def get_change_distribution_for_whole_genome(all_data, fitter):
# NOTE: the distribution for all genes should be precomputed by running onset_times_whole_genome.py
filename = join(cache_dir(),fit_results_relative_path(all_data,fitter) + '.pkl')
print 'Loading whole genome onset distribution from {}'.format(filename)
with open(filename) as f:
bin_edges, change_vals = pickle.load(f)
return bin_edges, change_vals
def get_change_distribution_for_whole_genome(all_data, fitter):
# NOTE: the distribution for all genes should be precomputed by running onset_times_whole_genome.py
filename = join(cache_dir(),
fit_results_relative_path(all_data, fitter) + '.pkl')
print 'Loading whole genome onset distribution from {}'.format(filename)
with open(filename) as f:
bin_edges, change_vals = pickle.load(f)
return bin_edges, change_vals
def export_timing_info_for_all_fits(data, fitter, fits):
change_dist = compute_timing_info_for_all_fits(data, fitter, fits)
README = """\
mu:
The mean age of the change distribution for given gene and region.
Dimensions: <n-genes> X <n-regions>
std:
The standard deviation of the change distribution for given gene and region.
Dimensions: <n-genes> X <n-regions>
genes:
Gene names for the genes represented in other arrays
weights:
The change distributions for each gene and region.
Dimensions: <n-genes> X <n-regions> X <n-bins>
bin_centers:
The ages for the center of each bin used in calculating the histogram in "weights".
Dimensions: <n-bins> X 1
bin_edges:
The edges of the bins used in calculating the change histogram.
(centers can be calculated from the bin_edges, but it's convenient to have it pre-calculated)
Dimensions: <n-bins + 1> X 1
regions:
Region names for the regions represented in other arrays
age_scaler:
The scaling used for ages (i.e. 'log' means x' = log(x + 38/52))
"""
mdict = dict(
README_CHANGE_DISTRIBUTIONS=README,
genes=list_of_strings_to_matlab_cell_array(change_dist.genes),
regions=list_of_strings_to_matlab_cell_array(change_dist.regions),
age_scaler=scalers.unify(change_dist.age_scaler).cache_name(),
mu=change_dist.mu,
std=change_dist.std,
bin_edges=change_dist.bin_edges,
bin_centers=change_dist.bin_centers,
weights=change_dist.weights,
)
filename = join(
cache_dir(),
fit_results_relative_path(data, fitter) + '-change-dist.mat')
save_matfile(mdict, filename)
def save_to_mat(self):
filename = join(cache_dir(), 'both', 'dprime-all-pathways-and-regions-{}.mat'.format(self._filename_suffix))
mdict = dict(
pathway = list_of_strings_to_matlab_cell_array([x.pathway for x in self.res]),
r1 = list_of_strings_to_matlab_cell_array([x.r1 for x in self.res]),
r2 = list_of_strings_to_matlab_cell_array([x.r2 for x in self.res]),
score = np.array([x.score for x in self.res]),
delta = np.array([x.delta for x in self.res]),
weighted_delta = np.array([x.weighted_delta for x in self.res]),
mu1_years = np.array([x.mu1_years for x in self.res]),
mu2_years = np.array([x.mu2_years for x in self.res]),
pval = np.array([x.pval for x in self.res]),
pathway_size = np.array([x.pathway_size for x in self.res]),
)
print 'Saving results to {}'.format(filename)
savemat(filename, mdict, oned_as='column')
def export_timing_info_for_all_fits(data, fitter, fits):
change_dist = compute_timing_info_for_all_fits(data, fitter, fits)
README = """\
mu:
The mean age of the change distribution for given gene and region.
Dimensions: <n-genes> X <n-regions>
std:
The standard deviation of the change distribution for given gene and region.
Dimensions: <n-genes> X <n-regions>
genes:
Gene names for the genes represented in other arrays
weights:
The change distributions for each gene and region.
Dimensions: <n-genes> X <n-regions> X <n-bins>
bin_centers:
The ages for the center of each bin used in calculating the histogram in "weights".
Dimensions: <n-bins> X 1
bin_edges:
The edges of the bins used in calculating the change histogram.
