 0:
mean_dna_ic = mean(
[motif_ic(sites, correct=False) for ((sites, eps), _) in pop])
mean_rec_h = mean(
[h_np(boltzmann(eps)) for ((dna, eps), _) in pop])
print turn, "sel_fit:", f, "mean_fit:", mean_fits, "mean_dna_ic:", mean_dna_ic, "mean_rec_h:", mean_rec_h
return pop
def main(prok_motifs, euk_motifs, filename='motif_summary_stats.eps'):
sns.set(style="darkgrid", color_codes=True)
#df = pd.DataFrame(columns="Type N L IC Gini".split(), index=range(len(prok_motifs) + len(euk_motifs)))
df = pd.DataFrame()
df['Domain'] = ["Eukaryotic" for _ in euk_motifs
] + ["Prokaryotic" for _ in prok_motifs]
motifs = euk_motifs + prok_motifs
df['N'] = [log(len(motif)) / log(10) for motif in motifs]
df['L (bp)'] = [len(motif[0]) for motif in motifs]
df['IC (bits)'] = [motif_ic(motif) for motif in motifs]
df['IGC'] = [motif_gini(motif) for motif in motifs]
pg = sns.pairplot(df,
hue='Domain',
markers='s o'.split(),
palette='cubehelix')
#hue_order=["Prokaryotic", "Eukaryotic"])
for i in range(4):
pg.axes[i][3].set_xlim(-0.01, 0.6)
for j in range(4):
pg.axes[3][j].set_ylim(-0.01, 0.6)
pg.axes[0][0].set_yticks(range(1, 5))
pg.axes[0][0].set_yticklabels(["$10^%i$" % i for i in range(1, 5)])
pg.axes[3][0].set_xticks(range(1, 5))
pg.axes[3][0].set_xticklabels(["$10^%i$" % i for i in range(1, 5)])
maybesave(filename)
def spoof_motifs(motif,
num_motifs=10,
trials=1,
sigma=None,
Ne_tol=10**-4,
double_sigma=True):
N = len(motif)
L = len(motif[0])
copies = 10 * N
if sigma is None:
sigma = sigma_from_matrix(pssm_from_motif(motif, pc=1))
epsilon = (1 + double_sigma) * sigma # 15 Jan 2016
print "sigma:", sigma
bio_ic = motif_ic(motif)
def f(Ne):
ps = ps_from_copies(sigma, Ne, L, copies)
motifs = [
sample_motif(epsilon, Ne, L, copies, n, ps=ps)
for i in range(trials)
]
return mean(map(motif_ic, motifs)) - bio_ic
Ne = log_regress_spec2(f, [1, 10], tol=10**-3)
return [sample_motif(sigma, Ne, L, copies, n) for _ in range(num_motifs)]
def Ne_scan(sigma,L,copies,trials=1,n=100,max_Ne=10,Ne_steps=100):
Ne_range = np.linspace(1,max_Ne,Ne_steps)
sigma = 1
plt.subplot(1,4,1)
obs_ics = map(lambda Ne:mean(motif_ic(sample_motif(sigma=sigma,Ne=Ne,L=L,n=n,copies=copies))
for _ in range(trials)), Ne_range)
pred_ics = map(lambda Ne:expected_ic(sigma,Ne,L,copies),Ne_range)
occs = map(lambda Ne:expected_occupancy(sigma,Ne,L,copies),Ne_range)
mismatches = map(lambda Ne:mismatch_probability(sigma,Ne,L,copies),Ne_range)
plt.plot(Ne_range,obs_ics)
plt.plot(Ne_range,pred_ics)
plt.plot(Ne_range,occs)
plt.plot(Ne_range,mismatches)
plt.subplot(1,4,2)
plt.plot(mismatches,pred_ics)
plt.xlabel("Mismatches")
plt.ylabel("IC")
plt.subplot(1,4,3)
plt.plot(occs,pred_ics)
plt.xlabel("Occupancy")
plt.ylabel("IC")
plt.subplot(1,4,4)
plt.plot(mismatches,occs)
plt.xlabel("Mismatches")
plt.ylabel("Occs")
def sigma_scan(Ne,L,copies,trials=1,n=100,sigma_steps=100,max_sigma=10):
sigma_range = np.linspace(1,max_sigma,sigma_steps)
sigma = 1
plt.subplot(1,4,1)
obs_ics = map(lambda sigma:mean(motif_ic(sample_motif(sigma=sigma,Ne=Ne,L=L,n=n,copies=copies))
for _ in range(trials)), sigma_range)
pred_ics = map(lambda sigma:expected_ic(sigma,Ne,L,copies),sigma_range)
occs = map(lambda sigma:expected_occupancy(sigma,Ne,L,copies),sigma_range)
mismatches = map(lambda sigma:mismatch_probability(sigma,Ne,L,copies),sigma_range)
mus = map(lambda sigma:mu_from(G,sigma,L,copies),sigma_range)
approx_mus = map(lambda sigma:approx_mu(G,sigma,L,copies),sigma_range)
mean_log_Zbs = map(lambda sigma:log(mean_Zb(sigma,L)),sigma_range)
plt.plot(sigma_range,obs_ics)
plt.plot(sigma_range,pred_ics)
plt.plot(sigma_range,occs)
plt.plot(sigma_range,mismatches)
plt.plot(sigma_range,mus)
plt.plot(sigma_range,approx_mus)
plt.plot(sigma_range,mean_log_Zbs)
plt.subplot(1,4,2)
plt.plot(mismatches,pred_ics)
plt.xlabel("Mismatches")
plt.ylabel("IC")
plt.subplot(1,4,3)
plt.plot(pred_ics,occs)
plt.xlabel("IC")
plt.ylabel("Occupancy")
plt.subplot(1,4,4)
plt.plot(mismatches,occs)