(centers can be calculated from the bin_edges, but it's convenient to have it pre-calculated)
Dimensions: <n-bins + 1> X 1
regions:
Region names for the regions represented in other arrays
age_scaler:
The scaling used for ages (i.e. 'log' means x' = log(x + 38/52))
"""
mdict = dict(
README_CHANGE_DISTRIBUTIONS = README,
genes = list_of_strings_to_matlab_cell_array(change_dist.genes),
regions = list_of_strings_to_matlab_cell_array(change_dist.regions),
age_scaler = scalers.unify(change_dist.age_scaler).cache_name(),
mu = change_dist.mu,
std = change_dist.std,
bin_edges = change_dist.bin_edges,
bin_centers = change_dist.bin_centers,
weights = change_dist.weights,
)
filename = join(cache_dir(), fit_results_relative_path(data,fitter) + '-change-dist.mat')
save_matfile(mdict, filename)
def get_onset_times(data, fitter, R2_threshold, b_force=False):
filename = join(cache_dir(),fit_results_relative_path(data,fitter) + '.pkl')
if isfile(filename):
print 'Loading onset distribution from {}'.format(filename)
with open(filename) as f:
bin_edges, change_vals = pickle.load(f)
else:
print 'Computing...'
fits = get_all_fits(data, fitter)
thetas = [fit.theta for fit in iterate_fits(fits, R2_threshold=R2_threshold)]
stages = [stage.scaled(age_scaler) for stage in dev_stages]
low = min(stage.from_age for stage in stages)
high = max(stage.to_age for stage in stages)
bin_edges, change_vals = compute_change_distribution(fitter.shape, thetas, low, high, n_bins=50)
print 'Saving result to {}'.format(filename)
ensure_dir(dirname(filename))
with open(filename,'w') as f:
pickle.dump((bin_edges,change_vals),f)
return bin_edges, change_vals
def save_to_mat(self):
filename = join(
cache_dir(), 'both',
'dprime-all-pathways-and-regions-{}.mat'.format(
self._filename_suffix))
mdict = dict(
pathway=list_of_strings_to_matlab_cell_array(
[x.pathway for x in self.res]),
r1=list_of_strings_to_matlab_cell_array([x.r1 for x in self.res]),
r2=list_of_strings_to_matlab_cell_array([x.r2 for x in self.res]),
score=np.array([x.score for x in self.res]),
delta=np.array([x.delta for x in self.res]),
weighted_delta=np.array([x.weighted_delta for x in self.res]),
mu1_years=np.array([x.mu1_years for x in self.res]),
mu2_years=np.array([x.mu2_years for x in self.res]),
pval=np.array([x.pval for x in self.res]),
pathway_size=np.array([x.pathway_size for x in self.res]),
)
print 'Saving results to {}'.format(filename)
savemat(filename, mdict, oned_as='column')
def save_theta_text_files(data, fitter, fits):
assert fitter.shape.cache_name() == 'spline', "save to text is only supported for splines at the moment"
for dataset in data.datasets:
filename = join(cache_dir(), fit_results_relative_path(dataset,fitter) + '.txt')
dataset_fits = fits[dataset.name]
print 'Saving text file to {}'.format(filename)
with open(filename, 'w') as f:
for (g,r),fit in dataset_fits.iteritems():
if fit.theta is None:
continue
knots, coeffs, degree = fit.theta[0]
knots = list(knots)
coeffs = list(coeffs)
gr_text = """\
Gene symbol: {g}
Region: {r}
Spline knots: {knots}
Spline coefficients: {coeffs}
Spline degree: {degree}
""".format(**locals())
print >>f, gr_text
class SingleRegion(object):
change_dist_filename = join(
cache_dir(), 'both',
'fits-log-all-sigslope-theta-sigslope80-sigma-normal-change-dist.pkl')
def __init__(self, listname='all'):
self.listname = listname
self.pathways = pathway_lists.read_all_pathways(listname)
self.change_dist = load_pickle(
SingleRegion.change_dist_filename,
'change distribution for all genes and regions')
self.genes = self.change_dist.genes
self.regions = self.change_dist.regions
self.g2i = {g: i for i, g in enumerate(self.genes)}
self.r2i = {r: i for i, r in enumerate(self.regions)}
self.age_scaler = self.change_dist.age_scaler
self.mu = self.change_dist.mu
self.std = self.change_dist.std
self.bin_edges = self.change_dist.bin_edges
self.bin_centers = self.change_dist.bin_centers
self.weights = self.change_dist.weights
def region_timings_per_pathway(self):
def mean_age(pathway_genes, r):
pathway_ig = [self.g2i[g] for g in pathway_genes]
ir = self.r2i[r]
ages = self.mu[pathway_ig, ir]
weights = 1 / self.std[pathway_ig, ir]
age = np.dot(weights, ages) / sum(weights)
return self.age_scaler.unscale(age)
res = {} # pathway -> { r -> mu }
for pathway in self.pathways.iterkeys():
pathway_genes = self.pathways[pathway]
res[pathway] = {
r: mean_age(pathway_genes, r)
for r in self.regions
}
return res
def save_theta_text_files(data, fitter, fits):
assert fitter.shape.cache_name(
) == 'spline', "save to text is only supported for splines at the moment"
for dataset in data.datasets:
filename = join(cache_dir(),
fit_results_relative_path(dataset, fitter) + '.txt')
dataset_fits = fits[dataset.name]
print 'Saving text file to {}'.format(filename)
with open(filename, 'w') as f:
for (g, r), fit in dataset_fits.iteritems():
if fit.theta is None:
continue
knots, coeffs, degree = fit.theta[0]
knots = list(knots)
coeffs = list(coeffs)
gr_text = """\
Gene symbol: {g}
Region: {r}
Spline knots: {knots}
Spline coefficients: {coeffs}
Spline degree: {degree}
""".format(**locals())
print >> f, gr_text
def _cache_filename(base_filename, k_of_n):
filename = join(cache_dir(), base_filename + '.pkl')
if k_of_n is not None:
k, n = k_of_n
filename = '{}.{}-of-{}'.format(filename, k, n)
return filename
def _batch_dir(base_filename):
return join(cache_dir(), base_filename + '-batches')
import setup
from os.path import join
import project_dirs
from all_fits import Bunch, convert_format
def f_convert(fit):
"added fitter and shape params"
return Bunch(
fitter=fit.fitter,
seed=fit.seed,
theta=fit.theta,
sigma=fit.sigma,
fit_predictions=fit.fit_predictions,
LOO_predictions=fit.LOO_predictions,
)
filename = join(project_dirs.cache_dir(), 'kang2011',
'fits-serotonin-poly1-t0-s0.pkl')
convert_format(filename, f_convert)
import setup
from os.path import join
import project_dirs
from all_fits import Bunch, convert_format
def f_convert(fit):
"added fitter and shape params"
return Bunch(
fitter = fit.fitter,
seed = fit.seed,
theta = fit.theta,
sigma = fit.sigma,
fit_predictions = fit.fit_predictions,
LOO_predictions = fit.LOO_predictions,
)
filename = join(project_dirs.cache_dir(), 'kang2011', 'fits-serotonin-poly1-t0-s0.pkl')
convert_format(filename, f_convert)
class RegionPairTiming(object):
cube_filename = join(
cache_dir(), 'both',
'fits-log-all-sigslope-theta-sigslope80-sigma-normal-dprime-cube.pkl')
def __init__(self, listname='all'):
self.listname = listname
self.single = SingleRegion(listname)
self.pathways = self.single.pathways
self.genes = self.single.genes
self.regions = self.single.regions
self.g2i = self.single.g2i
self.r2i = self.single.r2i
self.age_scaler = self.single.age_scaler
self.mu = self.single.mu
self.single_std = self.single.std
cube = load_pickle(
RegionPairTiming.cube_filename,
name='timing d-prime info for all genes and region pairs')
self.d_mu = cube.d_mu
self.pair_std = cube.std
self.scores = self.d_mu / self.pair_std
self.baseline = self.baseline_distribution_all_pairs(100, 10000)
@cache(lambda self: join(
cache_dir(), 'both', 'dprime-all-pathways-and-regions-{}.pkl'.format(
self.listname)))
def analyze_all_pathways(self):
res = {} # (pathway,r1,r2) -> timing results
for pathway in self.pathways.iterkeys():
print 'Analyzing region pairs for pathway {}'.format(pathway)