plt.xlabel("Mismatches")
plt.ylabel("Occs")
def biological_experiment(replicates=1000):
delta_ic = 0.1
results_dict = defaultdict(lambda:defaultdict(dict))
for tf_idx,tf in enumerate(Escherichia_coli.tfs):
print tf,"(%s/%s)" % (tf_idx,len(Escherichia_coli.tfs))
bio_motif = getattr(Escherichia_coli,tf)
n,L = motif_dimensions(bio_motif)
bio_ic = motif_ic(bio_motif)
bio_gini = motif_gini(bio_motif)
bio_mi = total_motif_mi(bio_motif)
results_dict[tf]["bio"]["motif_ic"] = bio_ic
results_dict[tf]["bio"]["motif_gini"] = bio_gini
results_dict[tf]["bio"]["total_motif_mi"] = bio_mi
beta = find_beta_for_mean_motif_ic(n,L,bio_ic)
maxent = maxent_motifs_with_ic(n,L,bio_ic,replicates)
#maxent_truncated = maxent_truncated_sample_motifs_with_ic(n,L,bio_ic,delta_ic,replicates,beta=beta)
uniform = uniform_motifs_with_ic(n,L,bio_ic,delta_ic,replicates)
#chain_spoofs = chain_sample_motifs_with_ic(n,L,bio_ic,delta_ic,replicates,beta=beta)
#for spoof_name in "maxent maxent_truncated envelope".split():
for spoof_name in "maxent uniform".split():
spoofs = eval(spoof_name)
for motif_statname in "motif_ic motif_gini total_motif_mi".split():
motif_stat = eval(motif_statname)
results_dict[tf][spoof_name][motif_statname] = map(motif_stat,spoofs)
#all_spoofs = [maxent_spoofs,maxent_truncated_spoofs,envelope_spoofs]#,chain_spoofs]
# print "IC:",bio_ic,map(lambda xs:val_in_coverage(bio_ic,xs),mmap(motif_ic,all_spoofs))
# print "Gini:",bio_gini,map(lambda xs:val_in_coverage(bio_gini,xs),mmap(motif_gini,all_spoofs))
# print "MI:",bio_mi,map(lambda xs:val_in_coverage(bio_mi,xs),mmap(total_motif_mi,all_spoofs))
return results_dict
def plot_results_dict_gini_qq(results_dict,filename=None):
bios = []
maxents = []
uniforms = []
for i,k in enumerate(results_dict):
g1,g2,tf = k.split("_")
genome = g1 + "_" + g2
bio_motif = extract_tfdf_sites(genome,tf)
bio_ic = motif_ic(bio_motif)
bio_gini = motif_gini(bio_motif)
d = results_dict[k]
bios.append(bio_gini)
maxents.append(mean(d['maxent']['motif_gini']))
uniforms.append(mean(d['uniform']['motif_gini']))
plt.scatter(bios,maxents,label='ME')
plt.scatter(bios,uniforms,label='TURS',color='g')
minval = min(bios+maxents+uniforms)
maxval = max(bios+maxents+uniforms)
plt.plot([minval,maxval],[minval,maxval],linestyle='--')
plt.xlabel("Observed Gini Coefficient")
plt.ylabel("Mean Sampled Gini Coefficient")
plt.legend(loc='upper left')
print "bio vs maxent:",pearsonr(bios,maxents)
print "bio vs uniform:",pearsonr(bios,uniforms)
maybesave(filename)
def gini_of_LGEs_experiment(iterations=50000,
Ne=200,
sigma=1,
lge_replicates=20):
"""Do motifs evolved under LGEs show more or less gini coefficient
than IC-matched maxent counterparts?"""
n = 16
L = 16
maxent_replicates = 1000
lge_motifs = []
lge_matrices = []
maxent_motifss = []
for i in range(lge_replicates):
matrix, chain = sella_hirsch_mh(Ne=Ne,
n=n,
L=L,
G=G,
sigma=sigma,
iterations=iterations,
init='ringer')
lge_motif = chain[-1]
desired_ic = motif_ic(lge_motif)
maxent_motifs = maxent_sample_motifs_with_ic(
n, L, desired_ic, replicates=maxent_replicates)
lge_matrices.append(matrix)
lge_motifs.append(lge_motif)
maxent_motifss.append(maxent_motifs)
return lge_matrices, lge_motifs, maxent_motifss
def moran_process(N=1000,turns=10000,mean_site_muts=1,mean_rec_muts=1,init=sample_species,mutate=mutate,
fitness=fitness,pop=None,print_modulus=100,hist_modulus=10):
#ringer = (np.array([1]+[0]*(K-1)),sample_eps())
if pop is None:
pop = [(lambda spec:(spec,fitness(spec)))(init())
for _ in trange(N)]
# ringer = make_ringer()
# pop[0] = (ringer,fitness(ringer))
#pop = [(ringer,fitness(ringer)) for _ in xrange(N)]
site_mu = min(1/float(n*L) * mean_site_muts,1)
rec_mu = min(1/float(K) * mean_rec_muts,1)
hist = []
for turn in xrange(turns):
fits = [f for (s,f) in pop]
#print fits
birth_idx = inverse_cdf_sample(range(N),fits,normalized=False)
if birth_idx is None:
return pop
death_idx = random.randrange(N)
#print birth_idx,death_idx
mother,f = pop[birth_idx]
daughter = mutate(mother,site_mu,rec_mu)
#print "mutated"
pop[death_idx] = (daughter,fitness(daughter))
mean_fits = mean(fits)
#hist.append((f,mean_fits))
if turn % hist_modulus == 0:
mean_dna_ic = mean([motif_ic(sites,correct=False) for ((sites,eps),_) in pop])
mean_rec = mean([recognizer_promiscuity(x) for (x,f) in pop])
mean_recced = mean([sites_recognized((dna,rec)) for ((dna,rec),_) in pop])
hist.append((turn,f,mean_fits,mean_dna_ic,mean_rec,mean_recced))
if turn % print_modulus == 0:
print turn,"sel_fit:",f,"mean_fit:",mean_fits,"mean_dna_ic:",mean_dna_ic,"mean_rec_prom:",mean_rec
return pop,hist
def L_vs_sigma_plot(filename=None, with_bio=False):
if with_bio:
tfdf = extract_motif_object_from_tfdf()
motifs = [getattr(tfdf, tf) for tf in tfdf.tfs]
Ls = [len(motif[0]) for motif in motifs]
cs = [len(motif) for motif in motifs]
ics = [motif_ic(motif) for motif in motifs]
ic_density = [ic / L for ic, L in zip(ics, Ls)]
sigmas = [mean(map(sd, make_pssm(motif))) for motif in motifs]
ginis = [motif_gini(motif, correct=False) for motif in motifs]
mi_density = [
total_motif_mi(motif) / choose(L, 2)
for motif, L in zip(motifs, Ls)
]
min_sigma = 0.1
max_sigma = 10
plt.xlim(0, max_sigma)
plt.ylim(0, 60)
plt.plot(*pl(crit_L, np.linspace(min_sigma, max_sigma, 1000)),
label="Binding Transition")
plt.plot([min_sigma, max_sigma],
[log(G, 2) / 2, log(G, 2) / 2],
linestyle='--',
label="Info Theory Threshold")
# plt.plot(*pl(lambda sigma:log(G)/sigma,np.linspace(min_sigma,max_sigma,1000)),
# linestyle='--',label="Zero Discrimination Asymptote")
if with_bio:
plt.scatter(sigmas, Ls, label="Biological Motifs")
plt.xlabel("sigma")
plt.ylabel("L")
plt.legend()
maybesave(filename)
def sample_motifs_evo_ic(motif, iterations=1000, verbose=False, theta=None):
N = len(motif)
L = len(motif[0])
des_ic = motif_ic(motif)
chain = evo_ic_sample_motif2(N, L, des_ic, iterations=iterations, verbose=False, theta=theta)
motifs = [sample_motif_cftp(sample_matrix(L, sigma), mu, Ne, N) for (sigma, mu, Ne) in tqdm(chain)]
return chain, motifs
def train_pairwise_model2(motif,
pc=1 / 16.0,
decay_timescale=10000,
take_stock=1000,
eta=0.01,
stop_crit=0.01):
L = len(motif[0])
N = len(motif)
fs = get_pairwise_freqs(motif, pc=pc)
ws = [{(b1, b2): 0
for (b1, b2) in dinucs} for _ in range(int(choose(L, 2)))]
iteration = 0
while True:
cur_motif = [
sample_model(ws, x0=site, iterations=10 * L)[-1] for site in motif
]
current_fs = get_pairwise_freqs(cur_motif)
sse = 0
for w, f, cur_f in zip(ws, fs, current_fs):
for b1, b2 in dinucs:
delta = f[b1, b2] - cur_f[b1, b2]
sse += delta**2
w[b1, b2] += eta * (
delta) #* exp(-iteration/float(decay_timescale))
#sses[iteration/take_stock] = sse
sse_per_col_pair = sse / choose(L, 2)
print iteration, sse_per_col_pair, ws[0]['A', 'A']
print "motif_ic:", motif_ic(cur_motif)
if iteration > 0 and sse_per_col_pair < stop_crit:
print "breaking:", sse, sse_per_col_pair
break
iteration += 1
return ws
def spoof_motif_ref(motif,
num_motifs=10,
trials=10,
sigma=None,
Ne_tol=10**-4):
n = len(motif)
L = len(motif[0])
copies = 10 * n
if sigma is None:
sigma = sigma_from_matrix(pssm_from_motif(motif, pc=1))
print "sigma:", sigma
bio_ic = motif_ic(motif)
def f(Ne):
ps = ps_from_copies(sigma, Ne, L, copies)
motifs = [
sample_motif(sigma, Ne, L, copies, n, ps=ps) for i in range(trials)
]
return mean(map(motif_ic, motifs)) - bio_ic
lb = 1
ub = 2
while f(ub) < 0:
ub *= 2
ub *= 2 # once more for good measure
x0 = (lb + ub) / 2.0
print "Ne guess:", x0
Nes = [
bisect_interval_noisy(f, x0=x0, tolerance=Ne_tol, lb=1)
for i in range(3)
]
Ne = mean(Nes)
print "Nes:", Nes, Ne
return [sample_motif(sigma, Ne, L, copies, n) for _ in range(num_motifs)]
def main_experiment(motif_obj):
"""compare gini biological motifs to:
(1) null ic-matched ensembles,and
(2) sigma and IC matched evosims.
Conduct evosims by matching sigma to pssm (fair?) and sweeping Ne in order to match IC.
"""
evosim_trials = 10
for tf in motif_obj.tfs:
bio_motif = getattr(motif_obj, tf)
n, L = len(bio_motif), len(bio_motif[0])
bio_gini = motif_gini(bio_motif)
bio_ic = motif_ic(bio_motif)
bio_mi = total_motif_mi(bio_motif)
###############
### null ensemble stuff here
###############
pssm = make_pssm(bio_motif)
sigma = mean(map(sd, pssm)) # revisit this, see Djordjevic's paper
# determine Ne
Ne_ic = {}
lo = 0
hi = 5
#Ne_ic[lo] =
chain = sella_hirsch_mh_gr(matrix,
Ne=5,
iterations=1000,
n=16,
x0s=None)
print "sigma:", sigma
for trial in trange(evosim_trials):
matrix = sample_matrix(L, sigma)
def moran_process(mean_rec_muts,
mean_site_muts,
N=1000,
turns=10000,
init=make_ringer2,
mutate=mutate,
fitness=fitness,
pop=None):
site_mu = mean_site_muts / float(n * L)
bd_mu = mean_rec_muts / float(L)
if pop is None:
pop = [(lambda spec: (spec, fitness(spec)))(init()) for _ in trange(N)]
hist = []
for turn in xrange(turns):
fits = [f for (s, f) in pop]
birth_idx = inverse_cdf_sample(range(N), fits, normalized=False)
death_idx = random.randrange(N)
#print birth_idx,death_idx
mother, f = pop[birth_idx]
daughter = mutate(mother, site_mu, bd_mu)
#print "mutated"
pop[death_idx] = (daughter, fitness(daughter))
mean_fits = mean(fits)
hist.append((f, mean_fits))
if turn % 1000 == 0:
mean_dna_ic = mean(
[motif_ic(sites, correct=False) for ((bd, sites), _) in pop])
print turn, "sel_fit:", f, "mean_fit:", mean_fits, "mean_dna_ic:", mean_dna_ic
return pop, hist
def spoof_motifs_maxent(motif, num_motifs, verbose=False):
n = len(motif)
L = len(motif[0])
des_ic = motif_ic(motif)
if verbose:
print "n: {} L: {} des_ic: {}".format(n, L, des_ic)
return maxent_motifs_with_ic(n, L, des_ic, num_motifs, verbose=verbose)
def best_ic_motif(L,n,trials):
best_ic = 0
for i in trange(trials):
motif = random_motif(L,n)
cur_ic = motif_ic(motif,correct=False)
if cur_ic > best_ic:
best_motif = motif
return best_motif
def analyze_bio_motifs(Nes,trials=20):
results = {}
for tf_idx,tf in enumerate(Escherichia_coli.tfs):
Ne = Nes[tf]
bio_motif = getattr(Escherichia_coli,tf)
n,L = len(bio_motif),len(bio_motif[0])
bio_matrix = matrix_from_motif(bio_motif)
sigma = sigma_from_matrix(bio_matrix)
matrix_chains = [sella_hirsch_mh(n=n,L=L,sigma=sigma,Ne=Ne,init='ringer') for i in range(trials)]
ics = [mean(map(motif_ic,chain[-1000:])) for (matrix,chain) in matrix_chains]
ginis = [mean(map(motif_gini,chain[-1000:])) for (matrix,chain) in matrix_chains]
mis = [mean(map(total_motif_mi,chain[-1000:])) for (matrix,chain) in matrix_chains]
print "results for:",tf,tf_idx
print motif_ic(bio_motif),mean(ics),sd(ics)
print motif_gini(bio_motif),mean(ginis),sd(ginis)
print total_motif_mi(bio_motif),mean(mis),sd(mis)
results[tf] = (mean(ics),sd(ics),mean(ginis),sd(ginis),mean(mis),sd(mis))
return results
def recognizer_non_linearity((sites,recognizer)):
L = log(len(idx_of_word),4)
motif = [w for w,i in idx_of_word.items() if recognizer[i]]
if len(motif) == 0:
return -1
else:
total_info = 2*L - log2(len(motif))
col_info = motif_ic(motif,correct=False)
return total_info - col_info
def spoof_motifs_uniform(motif, num_motifs, epsilon=0.1, verbose=False):
n, L = len(motif), len(motif[0])
desired_ic = motif_ic(motif)
if verbose: print "starting spoof motifs uniform with:", n, L, desired_ic
return uniform_motifs_accept_reject(n,
L,
desired_ic,
num_motifs,
epsilon,
verbose=verbose)
def interpret_main_experiment(results_dict):
taus = sorted(results_dict.keys())
print taus
data = [(tau,f,motif_ic(extract_sites(s)),total_motif_mi(extract_sites(s)))
for tau in taus for (s,f) in results_dict[tau][0]]
cols = transpose(data)
names = "tau,f,motif_ic,total_motif_mi".split(",")
for (i,name1),(j,name2) in choose2(list(enumerate(names))):
xs = cols[i]
ys = cols[j]
print name1,name2,pearsonr(xs,ys),spearmanr(xs,ys)
def fit_motif(motif):
n = len(motif)
L = len(motif[0])
bio_ic = motif_ic(motif)
def f((sigma,Ne,copies)):
return expected_ic(sigma,Ne,L,copies)-bio_ic
def fsq((sigma,Ne,copies)):
return f((sigma,Ne,copies))**2
x0 = (1,2,n)
fit_params = minimize(fsq,x0,bounds=((0,10),(1,None),(1,None)),method='TNC').x
return fit_params
def main_experiment(samples=30, iterations=10000, delta_ic=0.1):
results_dict = {}
for tf_idx, tf in enumerate(tfdf.tfs):
print "starting on:", tf
motif = getattr(tfdf, tf)
if motif_ic(motif) < 5:
print "excluding", tf, "for low IC"
continue
bio_ic = motif_ic(motif)
n = len(motif)
L = len(motif[0])
matrix = matrix_from_motif(motif)
sigma = sigma_from_matrix(matrix)
mu = approximate_mu(matrix, n, G)
Ne = estimate_Ne(matrix, mu, n, bio_ic)
spoofs = []
ar = 0
spoof_trials = 0.0
while len(spoofs) < samples:
spoof_trials += 1
matrix, chain = sella_hirsch_mh(Ne=Ne,
mu=mu,
n=1,
matrix=sample_matrix(L, sigma),
init='ringer',
iterations=iterations)
spoof_motif = concat(
[random.choice(chain[iterations / 2:]) for i in range(n)])
if abs(motif_ic(spoof_motif) - bio_ic) < delta_ic:
spoofs.append(spoof_motif)
ar += 1
print "spoof acceptance rate:", ar / spoof_trials, len(
spoofs), samples, spoof_trials
#spoofs = [chain[-1] for (spoof_matrix,chain,Ne) in [spoof_motif(motif,Ne) for i in range(samples)]]
results_dict[tf] = {
fname: map(eval(fname), spoofs)
for fname in "motif_ic motif_gini total_motif_mi".split()
}
print "finished:", tf, "(%s/%s)" % (tf_idx, len(tfdf.tfs))
print bio_ic, mean_ci(results_dict[tf]['motif_ic'])
return results_dict
def motif_degradation_experiment():
"""what is the effect of repeatedly inferring a motif from selected sites?"""
from motifs import Escherichia_coli
motif = Escherichia_coli.LexA
n = len(motif)
matrix = matrix_from_motif(motif)
assumed_copies = 10 * n
mu = approximate_mu(matrix, assumed_copies, G)
for i in range(10):
print i, "motif ic:", motif_ic(motif)
motif = select_sites_by_occupancy(matrix, mu, n)
matrix = matrix_from_motif(motif)
def interpret_main_experiment(results_dict):
taus = sorted(results_dict.keys())
print taus
data = [(tau, f, motif_ic(extract_sites(s)),
total_motif_mi(extract_sites(s))) for tau in taus
for (s, f) in results_dict[tau][0]]
cols = transpose(data)
names = "tau,f,motif_ic,total_motif_mi".split(",")
for (i, name1), (j, name2) in choose2(list(enumerate(names))):
xs = cols[i]
ys = cols[j]
print name1, name2, pearsonr(xs, ys), spearmanr(xs, ys)
def plot_mono_vs_di_likelihood(ll_dict = None):
if ll_dict is None:
ll_dict = likelihood_dict()
normed_dict = {tf:tuple(map(lambda x:x/float(len(getattr(Escherichia_coli,tf))*len(getattr(Escherichia_coli,tf)[0])),(mono,di))) for (tf,(mono,di)) in ll_dict.items()}
plt.scatter(*transpose(ll_dict.values()))
for (tf,(mono,di)) in ll_dict.items():
sites = getattr(Escherichia_coli,tf)
text = "%s\n#:%s\nw:%s\nIC:%1.2f" % (tf,len(sites),len(sites[0]),motif_ic(sites))
plt.annotate(text,(mono,di))
min_val = min(concat(ll_dict.values()))
max_val = max(concat(ll_dict.values()))
plt.xlabel("Mono LL")
plt.ylabel("Di LL")
plt.plot([min_val,max_val],[min_val,max_val],linestyle="--")
def motif_ls_sq_surface_experiment():
motif = Escherichia_coli.LexA
L = len(motif[0])
bio_ic = motif_ic(motif)
sigma,Ne,copies = fit_motif(motif)
fit_ic = expected_ic(sigma,Ne,L,copies)
f = lambda (sigma,Ne,copies):expected_ic(sigma,Ne,L,copies)
gr = compute_grad(f,(sigma,Ne,copies),epsilon=0.0001)
hess = compute_hessian(f,(sigma,Ne,copies))
lambs, vs = np.linalg.eig(hess)
def orth_comp(y,z):
a,b,c = gr
x = -(b*y+c*z)/a
return np.array([x,y,z])
def interpret_estremo_chain(chain, mu=-10, Ne=5):
nu = Ne - 1
def log_f((code, motif)):
eps = map(lambda x: -log(x), pw_prob_sites(motif, code))
return sum(nu * log(1 / (1 + exp(ep - mu))) for ep in eps)
spoofs = [spoof_maxent_motifs(motif, 10) for code, motif in tqdm(chain)]
plt.plot([motif_ic(motif) for (code, motif) in tqdm(chain)])
plt.plot([motif_mi(motif) for (code, motif) in tqdm(chain)])
plt.plot([mean(map(motif_ic, motifs)) for motifs in tqdm(spoofs)])
plt.plot([mean(map(motif_mi, motifs)) for motifs in tqdm(spoofs)])
plt.plot([indep_measure(code) for (code, motif) in tqdm(chain)])
plt.plot(map(log_f, chain))
def spoof_motif(motif, T):
n = len(motif)
L = len(motif[0])
bio_ic = motif_ic(motif)
sigma = 2 * mean(map(sd, make_pssm(motif))) # XXX REVSIT THIS ISSUE
ic_from_Ne = lambda Ne: predict_stat(n,
L,
sigma,
Ne,
G=5 * 10**6,
T=lambda rho: mean_ic_from_rho(
rho, n, L))
Ne = bisect_interval(lambda Ne: ic_from_Ne(Ne) - bio_ic, 0.01, 5)
return predict_stat(n, L, sigma, Ne, T)
def collapsed_moran_process(N,turns,init=sample_species,mutate=mutate,fitness=fitness,ancestor=None,modulus=100):
if ancestor is None:
ancestor = sample_species()
f = fitness(ancestor)
hist = []
for turn in xrange(turns):
prop = mutate(ancestor)
fp = fitness(prop)
if f == fp:
continue
num = (1-f/fp)
denom = (1-(f/fp)**N)
transition_prob = num/denom
# print f,fp
# print num,denom
# print transition_prob
if random.random() < transition_prob:
ancestor = prop
f = fp
if turn % modulus == 0:
print (turn,f,f,motif_ic(ancestor[0],correct=False),rec_h(ancestor[1]))
hist.append((turn,f,f,motif_ic(ancestor[0]),rec_h(ancestor[1])))
return ancestor,hist
def basic_statistics(tfdf=None,filename="basic_motif_statistics.png"):
if tfdf is None:
tfdf = extract_motif_object_from_tfdf()
motifs = [getattr(tfdf,tf) for tf in tfdf.tfs]
Ls = [len(motif[0]) for motif in motifs]
ns = [len(motif) for motif in motifs]
ics = [motif_ic(motif) for motif in motifs]
ic_density = [ic/L for ic,L in zip(ics,Ls)]
sigmas = [mean(map(sd,make_pssm(motif))) for motif in motifs]
ginis = [motif_gini(motif,correct=False) for motif in motifs]
mi_density = [total_motif_mi(motif)/choose(L,2) for motif,L in zip(motifs,Ls)]
plt.subplot(2,3,1)
#plt.tick_params(axis='x',pad=15)
plt.xticks(rotation=90)
plt.hist(Ls)
plt.xlabel("Length (bp)")
plt.subplot(2,3,2)
#plt.tick_params(axis='x',pad=30)
plt.xticks(rotation=90)
plt.hist(ns)
plt.xlabel("Number of sites")
plt.subplot(2,3,3)
plt.hist(ics)
plt.xticks(rotation=90)
plt.xlabel("IC (bits)")
plt.subplot(2,3,4)
#plt.tick_params(axis='x',pad=30)
plt.xticks(rotation=90)
plt.hist(ic_density)
plt.xlabel("IC Density (bits/bp)")
plt.subplot(2,3,5)
#plt.tick_params(axis='x',pad=15)
plt.xticks(rotation=90)
plt.hist(ginis)
plt.xlabel("Gini coeff")
plt.subplot(2,3,6)
#plt.tick_params(axis='x',pad=30)
plt.xticks(rotation=90)
plt.hist(mi_density)
plt.xlabel("MI Density (bits/comparison)")
plt.tight_layout()
if filename:
plt.savefig(filename,dpi=600)
plt.close()
def test_predict_ic(trials=100):
pred_ics = []
obs_ics = []
for trial in trange(trials):
sigma = random.random() * 5 + 0.1
L = random.randrange(5, 15)
matrix = sample_matrix(L, sigma)
mu = random.random() * (-20)
Ne = random.random() * 5 + 1
pred_ic = predict_ic(matrix, mu, Ne)
obs_ic = motif_ic(sample_motif_cftp(matrix, mu, Ne, n=100))
pred_ics.append(pred_ic)
obs_ics.append(obs_ic)
r, p = scatter(pred_ics, obs_ics)
print r, p
def sample_motifs_evo_ic(motif, iterations=1000, verbose=False, theta=None):
N = len(motif)
L = len(motif[0])
des_ic = motif_ic(motif)
chain = evo_ic_sample_motif2(N,
L,
des_ic,
iterations=iterations,
verbose=False,
theta=theta)
motifs = [
sample_motif_cftp(sample_matrix(L, sigma), mu, Ne, N)
for (sigma, mu, Ne) in tqdm(chain)
]
return chain, motifs
def test():
L = 10
matrix = [[-1,0,0,0] for i in range(L)]
ringer_site = "A"*L
n = 10
trials = 10
mus = range(-9,1,1)
Nes = range(2,11,1)
ics = [[mean(motif_ic(sample_motif(matrix, show(mu), Ne, ringer_site, n))
for i in range(trials)) for mu in tqdm(mus)]
for Ne in Nes]
plt.contour(mus,Nes,ics)
plt.colorbar(label="IC")
plt.xlabel("Mu")
plt.ylabel("Nes")
def find_beta(N, L, des_ic, iterations=100, verbose=False):
#des_ic_per_col = des_ic / float(L)
beta = 1
alpha = 1.0
beta_hist = []
ic_hist = []
for i in range(1,iterations+1):
#beta = beta + alpha/i * (des_ic_per_col - motif_ic(rmotif(N, 1, beta)))
obs_ic = motif_ic(rmotif(N, L, beta))
beta_hist.append(beta)
ic_hist.append(obs_ic)
beta = beta + alpha/i * (des_ic - obs_ic)
if verbose:
print i, beta, obs_ic
return beta, beta_hist, ic_hist
def plot_results_dict_gini_vs_ic(results_dict,filename=None):
for i,k in enumerate(results_dict):
g1,g2,tf = k.split("_")
genome = g1 + "_" + g2
bio_motif = extract_tfdf_sites(genome,tf)
bio_ic = motif_ic(bio_motif)
bio_gini = motif_gini(bio_motif)
d = results_dict[k]
plt.scatter(bio_ic,bio_gini,color='b',label="Bio"*(i==0))
plt.scatter(mean(d['maxent']['motif_ic']),mean(d['maxent']['motif_gini']),color='g',label='ME'*(i==0))
plt.scatter(mean(d['uniform']['motif_ic']),mean(d['uniform']['motif_gini']),color='r',label="TURS"*(i==0))
plt.xlabel("IC (bits)")
plt.ylabel("Gini Coefficient")
plt.legend()
maybesave(filename)
def test_predict_ic(trials=100):
pred_ics = []
obs_ics = []
for trial in trange(trials):
sigma = random.random() * 5 + 0.1
L = random.randrange(5, 15)
matrix = sample_matrix(L, sigma)
mu = random.random() * (-20)
Ne = random.random() * 5 + 1
pred_ic = predict_ic(matrix, mu, Ne)
obs_ic = motif_ic(sample_motif_cftp(matrix, mu, Ne, n=100))
pred_ics.append(pred_ic)
obs_ics.append(obs_ic)
r, p = scatter(pred_ics, obs_ics)
print r, p
def spoof_motifs(motif, num_motifs=10, trials=1, sigma=None,Ne_tol=10**-4,double_sigma=True):
N = len(motif)
L = len(motif[0])
copies = 10*N
if sigma is None:
sigma = sigma_from_matrix(pssm_from_motif(motif,pc=1))
epsilon = (1+double_sigma)*sigma # 15 Jan 2016
print "sigma:", sigma
bio_ic = motif_ic(motif)
def f(Ne):
ps = ps_from_copies(sigma, Ne, L, copies)
motifs = [sample_motif(epsilon, Ne, L, copies, n,ps=ps)
for i in range(trials)]
return mean(map(motif_ic,motifs)) - bio_ic
Ne = log_regress_spec2(f,[1,10],tol=10**-3)
return [sample_motif(sigma, Ne, L, copies, n) for _ in range(num_motifs)]
def extract_motif_object_from_tfdf():
obj = Organism()
genomes = set(tfdf['genome_accession'])
setattr(obj,"tfs",[])
for genome in genomes:
tfs = set(tfdf[tfdf['genome_accession'] == genome]['TF'])
for tf in tfs:
print tf,genome
if not type(tf) is str:
continue
tf_name = genome + "_" + tf
sites = extract_tfdf_sites(genome,tf)
if len(sites) >= 10 and motif_ic(sites) > 5:
setattr(obj,tf_name,sites)
obj.tfs.append(tf_name)
return obj
def rfreq_rseq_experiment(obj,filename="rfreq_vs_rseq_in_sefas_collection.png"):
Rfreqs = []
Rseqs = []
G = 5.0*10**6
min_rfreq = log2(G/500)
for tf in obj.tfs:
motif = getattr(obj,tf)
Rfreqs.append(log(G/len(motif),2))
Rseqs.append(motif_ic(motif))
plt.scatter(Rfreqs,Rseqs)
plt.xlabel("log(G/n) (bits)")
plt.ylabel("Motif Information Content (bits)")
plt.plot([0,20],[0,20],linestyle='--',label='Theory')
plt.plot([min_rfreq,min_rfreq],[0,30],linestyle='--',label='Maximum Plausible Regulon Size')
plt.title("Motif Information Content vs. Search Difficulty")
plt.legend(loc='upper left')
maybesave(filename)
def make_gle_evo_sim_spoofs(bio_motifs, trials_per_motif = 3):
start_time = time.time()
spoofs = []
failures = 0
for it, motif in enumerate(tqdm(bio_motifs, desc='bio_motifs')):
bio_ic = motif_ic(motif)
these_spoofs = [spoof_motif_gle(motif,num_motifs=10, Ne_tol=10**-2)
for i in range(trials_per_motif)]
spoofs.append(these_spoofs)
spoof_ics = map(motif_ic, concat(these_spoofs))
lb, ub = mean_ci(spoof_ics)
out_of_bounds = (not (lb <= bio_ic <= ub))
failures += out_of_bounds
fail_perc = failures/float(it+1)
print it,"bio_ic:", bio_ic, "spoof_ci: (%s,%s)" % (lb, ub), "*" * out_of_bounds,"failures:","%1.2f" % fail_perc
stop_time = time.time()
print "total time:", stop_time - start_time
return spoofs
def results_of_analyze_bio_motifs(results):
# IC
Ls = np.array([len(getattr(Escherichia_coli,tf)[0]) for tf in Escherichia_coli.tfs])
Ls_choose_2 = np.array([choose(L,2) for L in Ls])
bio_ics = np.array([motif_ic(getattr(Escherichia_coli,tf)) for tf in Escherichia_coli.tfs])
sim_ics = np.array([results[tf][0] for tf in Escherichia_coli.tfs])
sim_ic_errs = np.array([1.96*results[tf][1] for tf in Escherichia_coli.tfs])
bio_ics_norm = bio_ics/Ls
sim_ics_norm = sim_ics/Ls
sim_ic_norm_errs = sim_ic_errs/Ls
bio_ginis = np.array([motif_gini(getattr(Escherichia_coli,tf)) for tf in Escherichia_coli.tfs])
sim_ginis = np.array([results[tf][2] for tf in Escherichia_coli.tfs])
sim_gini_errs = np.array([1.96*results[tf][3] for tf in Escherichia_coli.tfs])
bio_mis_norm = np.array([total_motif_mi(getattr(Escherichia_coli,tf))/choose(L,2)
for tf,L in zip(Escherichia_coli.tfs,Ls)])
sim_mis_norm = np.array([results[tf][4]/choose(L,2) for tf,L in zip(Escherichia_coli.tfs,Ls)])
sim_mis_norm_errs = np.array([1.96*results[tf][5]/choose(L,2) for tf,L in zip(Escherichia_coli.tfs,Ls)])
plt.subplot(1,4,1)
plt.errorbar(bio_ics,sim_ics,
yerr=sim_ic_errs,fmt='o')
plt.plot([0,20],[0,20])
plt.xlabel("IC")
plt.subplot(1,4,2)
plt.errorbar(bio_ics_norm,sim_ics_norm,
yerr=sim_ic_norm_errs,fmt='o')
plt.plot([0,2],[0,2])
plt.xlabel("IC/base")
plt.subplot(1,4,3)
plt.errorbar(bio_ginis,sim_ginis,
yerr=sim_gini_errs,fmt='o')
plt.plot([0,1],[0,1])
plt.xlabel("Gini coefficient")
plt.subplot(1,4,4)
plt.errorbar(bio_mis_norm,sim_mis_norm,
yerr=sim_mis_norm_errs,fmt='o')
plt.plot([0,0.5],[0,0.5])
plt.xlabel("MI/pair")
print "IC:", pearsonr(bio_ics, sim_ics)
print "normalized IC:", pearsonr(bio_ics_norm, sim_ics_norm)
print "Gini:", pearsonr(bio_ginis, sim_ginis)
print "normalized MI:", pearsonr(bio_mis_norm, sim_mis_norm)
def tfdf_experiment(replicates=1000,delta_ic=0.1,tolerance=10**-5):
genomes = set(tfdf['genome_accession'])
results_dict = defaultdict(lambda:defaultdict(dict))
for genome_idx,genome in enumerate(genomes):
print "genome:",genome, genome_idx,len(genomes)
tfs = set(tfdf[tfdf['genome_accession'] == genome]['TF'])
for tf_idx,tf in enumerate(tfs):
if not type(tf) is str:
continue
print "tf:",tf,tf_idx,len(tfs)
print genome,tf
bio_motif = extract_tfdf_sites(genome,tf)
if len(bio_motif) < 10:
print "skipping:"
continue
tf_name = genome + "_" + tf
n,L = motif_dimensions(bio_motif)
print "dimensions:",n,L
bio_ic = motif_ic(bio_motif)
bio_gini = motif_gini(bio_motif)
bio_mi = total_motif_mi(bio_motif)
results_dict[tf_name]["bio"]["motif_ic"] = bio_ic
results_dict[tf_name]["bio"]["motif_gini"] = bio_gini
results_dict[tf_name]["bio"]["total_motif_mi"] = bio_mi
correction_per_col = 3/(2*log(2)*n)
desired_ic = bio_ic + L * correction_per_col
t = time.time()
beta = find_beta_for_mean_motif_ic(n,L,desired_ic,tolerance=tolerance)
beta_time = time.time() - t
print "beta, time:",beta, beta_time
print "maxent sampling"
maxent = maxent_motifs_with_ic(n,L,bio_ic,replicates,beta=beta)
print "uniform sampling"
uniform = uniform_motifs_with_ic(n,L,bio_ic,replicates,epsilon=delta_ic,beta=beta)
#print "envelope sampling"
#envelope = envelope_sample_motifs_with_ic(n,L,bio_ic,delta_ic,replicates,beta=beta)
for spoof_name in "maxent uniform".split():
spoofs = eval(spoof_name)
for motif_statname in "motif_ic motif_gini total_motif_mi".split():
print "recording results for:",spoof_name,motif_statname
motif_stat = eval(motif_statname)
results_dict[tf_name][spoof_name][motif_statname] = map(motif_stat,spoofs)
return results_dict
def spoof_motif_ar(motif, num_motifs=10, trials=1, sigma=None,Ne_tol=10**-4):
n = len(motif)
L = len(motif[0])
copies = 10*n
if sigma is None:
sigma = sigma_from_matrix(pssm_from_motif(motif,pc=1))
print "sigma:", sigma
bio_ic = motif_ic(motif)
matrix = sample_matrix(L, sigma)
mu = approx_mu(matrix, copies=10*n, G=5*10**6)
print "mu:", mu
def f(Ne):
motifs = [sample_motif_ar(matrix, mu, Ne, n)
for i in trange(trials)]
return mean(map(motif_ic,motifs)) - bio_ic
x0 = 2
print "Ne guess:", x0
Ne = bisect_interval_noisy(f,x0=x0,iterations=100,lb=1, verbose=False,w=0.5)
print "Ne:",Ne
return [sample_motif_ar(matrix, mu, Ne, n) for _ in trange(num_motifs)]
def Ne_from_motif(bio_motif,interp_rounds,iterations=50000):
"""Given a motif, return Ne that matches mean IC"""
bio_ic = motif_ic(bio_motif)
n = len(bio_motif)
L = len(bio_motif[0])
matrix = [[-ep for ep in row] for row in make_pssm(bio_motif)]
print len(matrix)
def f(Ne,iterations=iterations):
print "Ne",Ne
_,chain = sella_hirsch_mh(matrix=matrix,n=n,Ne=Ne,iterations=iterations,init='ringer')
return mean(map(motif_ic,chain[iterations/2:])) - bio_ic
# lo,hi = 1,5
# data = []
# for _ in xrange(interp_rounds):
# guess = (lo + hi)/2.0
# y = f(guess)
# print lo,hi,guess,y
# data.append((guess,y))
# if y > 0:
# hi = guess
# else:
# lo = guess
# return data
Ne_min = 1
Ne_max = 5
while f(Ne_max) < 0:
print "increasing Ne max"
Ne_max *= 2
xs, ys= transpose([(Ne,f(Ne)) for Ne in np.linspace(Ne_min,Ne_max,interp_rounds)])
# now find an interpolant. We desire smallest sigma of gaussian
# interpolant such that function has at most one inflection point
interp_sigmas = np.linspace(0.01,1,100)
interps = [gaussian_interp(xs,ys,sigma=s) for s in interp_sigmas]
for i,(sigma, interp) in enumerate(zip(interp_sigmas,interps)):
print i,sigma
if num_inflection_points(map(interp,np.linspace(Ne_min,Ne_max,100))) == 1:
"found 1 inflection point"
break
print sigma
Ne = bisect_interval(interp,Ne_min,Ne_max)
return Ne
def moran_process(N=1000,turns=10000,init=sample_species,mutate=mutate,fitness=fitness,pop=None):
if pop is None:
pop = [(lambda spec:(spec,fitness(spec)))(sample_species())
for _ in trange(N)]
hist = []
for turn in xrange(turns):
fits = [f for (s,f) in pop]
#print fits
birth_idx = inverse_cdf_sample(range(N),fits,normalized=False)
death_idx = random.randrange(N)
#print birth_idx,death_idx
mother,f = pop[birth_idx]
daughter = mutate(mother)
#print "mutated"
pop[death_idx] = (daughter,fitness(daughter))
mean_fits = mean(fits)
hist.append((f,mean_fits))
if turn % 10 == 0:
mean_dna_ic = mean([motif_ic(sites,correct=False) for ((sites,eps),_) in pop])
mean_rec_h = mean([h_np(boltzmann(eps)) for ((dna,eps),_) in pop])
print turn,"sel_fit:",f,"mean_fit:",mean_fits,"mean_dna_ic:",mean_dna_ic,"mean_rec_h:",mean_rec_h
return pop