pathway_genes = self.pathways[pathway]
for r1 in self.regions:
for r2 in self.regions:
if r2 <= r1: # keep only results "above the diagonal" (r1 < r2 lexicographically)
continue
pathway_res = self.analyze_pathway_and_region_pair(
pathway_genes, r1, r2)
res[(pathway, r1, r2)] = pathway_res
return TimingResults.fromResultsDct(res, self.listname, self.pathways)
def analyze_pathway_and_region_pair(self, pathway_genes, r1, r2):
ir1, ir2 = self.r2i[r1], self.r2i[r2]
pathway_ig = [self.g2i[g] for g in pathway_genes]
all_pathway_scores = self.scores[pathway_ig, ir1, ir2]
score = nanmean(all_pathway_scores)
mu, sigma = self.baseline[(r1, r2)]
sigma = sigma / np.sqrt(len(pathway_ig))
z = (score - mu) / sigma
pval = z_score_to_p_value(z)
pathway_d_mu = self.d_mu[pathway_ig, ir1, ir2]
pathway_pair_std = self.pair_std[pathway_ig, ir1, ir2]
weights = 1 / pathway_pair_std
valid = ~np.isnan(
pathway_d_mu
) # needed for the PFC region from colantuoni which doesn't contain all genes\
weights, pathway_d_mu = weights[valid], pathway_d_mu[valid]
weighted_delta = np.dot(weights, pathway_d_mu) / sum(weights)
delta = np.mean(pathway_d_mu)
too_many_nans = False
if not valid.all():
assert r1 == 'PFC' or r2 == 'PFC', "r1={}, r2={}".format(r1, r2)
n_genes = len(valid)
n_non_valid = n_genes - np.count_nonzero(valid)
if float(n_non_valid) / n_genes > 0.05:
too_many_nans = True
def mean_age(ir):
if too_many_nans:
return np.NaN
ages = self.mu[pathway_ig, ir]
weights = 1 / self.single_std[pathway_ig, ir]
valid = ~np.isnan(weights)
weights, ages = weights[valid], ages[valid]
age = np.dot(weights, ages) / sum(weights)
return self.age_scaler.unscale(age)
return Bunch(
score=score if not too_many_nans else np.nan,
delta=delta if not too_many_nans else np.nan,
weighted_delta=weighted_delta if not too_many_nans else np.nan,
mu1_years=mean_age(ir1),
mu2_years=mean_age(ir2),
pval=pval if not too_many_nans else np.nan,
pathway_size=len(pathway_genes),
)
@cache(filename=join(cache_dir(), 'both', 'dprime-baseline.pkl'))
def baseline_distribution_all_pairs(self, sample_size, n_samples):
res = {}
for r1 in self.regions:
print 'Sampling baseline distribution of {} vs. all other regions'.format(
r1)
for r2 in self.regions:
if (r2, r1) in res:
mu, sigma = res[(r2, r1)]
res[(r1, r2)] = -mu, sigma
else:
res[(r1, r2)] = self.baseline_distribution_one_pair(
r1, r2, sample_size, n_samples)
return res
def baseline_distribution_one_pair(self, r1, r2, sample_size, n_samples):
ir1, ir2 = self.r2i[r1], self.r2i[r2]
pair_scores = self.scores[:, ir1, ir2]
x = np.empty(n_samples)
for i in xrange(n_samples):
inds = np.random.random_integers(0,
len(pair_scores) - 1, sample_size)
x[i] = nanmean(pair_scores[inds])
mu = x.mean()
sigma = x.std() * np.sqrt(sample_size)
return mu, sigma
def save_as_mat_files(data, fitter, fits, has_change_distributions):
for dataset in data.datasets:
filename = join(cache_dir(), fit_results_relative_path(dataset,fitter) + '.mat')
dataset_fits = fits[dataset.name]
print 'Saving mat file to {}'.format(filename)
shape = fitter.shape
gene_names = dataset.gene_names
gene_idx = {g:i for i,g in enumerate(gene_names)}
n_genes = len(gene_names)
region_names = dataset.region_names
region_idx = {r:i for i,r in enumerate(region_names)}
n_regions = len(region_names)
write_theta = shape.can_export_params_to_matlab()
if write_theta:
theta = init_array(np.NaN, shape.n_params(), n_genes,n_regions)
else:
theta = np.NaN
fit_scores = init_array(np.NaN, n_genes,n_regions)
LOO_scores = init_array(np.NaN, n_genes,n_regions)
fit_predictions = init_array(np.NaN, *dataset.expression.shape)
LOO_predictions = init_array(np.NaN, *dataset.expression.shape)
high_res_predictions = init_array(np.NaN, cfg.n_curve_points_to_plot, n_genes, n_regions)
scaled_high_res_ages = np.linspace(dataset.ages.min(), dataset.ages.max(), cfg.n_curve_points_to_plot)
original_high_res_ages = scalers.unify(dataset.age_scaler).unscale(scaled_high_res_ages)
if has_change_distributions:
change_distribution_bin_centers = fits.change_distribution_params.bin_centers
n_bins = len(change_distribution_bin_centers)
change_distribution_weights = init_array(np.NaN, n_bins, n_genes, n_regions)
else:
change_distribution_bin_centers = []
change_distribution_weights = []
for (g,r),fit in dataset_fits.iteritems():
series = dataset.get_one_series(g,r)
ig = gene_idx[g]
ir = region_idx[r]
fit_scores[ig,ir] = fit.fit_score
LOO_scores[ig,ir] = fit.LOO_score
if write_theta and fit.theta is not None:
theta[:,ig,ir] = fit.theta
if fit.fit_predictions is not None:
fit_predictions[series.original_inds,ig,ir] = fit.fit_predictions
if fit.LOO_predictions is not None:
LOO_predictions[series.original_inds,ig,ir] = fit.LOO_predictions
if fit.theta is not None:
high_res_predictions[:,ig,ir] = shape.f(fit.theta, scaled_high_res_ages)
change_weights = getattr(fit,'change_distribution_weights',None)
if change_weights is not None:
change_distribution_weights[:,ig,ir] = change_weights
mdict = dict(
gene_names = list_of_strings_to_matlab_cell_array(gene_names),
region_names = list_of_strings_to_matlab_cell_array(region_names),
theta = theta,
fit_scores = fit_scores,
LOO_scores = LOO_scores,
fit_predictions = fit_predictions,
LOO_predictions = LOO_predictions,
high_res_predictions = high_res_predictions,
high_res_ages = original_high_res_ages,
change_distribution_bin_centers = change_distribution_bin_centers,
change_distribution_weights = change_distribution_weights,
)
savemat(filename, mdict, oned_as='column')
def _batch_dir(base_filename):
return join(cache_dir(),base_filename + '-batches')
def _cache_filename(base_filename, k_of_n):
filename = join(cache_dir(), base_filename + '.pkl')
if k_of_n is not None:
k,n = k_of_n
filename = '{}.{}-of-{}'.format(filename,k,n)
return filename
for dsname,g,r,fit in iterate_fits(fits, return_keys=True):
weights = calc_bootstrap_change_distribution(shape, fit.theta_samples, bin_edges)
fit.change_distribution_weights = weights
fit.change_distribution_spread = change_distribution_spread_cumsum(bin_centers, weights)
fit.change_distribution_mean_std = change_distribution_mean_and_std(bin_centers, weights)
def calc_bootstrap_change_distribution(shape, theta_samples, bin_edges):
bin_centers = bin_edges_to_centers(bin_edges)
n_params, n_samples = theta_samples.shape
weights = np.zeros(bin_centers.shape)
for i in xrange(n_samples):
weights += calc_change_distribution(shape, theta_samples[:,i], bin_edges)
weights /= n_samples # now values are in fraction of total change (doesn't have to sum up to 1 if ages don't cover the whole transition range)
return weights
@cache(lambda data, fitter, fits: join(cache_dir(), fit_results_relative_path(data,fitter) + '-dprime-cube.pkl'))
def compute_dprime_measures_for_all_pairs(data, fitter, fits):
genes = data.gene_names
regions = data.region_names
r2ds = data.region_to_dataset()
cube_shape = (len(genes), len(regions), len(regions))
d_mu = np.empty(cube_shape) # mu2-mu1 for all genes and region pairs
std = np.empty(cube_shape) # std (combined) for all genes and region pairs
def get_mu_std(g,r):
dsfits = fits[r2ds[r]]
fit = dsfits.get((g,r))
if fit is None:
return np.nan, np.nan
else:
return fit.change_distribution_mean_std
for ig,g in enumerate(genes):
def save_as_mat_files(data, fitter, fits, has_change_distributions):
for dataset in data.datasets:
filename = join(cache_dir(),
fit_results_relative_path(dataset, fitter) + '.mat')
dataset_fits = fits[dataset.name]
print 'Saving mat file to {}'.format(filename)
shape = fitter.shape
gene_names = dataset.gene_names
gene_idx = {g: i for i, g in enumerate(gene_names)}
n_genes = len(gene_names)
region_names = dataset.region_names
region_idx = {r: i for i, r in enumerate(region_names)}
n_regions = len(region_names)
write_theta = shape.can_export_params_to_matlab()
if write_theta:
theta = init_array(np.NaN, shape.n_params(), n_genes, n_regions)
else:
theta = np.NaN
fit_scores = init_array(np.NaN, n_genes, n_regions)
LOO_scores = init_array(np.NaN, n_genes, n_regions)
fit_predictions = init_array(np.NaN, *dataset.expression.shape)
LOO_predictions = init_array(np.NaN, *dataset.expression.shape)
high_res_predictions = init_array(np.NaN, cfg.n_curve_points_to_plot,
n_genes, n_regions)
scaled_high_res_ages = np.linspace(dataset.ages.min(),
dataset.ages.max(),
cfg.n_curve_points_to_plot)
original_high_res_ages = scalers.unify(
dataset.age_scaler).unscale(scaled_high_res_ages)
if has_change_distributions:
change_distribution_bin_centers = fits.change_distribution_params.bin_centers
n_bins = len(change_distribution_bin_centers)
change_distribution_weights = init_array(np.NaN, n_bins, n_genes,
n_regions)
else:
change_distribution_bin_centers = []
change_distribution_weights = []
for (g, r), fit in dataset_fits.iteritems():
series = dataset.get_one_series(g, r)
ig = gene_idx[g]
ir = region_idx[r]
fit_scores[ig, ir] = fit.fit_score
LOO_scores[ig, ir] = fit.LOO_score
if write_theta and fit.theta is not None:
theta[:, ig, ir] = fit.theta
if fit.fit_predictions is not None:
fit_predictions[series.original_inds, ig,
ir] = fit.fit_predictions
if fit.LOO_predictions is not None:
LOO_predictions[series.original_inds, ig,
ir] = fit.LOO_predictions
if fit.theta is not None:
high_res_predictions[:, ig,
ir] = shape.f(fit.theta,
scaled_high_res_ages)
change_weights = getattr(fit, 'change_distribution_weights', None)
if change_weights is not None:
change_distribution_weights[:, ig, ir] = change_weights
mdict = dict(
gene_names=list_of_strings_to_matlab_cell_array(gene_names),
region_names=list_of_strings_to_matlab_cell_array(region_names),
theta=theta,
fit_scores=fit_scores,
LOO_scores=LOO_scores,
fit_predictions=fit_predictions,
LOO_predictions=LOO_predictions,
high_res_predictions=high_res_predictions,
high_res_ages=original_high_res_ages,
change_distribution_bin_centers=change_distribution_bin_centers,
change_distribution_weights=change_distribution_weights,
)
savemat(filename, mdict, oned_as='column')
bin_centers, weights)
def calc_bootstrap_change_distribution(shape, theta_samples, bin_edges):
bin_centers = bin_edges_to_centers(bin_edges)
n_params, n_samples = theta_samples.shape
weights = np.zeros(bin_centers.shape)
for i in xrange(n_samples):
weights += calc_change_distribution(shape, theta_samples[:, i],
bin_edges)
weights /= n_samples # now values are in fraction of total change (doesn't have to sum up to 1 if ages don't cover the whole transition range)
return weights
@cache(lambda data, fitter, fits: join(
cache_dir(),
fit_results_relative_path(data, fitter) + '-dprime-cube.pkl'))
def compute_dprime_measures_for_all_pairs(data, fitter, fits):
genes = data.gene_names
regions = data.region_names
r2ds = data.region_to_dataset()
cube_shape = (len(genes), len(regions), len(regions))
d_mu = np.empty(cube_shape) # mu2-mu1 for all genes and region pairs
std = np.empty(cube_shape) # std (combined) for all genes and region pairs
def get_mu_std(g, r):
dsfits = fits[r2ds[r]]
fit = dsfits.get((g, r))
if fit is None:
return np.nan, np.nan
else:
